We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size , indicative of dephosphorylation , in NFATx1 .

We also show that <protein>calcineurin</protein> associated with the <protein>N-terminal domain</protein> of <protein>NFATx1</protein> at <protein>multiple docking sites</protein> and caused a reduction of size , indicative of dephosphorylation , in <protein>NFATx1</protein> .


We have mapped the inhibitory activity to less than 60 residues , containing motifs that are conserved in all NFAT proteins .

We have mapped the inhibitory activity to less than <protein>60 residues</protein> , containing motifs that are conserved in all <protein>NFAT proteins</protein> .


Finally , we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling .

Finally , we demonstrate that deletion in <protein>NFATx1</protein> of the mapped <protein>60 residues</protein> leads to its nuclear translocation independent of calcium signaling .


Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity .

Our results support the model proposing that the <protein>N-terminal domain</protein> confers calcium-signaling dependence on <protein>NFATx1</protein> transactivation activity by regulating its intracellular localization through a protein module that associates with <protein>calcineurin</protein> and is a target of its <protein>phosphatase</protein> activity .


Neuronal ( type I ) nitric oxide synthase regulates nuclear factor kappaB activity and immunologic ( type II ) nitric oxide synthase expression .

<protein>Neuronal ( type I ) nitric oxide synthase</protein> regulates <protein>nuclear factor kappaB</protein> activity and <protein>immunologic ( type II ) nitric oxide synthase</protein> expression .


Nitric oxide subserves diverse physiologic roles in the nervous system .


NO is produced from at least three different NO synthase ( NOS ) isoforms : neuronal NOS ( nNOS ) , endothelial NOS , and immunologic NOS ( iNOS ) .

NO is produced from at least three different <protein>NO synthase ( NOS ) isoforms</protein> : <protein>neuronal NOS</protein> ( <protein>nNOS</protein> ) , <protein>endothelial NOS</protein> , and <protein>immunologic NOS</protein> ( <protein>iNOS</protein> ) .


We show that nNOS is the predominant isoform constitutively expressed in glia .

We show that <protein>nNOS</protein> is the predominant isoform constitutively expressed in <cell_type>glia</cell_type> .


NO derived from nNOS in glia inhibits the transcription factor nuclear factor kappaB ( NF kappaB ) as NOS inhibitors enhance basal NF kappaB activation .

NO derived from <protein>nNOS</protein> in <cell_type>glia</cell_type> inhibits the <protein>transcription factor</protein> <protein>nuclear factor kappaB</protein> ( <protein>NF kappaB</protein> ) as NOS inhibitors enhance basal <protein>NF kappaB</protein> activation .


Pyrrolidine dithiocarbamate ( PDTC ) is an inhibitor of NF kappaB in most cells ; however , we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC .

Pyrrolidine dithiocarbamate ( PDTC ) is an inhibitor of <protein>NF kappaB</protein> in most cells ; however , we show that PDTC is also a potent scavenger of NO through formation of mononitrosyl iron complexes with PDTC .


In Jurkat cells , a human T-cell lymphoma cell line , tumor necrosis factor-alpha ( TNF-alpha ) induces NF kappaB activation that is inhibited by PDTC .

In <cell_line>Jurkat cells</cell_line> , a human <cell_line>T-cell lymphoma cell line</cell_line> , <protein>tumor necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) induces <protein>NF kappaB</protein> activation that is inhibited by PDTC .


Contrary to the results in Jurkat cells , PDTC did not inhibit tumor necrosis factor-alpha -induced NF kappaB activation in astrocytes ; instead PDTC itself induces NF kappaB activation in astrocytes , and this may be related to scavenging of endogenously produced NO by the PDTC iron complex .

Contrary to the results in <cell_line>Jurkat cells</cell_line> , PDTC did not inhibit <protein>tumor necrosis factor-alpha</protein> -induced <protein>NF kappaB</protein> activation in <cell_type>astrocytes</cell_type> ; instead PDTC itself induces <protein>NF kappaB</protein> activation in <cell_type>astrocytes</cell_type> , and this may be related to scavenging of endogenously produced NO by the PDTC iron complex .


In astrocytes PDTC also dramatically induces the NF kappaB-dependent enzyme , iNOS , supporting the physiologic relevance of endogenous NO regulation of NF kappaB .

In <cell_type>astrocytes</cell_type> PDTC also dramatically induces the <protein>NF kappaB-dependent enzyme</protein> , <protein>iNOS</protein> , supporting the physiologic relevance of endogenous NO regulation of <protein>NF kappaB</protein> .


NF kappaB activation in glia from mice lacking nNOS responds more rapidly to PDTC compared with astrocytes from wild-type mice .

<protein>NF kappaB</protein> activation in <cell_type>glia</cell_type> from mice lacking <protein>nNOS</protein> responds more rapidly to PDTC compared with <cell_type>astrocytes</cell_type> from wild-type mice .


Our data suggest that nNOS in astrocytes regulates NF kappaB activity and iNOS expression , and indicate a novel regulatory role for nNOS in tonically suppressing central nervous system , NF kappaB-regulated genes .

Our data suggest that <protein>nNOS</protein> in <cell_type>astrocytes</cell_type> regulates <protein>NF kappaB</protein> activity and <protein>iNOS</protein> expression , and indicate a novel regulatory role for <protein>nNOS</protein> in tonically suppressing central nervous system , <dna>NF kappaB-regulated genes</dna> .


Involvement of Stat3 in interleukin-6 -induced IgM production in a human B-cell line .

Involvement of <protein>Stat3</protein> in <protein>interleukin-6</protein> -induced <protein>IgM</protein> production in a <cell_line>human B-cell line</cell_line> .


Interleukin-6 ( IL-6 ) is an important B-cell growth and differentiation factor .

<protein>Interleukin-6</protein> ( <protein>IL-6</protein> ) is an important <protein>B-cell growth and differentiation factor</protein> .


IL-6 treatment of the human lymphoblastoid cell line , SKW6.4 , leads to increased IgM production .

<protein>IL-6</protein> treatment of the <cell_line>human lymphoblastoid cell line</cell_line> , <cell_line>SKW6.4</cell_line> , leads to increased <protein>IgM</protein> production .


We have previously shown that IL-6 induces activation of JAK1 and JAK2 in human B cell lines .

We have previously shown that <protein>IL-6</protein> induces activation of <protein>JAK1</protein> and <protein>JAK2</protein> in <cell_line>human B cell lines</cell_line> .


A chimeric IL-6 receptor , comprised of the intracellular tail of the IL-6 receptor subunit gp130 fused to the extracellular domain of the epidermal growth factor ( EGF ) receptor , was stably transfected into SKW6.4 cells .

A chimeric <protein>IL-6 receptor</protein> , comprised of the <protein>intracellular tail</protein> of the <protein>IL-6 receptor subunit</protein> <protein>gp130</protein> fused to the <protein>extracellular domain</protein> of the <protein>epidermal growth factor ( EGF ) receptor</protein> , was stably transfected into <cell_line>SKW6.4 cells</cell_line> .


EGF treatment induced IgM production in cells transfected with an intact gp130 cytoplasmic tail , but not in untransfected cells or cells transfected with a cytoplasmic tail lacking all four signal transducers and activators of transcription ( Stat ) binding sites .

EGF treatment induced <protein>IgM</protein> production in cells transfected with an intact <protein>gp130 cytoplasmic tail</protein> , but not in <cell_line>untransfected cells</cell_line> or cells transfected with a <protein>cytoplasmic tail</protein> lacking all four <protein>signal transducers and activators of transcription ( Stat ) binding sites</protein> .


Moreover , EGF treatment induced Stat3 phosphorylation in cells transfected with the intact chimeric EGF-gp130 receptor along with induction of DNA-mobility shift of a classical interferon-gamma-activated site .

Moreover , EGF treatment induced <protein>Stat3</protein> phosphorylation in cells transfected with the intact <protein>chimeric EGF-gp130 receptor</protein> along with induction of DNA-mobility shift of a <dna>classical interferon-gamma-activated site</dna> .


To define further the relation between Stat3 activation and enhanced IgM production , we determined the effect of chimeric gp130 on the transcriptional activation of a genetic element linked to immunoglobulin production , namely the immunoglobulin heavy chain enhancer ( IgH-enhancer ) .

To define further the relation between <protein>Stat3</protein> activation and enhanced <protein>IgM</protein> production , we determined the effect of chimeric gp130 on the transcriptional activation of a genetic element linked to <protein>immunoglobulin</protein> production , namely the <dna>immunoglobulin heavy chain enhancer</dna> ( <dna>IgH-enhancer</dna> ) .


Parental as well as transfected SKW6.4 cells were transiently transfected with an IgH-enhancer-luciferase construct .

Parental as well as transfected <cell_line>SKW6.4 cells</cell_line> were transiently transfected with an <dna>IgH-enhancer-luciferase construct</dna> .


The transcriptional activity of the IgH-luciferase construct was induced upon ligation of the full-length chimeric receptor but not by truncated gp130 receptors .

The transcriptional activity of the <dna>IgH-luciferase construct</dna> was induced upon ligation of the <protein>full-length chimeric receptor</protein> but not by <protein>truncated gp130 receptors</protein> .


Moreover , the gp130 -induced activity of this reporter gene was abrogated by Stat3EE , a mutant Stat3 incapable of binding DNA .

Moreover , the <protein>gp130</protein> -induced activity of this <dna>reporter gene</dna> was abrogated by <protein>Stat3EE</protein> , a mutant <protein>Stat3</protein> incapable of binding DNA .


These results indicate that IL-6 -induced B-cell differentiation , as measured by IgM production , may be controlled by Stat3 proteins .

These results indicate that <protein>IL-6</protein> -induced B-cell differentiation , as measured by <protein>IgM</protein> production , may be controlled by <protein>Stat3 proteins</protein> .


T-lymphocytes from individuals with filarial inflammatory disease have increased transendothelial migration in vitro .

<cell_type>T-lymphocytes</cell_type> from individuals with filarial inflammatory disease have increased transendothelial migration in vitro .


The in vitro transendothelial migration of circulating filarial antigen-specific T-cells was examined in Wuchereria banerofti infection .

The in vitro transendothelial migration of <cell_type>circulating filarial antigen-specific T-cells</cell_type> was examined in Wuchereria banerofti infection .


Circulating T-cells from individuals with filaria-induced lymphatic pathology ( LP ) had significantly greater migration through unstimulated HUVEC monolayers than did T-cells from asymptomatic infected ( MF ) individuals ( P = 0.04 ) .

<cell_type>Circulating T-cells</cell_type> from individuals with filaria-induced lymphatic pathology ( LP ) had significantly greater migration through unstimulated <cell_type>HUVEC monolayers</cell_type> than did T-cells from asymptomatic infected ( MF ) individuals ( P = 0.04 ) .


In contrast to the MF individuals where no effect was seen , transendothelial migration of 48-hr filarial antigen stimulated T-cells from LP individuals was significantly ( P = 0.01 ) greater than migration of 48-hr media-stimulated T-cells .

In contrast to the MF individuals where no effect was seen , transendothelial migration of 48-hr <cell_type>filarial antigen stimulated T-cells</cell_type> from LP individuals was significantly ( P = 0.01 ) greater than migration of 48-hr <cell_type>media-stimulated T-cells</cell_type> .


In six of seven patients examined , inhibition of the VLA-4/ VCAM-1 pathway resulted in greater than 50 % inhibition of transendothelial migration of T-cells .

In six of seven patients examined , inhibition of the VLA-4/ <protein>VCAM-1</protein> pathway resulted in greater than 50 % inhibition of transendothelial migration of <cell_type>T-cells</cell_type> .


Transcriptional regulation of the ferritin heavy-chain gene : the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation .

Transcriptional regulation of the <dna>ferritin heavy-chain gene</dna> : the activity of the <protein>CCAAT binding factor NF-Y</protein> is modulated in <cell_line>heme-treated Friend leukemia cells</cell_line> and during monocyte-to-macrophage differentiation .


The ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells ( FLCs ) and during monocyte-to-macrophage differentiation .

The <dna>ferritin H-chain gene promoter</dna> regulation was analyzed in <cell_line>heme-treated Friend leukemia cells</cell_line> ( <cell_line>FLCs</cell_line> ) and during monocyte-to-macrophage differentiation .


In the majority of cell lines studied , the regulation of ferritin expression was exerted mostly at the translational level .

In the majority of <cell_line>cell lines</cell_line> studied , the regulation of <protein>ferritin</protein> expression was exerted mostly at the translational level .


However , in differentiating erythroid cells , which must incorporate high levels of iron to sustain hemoglobin synthesis , and in macrophages , which are involved in iron storage , transcriptional regulation seemed to be a relevant mechanism .

However , in <cell_type>differentiating erythroid cells</cell_type> , which must incorporate high levels of iron to sustain <protein>hemoglobin</protein> synthesis , and in <cell_type>macrophages</cell_type> , which are involved in iron storage , transcriptional regulation seemed to be a relevant mechanism .


We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box .

We show here that the minimum region of the <dna>ferritin H-gene promoter</dna> that is able to confer transcriptional regulation by heme in <cell_line>FLCs</cell_line> to a <dna>reporter gene</dna> is <dna>77 nucleotides upstream</dna> of the <dna>TATA box</dna> .


This cis element binds a protein complex referred to as HRF ( heme-responsive factor ) , which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation .

This <dna>cis element</dna> binds a protein complex referred to as <protein>HRF</protein> ( <protein>heme-responsive factor</protein> ) , which is greatly enhanced both in heme-treated <cell_line>FLCs</cell_line> and during monocyte-to-macrophage differentiation .


The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity , since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells .

The <dna>CCAAT element</dna> present in reverse orientation in this promoter region of the <dna>ferritin H-chain gene</dna> is necessary for binding and for gene activity , since a single point mutation is able to abolish the binding of <protein>HRF</protein> and the transcriptional activity in <cell_line>transfected cells</cell_line> .


By competition experiments and supershift assays , we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y .

By competition experiments and supershift assays , we identified the induced <protein>HRF</protein> as containing at least the ubiquitous <protein>transcription factor</protein> <protein>NF-Y</protein> .


NF-Y is formed by three subunits , A , B , and C , all of which are necessary for DNA binding .

<protein>NF-Y</protein> is formed by three <protein>subunits</protein> , <protein>A</protein> , <protein>B</protein> , and <protein>C</protein> , all of which are necessary for DNA binding .


Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme , indicating that NF-Y plays an essential role in this activation .

Cotransfection with a <protein>transdominant negative mutant</protein> of the <protein>NF-YA subunit</protein> abolishes the transcriptional activation by <protein>heme</protein> , indicating that <protein>NF-Y</protein> plays an essential role in this activation .


We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation .

We have also observed a differential expression of the <protein>NF-YA subunit</protein> in heme-treated and control <cell_line>FLCs</cell_line> and during monocyte-to-macrophage differentiation .


Concomitant downregulation of IgH 3 ' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment : implications for dysregulation of translocated c-myc .

Concomitant downregulation of <dna>IgH 3 ' enhancer</dna> activity and <dna>c-myc</dna> expression in a plasmacytoma x fibroblast environment : implications for dysregulation of translocated <dna>c-myc</dna> .


Regulation of immunoglobulin heavy chain ( IgH ) gene expression is controlled by a B cell-specific promoter , intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3 ' end of the IgH locus .

Regulation of <dna>immunoglobulin heavy chain ( IgH ) gene</dna> expression is controlled by a <dna>B cell-specific promoter</dna> , <dna>intronic enhancer</dna> and additional <dna>B cell-specific enhancer elements</dna> identified recently in the 3 ' end of the <dna>IgH locus</dna> .


One of the latter elements , the IgH 3 ' enhancer , is of particular interest : ( 1 ) it is B cell-specific and active only in late B cell development ; ( 2 ) in rodent plasmacytomas and in some human Burkitt 's lymphomas it is part of a locus control region ( LCR ) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus ; and ( 3 ) it has been implicated in the mechanisms that control Ig gene class switch recombination .

One of the latter elements , the <dna>IgH 3 ' enhancer</dna> , is of particular interest : ( 1 ) it is B cell-specific and active only in late B cell development ; ( 2 ) in rodent plasmacytomas and in some human Burkitt 's lymphomas it is part of a <dna>locus control region</dna> ( <dna>LCR</dna> ) that is involved in deregulation of the <dna>c-myc oncogene</dna> as a result of translocation into the <dna>IgH locus</dna> ; and ( 3 ) it has been implicated in the mechanisms that control <dna>Ig gene class</dna> switch recombination .


We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3 ' enhancer .

We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the <dna>IgH 3 ' enhancer</dna> .


When mouse MPC11 plasmacytoma cells , in which the IgH 3 ' enhancer is active , are fused with fibroblasts , Ig expression is extinguished at the level of transcription .

When <cell_line>mouse MPC11 plasmacytoma cells</cell_line> , in which the <dna>IgH 3 ' enhancer</dna> is active , are fused with <cell_type>fibroblasts</cell_type> , Ig expression is extinguished at the level of transcription .


Here we show that in a MPC11 plasmacytoma x fibroblast environment , the IgH 3 ' enhancer is transcriptionally inactive .

Here we show that in a <cell_line>MPC11 plasmacytoma x fibroblast environment</cell_line> , the <dna>IgH 3 ' enhancer</dna> is transcriptionally inactive .


Furthermore , we demonstrate that binding of several B cell-specific transcription factors , essential for IgH 3 ' enhancer activity , is lacking , which may explain 3 ' enhancer inactivity , although the binding of repressors can not be excluded .

Furthermore , we demonstrate that binding of several <protein>B cell-specific transcription factors</protein> , essential for <dna>IgH 3 ' enhancer</dna> activity , is lacking , which may explain 3 ' enhancer inactivity , although the binding of repressors can not be excluded .


Moreover , the high expression level of c-myc , characteristic of the parental MPC11 cells carrying the t ( 12 ; 15 ) translocation , is down-regulated in the hybrids to that in unfused fibroblasts .

Moreover , the high expression level of <dna>c-myc</dna> , characteristic of the parental <cell_line>MPC11 cells</cell_line> carrying the <dna>t ( 12 ; 15 ) translocation</dna> , is down-regulated in the hybrids to that in unfused <cell_type>fibroblasts</cell_type> .


Therefore , inactivation of the IgH 3 ' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer .

Therefore , inactivation of the <dna>IgH 3 ' enhancer</dna> is a multifactorial process affecting several <protein>transcription factors</protein> that control the cell-specific and developmental activity of the <dna>enhancer</dna> .


Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid .

Activation of the <protein>NF-kappaB</protein> <protein>transcription factor</protein> in a <cell_line>T-lymphocytic cell line</cell_line> by hypochlorous acid .


Reactive oxygen species ( ROS ) such as hydrogen peroxide serve as second messengers in the induction of the transcription factor NF-kappaB , and hence in the activation and replication of human immunodeficiency virus type 1 ( HIV-1 ) in human cells .

Reactive oxygen species ( ROS ) such as hydrogen peroxide serve as second messengers in the induction of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> , and hence in the activation and replication of human immunodeficiency virus type 1 ( HIV-1 ) in <cell_type>human cells</cell_type> .


During inflammatory reactions , many oxidative species are produced , one of which is hypochlorous acid ( HOCl ) , which is responsible for the microbicidal effects of activated human polymorphonuclear leukocytes .

During inflammatory reactions , many oxidative species are produced , one of which is hypochlorous acid ( HOCl ) , which is responsible for the microbicidal effects of activated <cell_type>human polymorphonuclear leukocytes</cell_type> .


Treatment of a T-lymphocytic cell line with micromolar concentrations of HOCl promoted the appearance of transcription factor NF-kappaB ( the heterodimer p50/p65 ) in the nucleus of the cells , even in the absence of de novo protein synthesis .

Treatment of a <cell_line>T-lymphocytic cell line</cell_line> with micromolar concentrations of HOCl promoted the appearance of <protein>transcription factor</protein> <protein>NF-kappaB</protein> ( the <protein>heterodimer p50/p65</protein> ) in the nucleus of the cells , even in the absence of de novo protein synthesis .


Western blot analysis of the NF-kappaB inhibitory subunits ( IkappaB ) demonstrated that both IkappaB -alpha proteolysis and p105 processing were induced by the treatment .

Western blot analysis of the <protein>NF-kappaB inhibitory subunits</protein> ( <protein>IkappaB</protein> ) demonstrated that both <protein>IkappaB</protein> -alpha proteolysis and <protein>p105</protein> processing were induced by the treatment .


NF-kappaB activation was very effective when cells were subjected to hyperthermia before being treated with HOCl .

<protein>NF-kappaB</protein> activation was very effective when cells were subjected to hyperthermia before being treated with HOCl .


Various antioxidants , such as pyrrolidine dithiocarbamate , p-bromophenacyl-bromide and nordihydroguaiaretic acid could strongly reduce NF-kappaB translocation , demonstrating the importance of oxidative species in the transduction mechanism .

Various antioxidants , such as pyrrolidine dithiocarbamate , p-bromophenacyl-bromide and nordihydroguaiaretic acid could strongly reduce <protein>NF-kappaB</protein> translocation , demonstrating the importance of oxidative species in the transduction mechanism .


Moreover , ACH-2 cells treated with HOCl or H2O2 released tumour necrosis factor-alpha ( TNF-alpha ) in the supernatants .

Moreover , <cell_line>ACH-2 cells</cell_line> treated with HOCl or H2O2 released <protein>tumour necrosis factor-alpha</protein> ( <protein>TNF-alpha</protein> ) in the supernatants .


The importance of TNF-alpha release in NF-kappaB induction by HOCl or H2O2 was demonstrated by the fact that : ( 1 ) the nuclear appearance of NF-kappaB was promoted in untreated cells ; and ( 2 ) synergism between TNF-alpha and HOCl was detected .

The importance of <protein>TNF-alpha</protein> release in <protein>NF-kappaB</protein> induction by HOCl or H2O2 was demonstrated by the fact that : ( 1 ) the nuclear appearance of <protein>NF-kappaB</protein> was promoted in <cell_line>untreated cells</cell_line> ; and ( 2 ) synergism between <protein>TNF-alpha</protein> and HOCl was detected .


Collectively , these results suggest that HOCl should be considered as an oxidative species capable of inducing NF-kappaB in a T-lymphocytic cell line through a transduction mechanism involving ROS , and having a long-distance effect through subsequent TNF-alpha release .

Collectively , these results suggest that HOCl should be considered as an oxidative species capable of inducing <protein>NF-kappaB</protein> in a <cell_line>T-lymphocytic cell line</cell_line> through a transduction mechanism involving ROS , and having a long-distance effect through subsequent <protein>TNF-alpha</protein> release .


Rapid Ca2+-mediated activation of Rap1 in human platelets .

Rapid Ca2+-mediated activation of <protein>Rap1</protein> in <cell_type>human platelets</cell_type> .


Rap1 is a small , Ras-like GTPase whose function and regulation are still largely unknown .

<protein>Rap1</protein> is a small , <protein>Ras-like GTPase</protein> whose function and regulation are still largely unknown .


We have developed a novel assay to monitor the active , GTP-bound form of Rap1 based on the differential affinity of Rap1GTP and Rap1GDP for the Rap binding domain of RalGDS ( RBD ) .

We have developed a novel assay to monitor the active , <protein>GTP-bound form</protein> of <protein>Rap1</protein> based on the differential affinity of <protein>Rap1GTP</protein> and <protein>Rap1GDP</protein> for the <protein>Rap binding domain</protein> of <protein>RalGDS</protein> ( <protein>RBD</protein> ) .


Stimulation of blood platelets with alpha-thrombin or other platelet activators caused a rapid and strong induction of Rap1 that associated with RBD in vitro .

Stimulation of <cell_type>blood platelets</cell_type> with <protein>alpha-thrombin</protein> or other platelet activators caused a rapid and strong induction of <protein>Rap1</protein> that associated with <protein>RBD</protein> in vitro .


Binding to RBD increased from undetectable levels in resting platelets to > 50 % of total Rap1 within 30 s after stimulation .

Binding to <protein>RBD</protein> increased from undetectable levels in <cell_type>resting platelets</cell_type> to > 50 % of total <protein>Rap1</protein> within 30 s after stimulation .


An increase in the intracellular Ca2+ concentration is both necessary and sufficient for Rap1 activation since it was induced by agents that increase intracellular Ca2+ and inhibited by a Ca2+-chelating agent .

An increase in the intracellular Ca2+ concentration is both necessary and sufficient for <protein>Rap1</protein> activation since it was induced by agents that increase intracellular Ca2+ and inhibited by a Ca2+-chelating agent .


Neither inhibition of translocation of Rap1 to the cytoskeleton nor inhibition of platelet aggregation affected thrombin -induced activation of Rap1 .

Neither inhibition of translocation of <protein>Rap1</protein> to the cytoskeleton nor inhibition of platelet aggregation affected <protein>thrombin</protein> -induced activation of <protein>Rap1</protein> .


In contrast , prostaglandin I2 ( PGI2 ) , a strong negative regulator of platelet function , inhibited agonist-induced as well as Ca2+-induced activation of Rap1 .

In contrast , prostaglandin I2 ( PGI2 ) , a strong negative regulator of <cell_type>platelet</cell_type> function , inhibited agonist-induced as well as Ca2+-induced activation of <protein>Rap1</protein> .


From our results , we conclude that Rap1 activation in platelets is an important common event in early agonist-induced signalling , and that this activation is mediated by an increased intracellular Ca2+ concentration

From our results , we conclude that <protein>Rap1</protein> activation in <cell_type>platelets</cell_type> is an important common event in early agonist-induced signalling , and that this activation is mediated by an increased intracellular Ca2+ concentration


Physical interactions between Ets and NF-kappaB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells .

Physical interactions between <protein>Ets and NF-kappaB/NFAT proteins</protein> play an important role in their cooperative activation of the <dna>human immunodeficiency virus enhancer</dna> in <cell_type>T cells</cell_type> .


The transcriptional regulatory elements of many inducible T-cell genes contain adjacent or overlapping binding sites for the Ets and NF-kappaB/NFAT families of transcription factors .

The <dna>transcriptional regulatory elements</dna> of many <dna>inducible T-cell genes</dna> contain adjacent or <dna>overlapping binding sites</dna> for the <protein>Ets and NF-kappaB/NFAT families</protein> of <protein>transcription factors</protein> .


Similar arrays of functionally important NF-kappaB/NFAT and Ets binding sites are present in the transcriptional enhancers of human immunodeficiency viruses types 1 and 2 ( HIV-1 and HIV-2 ) , suggesting that this pattern of nuclear protein binding sites reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution .

Similar arrays of functionally important <dna>NF-kappaB/NFAT and Ets binding sites</dna> are present in the <dna>transcriptional enhancers</dna> of human immunodeficiency viruses types 1 and 2 ( HIV-1 and HIV-2 ) , suggesting that this pattern of <dna>nuclear protein binding sites</dna> reflects an evolutionarily conserved mechanism for regulating inducible T-cell gene expression that has been co-opted during HIV evolution .


Despite these findings , the molecular mechanisms by which Ets and NF-kappaB/NFAT proteins cooperatively regulate inducible T-cell gene expression remained unknown .

Despite these findings , the molecular mechanisms by which <protein>Ets and NF-kappaB/NFAT proteins</protein> cooperatively regulate inducible T-cell gene expression remained unknown .


In the studies described in this report , we demonstrated a physical interaction between multiple Ets and NF-kappaB/NFAT proteins both in vitro and in activated normal human T cells .

In the studies described in this report , we demonstrated a physical interaction between multiple <protein>Ets and NF-kappaB/NFAT proteins</protein> both in vitro and in <cell_type>activated normal human T cells</cell_type> .


This interaction is mediated by the Ets domain of Ets proteins and the C-terminal region of the Rel homology domains of NF-kappaB/NFAT proteins .

This interaction is mediated by the <dna>Ets domain</dna> of <protein>Ets proteins</protein> and the C-terminal region of the Rel homology domains of <protein>NF-kappaB/NFAT proteins</protein> .


In addition , the Ets - NF-kappaB / NFAT interaction requires the presence of DNA binding sites for both proteins , as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing binding sites for Ets and NF-kappaB proteins .

In addition , the <protein>Ets</protein> - <protein>NF-kappaB</protein> / <protein>NFAT</protein> interaction requires the presence of <dna>DNA binding sites</dna> for both proteins , as it is abolished by the DNA intercalating agents propidium iodide and ethidium bromide and enhanced by the presence of synthetic oligonucleotides containing <dna>binding sites</dna> for <protein>Ets</protein> and <protein>NF-kappaB proteins</protein> .


A dominant-negative mutant of NF-kappaB p50 that binds DNA but fails to interact with Ets proteins inhibits the synergistic activation of the HIV-1 and HIV-2 enhancers by NF-kappaB ( p50 + p65 ) and Ets-1 , suggesting that physical interaction between Ets and NF-kappaB proteins is required for the transcriptional activity of the HIV-1 and HIV-2 enhancers .

A dominant-negative mutant of <protein>NF-kappaB p50</protein> that binds DNA but fails to interact with <protein>Ets proteins</protein> inhibits the synergistic activation of the <dna>HIV-1 and HIV-2 enhancers</dna> by <protein>NF-kappaB</protein> ( <protein>p50</protein> + <protein>p65</protein> ) and <protein>Ets-1</protein> , suggesting that physical interaction between <protein>Ets</protein> and <protein>NF-kappaB proteins</protein> is required for the transcriptional activity of the <dna>HIV-1 and HIV-2 enhancers</dna> .


Taken together , these findings suggest that evolutionarily conserved physical interactions between Ets and NF-kappaB/NFAT proteins are important in regulating the inducible expression of T-cell genes and viruses .

Taken together , these findings suggest that evolutionarily conserved physical interactions between <protein>Ets and NF-kappaB/NFAT proteins</protein> are important in regulating the inducible expression of <dna>T-cell genes</dna> and viruses .


These interactions represent a potential target for the development of novel immunosuppressive and antiviral therapies .


An acute myeloid leukemia gene , AML1 , regulates transcriptional activation and hemopoietic myeloid cell differentiation antagonistically by two alternative spliced forms .

An <dna>acute myeloid leukemia gene</dna> , <dna>AML1</dna> , regulates transcriptional activation and hemopoietic myeloid cell differentiation antagonistically by two alternative spliced forms .


The AML1 gene on chromosome 21 is disrupted in the ( 8 ; 21 ) ( q22 ; q22 ) and ( 3 ; 21 ) ( q26 ; q22 ) translocations associated with myelogenous leukemias and encodes a DNA-binding protein .

The <dna>AML1 gene</dna> on <dna>chromosome 21</dna> is disrupted in the <dna>( 8 ; 21 ) ( q22 ; q22 ) and ( 3 ; 21 ) ( q26 ; q22 ) translocations</dna> associated with myelogenous leukemias and encodes a <protein>DNA-binding protein</protein> .


From AML1 gene , two representative forms of proteins , AML1a and AML1b , are produced by an alternative splicing .

From <dna>AML1 gene</dna> , two representative forms of proteins , <protein>AML1a</protein> and <protein>AML1b</protein> , are produced by an alternative splicing .


Both forms have DNA-binding domain , but AML1a lacks a putative transcriptional activation domain which AML1b has .

Both forms have <protein>DNA-binding domain</protein> , but <protein>AML1a</protein> lacks a putative transcriptional activation domain which <protein>AML1b</protein> has .


Here we demonstrate that AML1a , which solely has no effects as a transcriptional regulator , dominantly suppresses transcriptional activation by AML1b , and that AML1a exhibits the higher affinity for DNA-binding than AML1b .

Here we demonstrate that <protein>AML1a</protein> , which solely has no effects as a transcriptional regulator , dominantly suppresses transcriptional activation by <protein>AML1b</protein> , and that <protein>AML1a</protein> exhibits the higher affinity for DNA-binding than <protein>AML1b</protein> .


Furthermore a dominant negative form of AML1 , AML1a , totally suppressed granulocytic differentiation otherwise induced by granulocyte colony-stimulating factor when AML1a was overexpressed in 32Dc13 murine myeloid cells .

Furthermore a <protein>dominant negative form</protein> of <protein>AML1</protein> , <protein>AML1a</protein> , totally suppressed granulocytic differentiation otherwise induced by <protein>granulocyte colony-stimulating factor</protein> when <protein>AML1a</protein> was overexpressed in <cell_type>32Dc13 murine myeloid cells</cell_type> .


Such differentiation block by AML1a was canceled by the concomitant overexpression of AML1b .

Such differentiation block by <protein>AML1a</protein> was canceled by the concomitant overexpression of <protein>AML1b</protein> .


These data strongly suggest that a transcriptionally active form of AML1 is essential for the myeloid cell differentiation .

These data strongly suggest that a transcriptionally active form of <protein>AML1</protein> is essential for the myeloid cell differentiation .


In addition , we observed an altered expression level of AML1 along with the myeloid differentiation in several hemopoietic cell lines .

In addition , we observed an altered expression level of <protein>AML1</protein> along with the myeloid differentiation in several <cell_line>hemopoietic cell lines</cell_line> .


In these cases , at least , the AML1 expression level is a potential regulator for myeloid cell differentiation .

In these cases , at least , the <protein>AML1</protein> expression level is a potential regulator for myeloid cell differentiation .


Nuclear factor-kappa B potently up-regulates the promoter activity of RANTES , a chemokine that blocks HIV infection .

<protein>Nuclear factor-kappa B</protein> potently up-regulates the promoter activity of <protein>RANTES</protein> , a chemokine that blocks HIV infection .


The complex network of cytokines that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection .

The complex network of <protein>cytokines</protein> that are involved in inflammatory and immunoregulatory responses plays a critical role in the pathogenesis of HIV infection .


RANTES ( regulated upon activation , normal T cell expressed and secreted ) is a cytokine that belongs to the beta-chemokine family ; it is chemoattractant for CD4+/CD45RO T cells , it is produced by various cell types including CD8+ and CD4+ T cells as well as monocytes/macrophages , and has recently been shown to suppress replication of macrophage-tropic strains of HIV in CD4+ T cells .

<protein>RANTES</protein> ( <protein>regulated upon activation , normal T cell expressed and secreted</protein> ) is a <protein>cytokine</protein> that belongs to the <protein>beta-chemokine family</protein> ; it is chemoattractant for <cell_type>CD4+/CD45RO T cells</cell_type> , it is produced by various cell types including <cell_type>CD8+ and CD4+ T cells</cell_type> as well as <cell_type>monocytes/macrophages</cell_type> , and has recently been shown to suppress replication of macrophage-tropic strains of HIV in <cell_type>CD4+ T cells</cell_type> .


To investigate the molecular mechanisms of RANTES expression , the RANTES promoter region was analyzed by transient expression and gel-mobility shift assays .

To investigate the molecular mechanisms of <protein>RANTES</protein> expression , the <dna>RANTES promoter region</dna> was analyzed by transient expression and gel-mobility shift assays .


We demonstrate that : 1 ) RANTES promoter activity is up-regulated by PMA plus ionomycin , coexpression of the p65 subunit of nuclear factor ( NF ) -kappa B , the proinflammatory cytokines TNF-alpha and IL-1 beta , and the CD28 costimulatory pathway ; 2 ) the RANTES promoter region contains four NF-kappa B binding sites at positions -30 , -44 , -213 , and -579 relative to the transcription start site ; 3 ) one site ( -213 ) is an NF-AT ( nuclear factor of activated T cells ) binding site that also has weak affinity to NF-kappa B , and the most distal site ( -579 ) also serves as a CD28-responsive element ; and 4 ) mutation on any of those NF-kappa B sites or coexpression of I kappa B alpha ( cytoplasmic inhibitor of NF-kappa B ) markedly reduced the promoter activity .

We demonstrate that : 1 ) <protein>RANTES</protein> promoter activity is up-regulated by PMA plus ionomycin , coexpression of the <protein>p65 subunit</protein> of <protein>nuclear factor ( NF ) -kappa B</protein> , the <protein>proinflammatory cytokines</protein> <protein>TNF-alpha</protein> and <protein>IL-1 beta</protein> , and the <protein>CD28</protein> costimulatory pathway ; 2 ) the <dna>RANTES promoter region</dna> contains four <dna>NF-kappa B binding sites</dna> at <dna>positions -30 , -44 , -213 , and -579</dna> relative to the <dna>transcription start site</dna> ; 3 ) one site ( -213 ) is an <dna>NF-AT ( nuclear factor of activated T cells ) binding site</dna> that also has weak affinity to <protein>NF-kappa B</protein> , and the most distal site ( -579 ) also serves as a <dna>CD28-responsive element</dna> ; and 4 ) mutation on any of those <dna>NF-kappa B sites</dna> or coexpression of <protein>I kappa B alpha</protein> ( <protein>cytoplasmic inhibitor of NF-kappa B</protein> ) markedly reduced the promoter activity .


Thus , NF-kappa B , a potent transcriptional activator of HIV expression , is also involved in the expression of RANTES , a chemokine that blocks infection by macrophage-tropic strains of HIV .

Thus , <protein>NF-kappa B</protein> , a potent transcriptional activator of HIV expression , is also involved in the expression of <protein>RANTES</protein> , a <protein>chemokine</protein> that blocks infection by macrophage-tropic strains of HIV .


Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3 -mediated survival of pro-B lymphocytes .

Pivotal role for the <protein>NFIL3/E4BP4 transcription factor</protein> in <protein>interleukin 3</protein> -mediated survival of <cell_type>pro-B lymphocytes</cell_type> .


The E2A-HLF ( hepatic leukemia factor ) oncoprotein , generated in pro-B lymphocytes by fusion of the trans-activation domain of E2A to the basic region/leucine zipper ( bZIP ) domain of HLF , functions as an anti-apoptotic transcription factor in leukemic cell transformation .

The <protein>E2A-HLF ( hepatic leukemia factor ) oncoprotein</protein> , generated in <cell_type>pro-B lymphocytes</cell_type> by fusion of the <protein>trans-activation domain</protein> of <protein>E2A</protein> to the <protein>basic region/leucine zipper ( bZIP ) domain</protein> of <protein>HLF</protein> , functions as an <protein>anti-apoptotic transcription factor</protein> in leukemic cell transformation .


When introduced into interleukin 3 ( IL-3 ) -dependent mouse pro-B lymphocytes , E2A-HLF prevents apoptosis induced by growth factor deprivation , suggesting that IL-3 mediates cell survival through activation of a transcription factor whose activity can be constitutively replaced by the chimeric oncoprotein .

When introduced into <protein>interleukin 3</protein> ( <protein>IL-3</protein> ) -dependent mouse <cell_type>pro-B lymphocytes</cell_type> , <protein>E2A-HLF</protein> prevents apoptosis induced by <protein>growth factor</protein> deprivation , suggesting that <protein>IL-3</protein> mediates cell survival through activation of a <protein>transcription factor</protein> whose activity can be constitutively replaced by the <protein>chimeric oncoprotein</protein> .


We considered four bZIP transcription factors as candidates for this putative IL-3-regulated factor , each of which binds avidly to the DNA consensus sequence recognized by E2A-HLF and is related to the Caenorhabditis elegans CES-2 ( cell death specification protein ) neuron-specific mediator of cell death .

We considered four <protein>bZIP transcription factors</protein> as candidates for this putative <protein>IL-3-regulated factor</protein> , each of which binds avidly to the <dna>DNA consensus sequence</dna> recognized by <protein>E2A-HLF</protein> and is related to the <protein>Caenorhabditis elegans CES-2</protein> ( <protein>cell death specification protein</protein> ) <protein>neuron-specific mediator of cell death</protein> .


The expression and binding activity of the Nfil3 protein ( also called E4bp4 ) , but not of Hlf , Dbp , or Tef , was found to be regulated by IL-3 in mouse pro-B cell lines ( Baf-3 and FL5.12 ) .

The expression and binding activity of the <protein>Nfil3 protein</protein> ( also called <protein>E4bp4</protein> ) , but not of <protein>Hlf</protein> , <protein>Dbp</protein> , or <protein>Tef</protein> , was found to be regulated by <protein>IL-3</protein> in <cell_line>mouse pro-B cell lines</cell_line> ( <cell_line>Baf-3</cell_line> and <cell_line>FL5.12</cell_line> ) .


Northern blot analysis showed that Nfil3/E4bp4 is regulated as a `` delayed-early '' IL-3-responsive gene , requiring de novo protein synthesis .

Northern blot analysis showed that <protein>Nfil3/E4bp4</protein> is regulated as a <dna>`` delayed-early '' IL-3-responsive gene</dna> , requiring de novo protein synthesis .


In the absence of IL-3 , enforced expression of the human NFIL3/E4BP4 cDNA promoted the survival but not the growth of IL-3-dependent pro-B cells .

In the absence of <protein>IL-3</protein> , enforced expression of the <dna>human NFIL3/E4BP4 cDNA</dna> promoted the survival but not the growth of <cell_type>IL-3-dependent pro-B cells</cell_type> .


Our results implicate NFIL3/E4BP4 ( nuclear factor regulated by IL-3/adenovirus E4 promoter binding protein ) in a distinct growth factor-regulated signaling pathway that is responsible for the survival of early B-cell progenitors , and whose alteration by E2A-HLF leads to childhood B lineage leukemia .

Our results implicate <protein>NFIL3/E4BP4</protein> ( <protein>nuclear factor regulated by IL-3/adenovirus E4 promoter binding protein</protein> ) in a distinct growth factor-regulated signaling pathway that is responsible for the survival of <cell_type>early B-cell progenitors</cell_type> , and whose alteration by <protein>E2A-HLF</protein> leads to childhood B lineage leukemia .


Detection of adenovirus DNA in peripheral blood mononuclear cells by polymerase chain reaction assay .

Detection of adenovirus DNA in <cell_type>peripheral blood mononuclear cells</cell_type> by polymerase chain reaction assay .


Adenovirus can establish persistent infections which may reactivate and cause disease in immunocompromised hosts .


Lymphocytes have been postulated to serve as a site of adenoviral persistence based upon the ability to isolate adenovirus from tonsils and to detect adenovirus DNA by Southern blot hybridization in peripheral blood mononuclear cells ( PBMC ) .

<cell_type>Lymphocytes</cell_type> have been postulated to serve as a site of adenoviral persistence based upon the ability to isolate adenovirus from tonsils and to detect adenovirus DNA by Southern blot hybridization in <cell_type>peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMC</cell_type> ) .


To test this hypothesis , a more sensitive and specific polymerase chain reaction ( PCR ) assay was developed to detect adenovirus DNA .


Two sets of nested primers were designed to conserved sequences in the adenovirus E1A and hexon genes .

Two sets of nested primers were designed to conserved sequences in the <dna>adenovirus E1A and hexon genes</dna> .


The E1A and hexon primers amplified DNA from representative adenoviral serotypes in all six adenoviral groups ( A-F ) .

The <dna>E1A and hexon primers</dna> amplified DNA from representative adenoviral serotypes in all six adenoviral groups ( A-F ) .


Both primers detected a single copy of the adenovirus type 2 genome but were less sensitive for the group B type 35 .

Both primers detected a single copy of the <dna>adenovirus type 2 genome</dna> but were less sensitive for the group B type 35 .


of 33 PBMC specimens from healthy adults and only one of 40 pediatric samples was positive ( at a low level ) for adenovirus DNA by nested PCR assay .

of 33 <cell_type>PBMC specimens</cell_type> from healthy adults and only one of 40 pediatric samples was positive ( at a low level ) for adenovirus DNA by nested PCR assay .


In comparison , PBMC from two children with fatal adenoviral infection were both strongly positive for adenovirus DNA .

In comparison , <cell_type>PBMC</cell_type> from two children with fatal adenoviral infection were both strongly positive for adenovirus DNA .


It is concluded that , in contrast to a previous study , PBMC are not a common site of persistent group C adenoviral infection .

It is concluded that , in contrast to a previous study , <cell_type>PBMC</cell_type> are not a common site of persistent group C adenoviral infection .


In addition , assay of PBMC by the adenovirus-specific PCR may help detect early invasive disease and warrants further evaluation .

In addition , assay of <cell_type>PBMC</cell_type> by the adenovirus-specific PCR may help detect early invasive disease and warrants further evaluation .


Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP .

Common and distinct intracellular signaling pathways in <cell_type>human neutrophils</cell_type> utilized by <protein>platelet activating factor</protein> and <protein>FMLP</protein> .


Stimulation of human neutrophils with chemoattractants FMLP or platelet activating factor ( PAF ) results in different but overlapping functional responses .

Stimulation of <cell_type>human neutrophils</cell_type> with <protein>chemoattractants</protein> <protein>FMLP</protein> or <protein>platelet activating factor</protein> ( <protein>PAF</protein> ) results in different but overlapping functional responses .


We questioned whether these differences might reflect patterns of intracellular signal transduction .


Stimulation with either PAF or FMLP resulted in equivalent phosphorylation and activation of the mitogen-activated protein kinase ( MAPk ) homologue 38-kD murine MAP kinase homologous to HOG-1 ( p38 ) MAPk .

Stimulation with either <protein>PAF</protein> or <protein>FMLP</protein> resulted in equivalent phosphorylation and activation of the <protein>mitogen-activated protein kinase ( MAPk ) homologue</protein> <protein>38-kD murine MAP kinase</protein> homologous to <protein>HOG-1 ( p38 ) MAPk</protein> .


Neither FMLP nor PAF activated c-jun NH2-terminal MAPk ( JNKs ) .

Neither <protein>FMLP</protein> nor <protein>PAF</protein> activated <protein>c-jun NH2-terminal MAPk</protein> ( <protein>JNKs</protein> ) .


Under identical conditions , FMLP but not PAF , resulted in significant p42/44 ( ERK ) MAPk activation .

Under identical conditions , <protein>FMLP</protein> but not <protein>PAF</protein> , resulted in significant <protein>p42/44 ( ERK ) MAPk</protein> activation .


Both FMLP and PAF activated MAP kinase kinase-3 ( MKK3 ) , a known activator of p38 MAPk .

Both <protein>FMLP</protein> and <protein>PAF activated MAP kinase kinase-3</protein> ( <protein>MKK3</protein> ) , a known activator of <protein>p38 MAPk</protein> .


Both MAP ERK kinase kinase-1 ( MEKK1 ) and Raf are activated strongly by FMLP , but minimally by PAF .

Both <protein>MAP ERK kinase kinase-1</protein> ( <protein>MEKK1</protein> ) and <protein>Raf</protein> are activated strongly by <protein>FMLP</protein> , but minimally by <protein>PAF</protein> .


Pertussis toxin blocked FMLP -induced activation of the p42/44 ( ERK ) MAPk cascade , but not that of p38 MAPk .

<protein>Pertussis toxin</protein> blocked <protein>FMLP</protein> -induced activation of the <protein>p42/44 ( ERK ) MAPk</protein> cascade , but not that of <protein>p38 MAPk</protein> .


A specific p38 MAPk inhibitor ( SK & F 86002 ) blocked superoxide anion production in response to FMLP and reduced adhesion and chemotaxis in response to PAF or FMLP .

A specific <protein>p38 MAPk</protein> inhibitor ( SK & F 86002 ) blocked superoxide anion production in response to <protein>FMLP</protein> and reduced adhesion and chemotaxis in response to <protein>PAF</protein> or <protein>FMLP</protein> .


These results demonstrate distinct patterns of intracellular signaling for two chemoattractants and suggest that selective activation of intracellular signaling cascades may underlie different patterns of functional responses .

These results demonstrate distinct patterns of intracellular signaling for two <protein>chemoattractants</protein> and suggest that selective activation of intracellular signaling cascades may underlie different patterns of functional responses .


Cloning of the novel human myeloid-cell-specific C/EBP-epsilon transcription factor .

Cloning of the <protein>novel human myeloid-cell-specific C/EBP-epsilon transcription factor</protein> .


Chicken NF-M transcription factor , in cooperation with either c-Myb or v-Myb , is active in the combinatorial activation of myeloid-cell-specific genes in heterologous cell types , such as embryonic fibroblasts .

<protein>Chicken NF-M transcription factor</protein> , in cooperation with either <protein>c-Myb</protein> or <protein>v-Myb</protein> , is active in the combinatorial activation of <dna>myeloid-cell-specific genes</dna> in <cell_type>heterologous cell types</cell_type> , such as <cell_type>embryonic fibroblasts</cell_type> .


In humans , similar effects were observed with homologous members of the CCAAT/enhancer-binding protein ( C/EBP ) family of transcriptional regulators , especially the human homolog of chicken NF-M , C/EBP-beta ( NF-IL6 ) .

In humans , similar effects were observed with homologous members of the <protein>CCAAT/enhancer-binding protein ( C/EBP ) family</protein> of <protein>transcriptional regulators</protein> , especially the human homolog of <protein>chicken NF-M</protein> , <protein>C/EBP-beta</protein> ( <protein>NF-IL6</protein> ) .


However , the NF-IL6 gene is expressed in a variety of nonmyeloid cell types and is strongly inducible in response to inflammatory stimuli , making it an unlikely candidate to have an exclusive role as a combinatorial differentiation switch during myelopoiesis in human cells .

However , the <dna>NF-IL6 gene</dna> is expressed in a variety of nonmyeloid cell types and is strongly inducible in response to inflammatory stimuli , making it an unlikely candidate to have an exclusive role as a combinatorial differentiation switch during myelopoiesis in <cell_type>human cells</cell_type> .


By using a reverse transcription-PCR-based approach and a set of primers specific for the DNA-binding domains of highly homologous members of the C/EBP family of transcriptional regulators , we have cloned a novel human gene encoding a member of the C/EBP gene family , identified as the human homolog of CRP1 , C/EBP-epsilon .

By using a reverse transcription-PCR-based approach and a set of primers specific for the <dna>DNA-binding domains</dna> of highly homologous members of the <protein>C/EBP family</protein> of <protein>transcriptional regulators</protein> , we have cloned a <dna>novel human gene</dna> encoding a member of the <dna>C/EBP gene family</dna> , identified as the human homolog of <protein>CRP1</protein> , <protein>C/EBP-epsilon</protein> .


A 1.2-kb cDNA encoding full-length human C/EBP-epsilon was cloned from a promyelocyte-late myeloblast-derived lambda gt11 library .

A <dna>1.2-kb cDNA</dna> encoding full-length <dna>human C/EBP-epsilon</dna> was cloned from a <dna>promyelocyte-late myeloblast-derived lambda gt11 library</dna> .


Molecular analysis of the cDNA and genomic clones indicated the presence of two exons encoding a protein with an apparent molecular mass of 32 kDa and a pI of 9.5 .

Molecular analysis of the cDNA and genomic clones indicated the presence of two <dna>exons</dna> encoding a protein with an apparent molecular mass of 32 kDa and a pI of 9.5 .


Primer extension analysis of C/EBP-epsilon mRNA detected a single major transcription start site approximately 200 bp upstream of the start codon .

Primer extension analysis of <rna>C/EBP-epsilon mRNA</rna> detected a single major <dna>transcription start site</dna> approximately 200 bp upstream of the <dna>start codon</dna> .


The putative promoter area is similar to those of several other myeloid-cell-specific genes in that it contains no TATAAA box but has a number of purine-rich stretches with multiple sites for the factors of the Ets family of transcriptional regulators .

The putative promoter area is similar to those of several other myeloid-cell-specific genes in that it contains no <dna>TATAAA box</dna> but has a number of <dna>purine-rich stretches</dna> with multiple sites for the factors of the <protein>Ets family</protein> of <protein>transcriptional regulators</protein> .


Northern blot analyses indicated a highly restricted mRNA expression pattern , with the strongest expression occurring in promyelocyte and late-myeloblast-like cell lines .

Northern blot analyses indicated a highly restricted mRNA expression pattern , with the strongest expression occurring in <cell_line>promyelocyte and late-myeloblast-like cell lines</cell_line> .


Western blot and immunoprecipitation studies using rabbit anti-C/EBP-epsilon antibodies raised against the N-terminal portion of C/EBP-epsilon ( amino acids 1 to 115 ) showed that C/EBP-epsilon is a 32-kDa nuclear phosphoprotein .

Western blot and immunoprecipitation studies using <protein>rabbit anti-C/EBP-epsilon antibodies</protein> raised against the <protein>N-terminal portion</protein> of <protein>C/EBP-epsilon</protein> ( <protein>amino acids 1 to 115</protein> ) showed that <protein>C/EBP-epsilon</protein> is a <protein>32-kDa nuclear phosphoprotein</protein> .


The human C/EBP-epsilon protein exhibited strong and specific binding to double-stranded DNA containing consensus C/EBP sites .

The human <protein>C/EBP-epsilon</protein> protein exhibited strong and specific binding to <dna>double-stranded DNA containing consensus C/EBP sites</dna> .


Cotransfection of the C/EBP-epsilon sense and antisense expression constructs together with chloramphenicol acetyltransferase reporter vectors containing myeloid-cell-specific c-mim and human myeloperoxidase promoters suggested a role for C/EBP-epsilon transcription factor in the regulation of a subset of myeloid-cell-specific genes .

Cotransfection of the <protein>C/EBP-epsilon</protein> sense and antisense expression constructs together with <dna>chloramphenicol acetyltransferase reporter vectors</dna> containing <dna>myeloid-cell-specific c-mim and human myeloperoxidase promoters</dna> suggested a role for <protein>C/EBP-epsilon</protein> <protein>transcription factor</protein> in the regulation of a subset of <dna>myeloid-cell-specific genes</dna> .


Transient tranfection of a promyelocyte cell line ( NB4 ) with a C/EBP-epsilon expression plasmid increased cell growth by sevenfold , while antisense C/EBP-epsilon caused a fivefold decrease in clonal growth of these cells .

Transient tranfection of a <cell_line>promyelocyte cell line</cell_line> ( <cell_line>NB4</cell_line> ) with a <dna>C/EBP-epsilon expression plasmid</dna> increased cell growth by sevenfold , while antisense <protein>C/EBP-epsilon</protein> caused a fivefold decrease in clonal growth of these cells .


The tumour associated cell surface antigen A6H is costimulatory for human CD4+ but not CD8+ T cells .

The <protein>tumour associated cell surface antigen</protein> <protein>A6H</protein> is costimulatory for <cell_type>human CD4+ but not CD8+ T cells</cell_type> .


The A6H monoclonal antibody ( mAb ) recognizes a 120 , 000-140 , 000 MW antigen that is expressed at similar densities on 85-90 % of human CD4+ and CD8+ T cells and on renal cell carcinomas .

The <protein>A6H monoclonal antibody</protein> ( mAb ) recognizes a <protein>120 , 000-140 , 000 MW antigen</protein> that is expressed at similar densities on 85-90 % of human <cell_type>CD4+ and CD8+ T cells</cell_type> and on renal cell carcinomas .


The binding of the A6H mAb induced a costimulatory signal in anti-CD3 activated T cells .

The binding of the <protein>A6H mAb</protein> induced a costimulatory signal in <cell_line>anti-CD3 activated T cells</cell_line> .


In the present report , we show that A6H costimulated cell proliferation and cytokine production in purified CD4+ T cells .

In the present report , we show that <protein>A6H</protein> costimulated cell proliferation and <protein>cytokine</protein> production in purified <cell_type>CD4+ T cells</cell_type> .


Unexpectedly , the CD8+ T-cell subpopulation failed to respond .

Unexpectedly , the <cell_type>CD8+ T-cell subpopulation</cell_type> failed to respond .


CD4+ T cells costimulated with the A6H mAb upregulated CD80 , CD86 , CD71 , interleukin-2 ( IL-2 ) R alpha , IL-2R beta and IL-2R gamma , while no corresponding up-regulation of these cell surface molecules was seen in CD8+ T cells .

<cell_type>CD4+ T cells</cell_type> costimulated with the <protein>A6H mAb</protein> upregulated <protein>CD80</protein> , <protein>CD86</protein> , <protein>CD71</protein> , <protein>interleukin-2 ( IL-2 ) R alpha</protein> , <protein>IL-2R beta</protein> and <protein>IL-2R gamma</protein> , while no corresponding up-regulation of these <protein>cell surface molecules</protein> was seen in <cell_type>CD8+ T cells</cell_type> .


In order to investigate the nature of the A6H mAb costimulus at the transcriptional level we have examined induction of the transcription factors OCT-1 , AP-1 and NF-kappa B which are known to be transcriptional regulators of several cytokine and cytokine receptor genes , including the IL-2 and IL-2R genes .

In order to investigate the nature of the <protein>A6H mAb</protein> costimulus at the transcriptional level we have examined induction of the <protein>transcription factors</protein> <protein>OCT-1</protein> , <protein>AP-1</protein> and <protein>NF-kappa B</protein> which are known to be <protein>transcriptional regulators</protein> of several <protein>cytokine</protein> and <protein>cytokine</protein> receptor genes , including the <dna>IL-2 and IL-2R genes</dna> .


Co-ligation of the A6H antigen and the CD3 complex induced expression of the transcription factor AP-1 in CD4+ T cells , whereas no increase in NF-kappa B and octamer-binding ( Oct ) proteins was seen compared to T cells stimulated with anti-CD3 alone .

Co-ligation of the <protein>A6H</protein> antigen and the <protein>CD3 complex</protein> induced expression of the <protein>transcription factor</protein> <protein>AP-1</protein> in <cell_type>CD4+ T cells</cell_type> , whereas no increase in <protein>NF-kappa B</protein> and <protein>octamer-binding ( Oct ) proteins</protein> was seen compared to <cell_type>T cells</cell_type> stimulated with <protein>anti-CD3</protein> alone .


Furthermore , no induction of AP-1 was seen in A6H costimulated CD8+ T cells .

Furthermore , no induction of <protein>AP-1</protein> was seen in <protein>A6H</protein> costimulated <cell_type>CD8+ T cells</cell_type> .


These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to A6H ligation .

These results suggests that both proximal steps in CD8+ T-cell activation as well as the later phases are unresponsive to <protein>A6H</protein> ligation .


Molecular differences of the A6H molecule or distinct regulation of the A6H transduced AP-1 activation pathway may exist in CD4+ and CD8+ T cell subpopulations .

Molecular differences of the <protein>A6H molecule</protein> or distinct regulation of the <protein>A6H</protein> transduced <protein>AP-1</protein> activation pathway may exist in <cell_type>CD4+ and CD8+ T cell subpopulations</cell_type> .


Cloning and expression of the glucocorticoid receptor from the squirrel monkey ( Saimiri boliviensis boliviensis ) , a glucocorticoid-resistant primate .

Cloning and expression of the <protein>glucocorticoid receptor</protein> from the squirrel monkey ( Saimiri boliviensis boliviensis ) , a glucocorticoid-resistant primate .


New World primates such as the squirrel monkey have elevated cortisol levels and glucocorticoid resistance .


We have shown that the apparent binding affinity of the glucocorticoid receptor in squirrel monkey lymphocytes is 5-fold lower than that in human lymphocytes ( apparent Kd , 20.9 +/- 1.8 and 4.3 +/- 0.2 nmol/L , respectively ; n = 3 ) , consistent with previous studies in mononuclear leukocytes isolated from the two species .

We have shown that the apparent binding affinity of the <protein>glucocorticoid receptor</protein> in <cell_type>squirrel monkey lymphocytes</cell_type> is 5-fold lower than that in <cell_type>human lymphocytes</cell_type> ( apparent Kd , 20.9 +/- 1.8 and 4.3 +/- 0.2 nmol/L , respectively ; n = 3 ) , consistent with previous studies in <cell_type>mononuclear leukocytes</cell_type> isolated from the two species .


As a first step in understanding the mechanism of decreased binding affinity in New World primates , we used reverse transcription-PCR to clone the glucocorticoid receptor from squirrel monkey liver and have compared the sequence to receptor sequences obtained from owl monkey liver , cotton-top tamarin B95-8 cells , and human lymphocytes .

As a first step in understanding the mechanism of decreased binding affinity in New World primates , we used reverse transcription-PCR to clone the <protein>glucocorticoid receptor</protein> from squirrel monkey liver and have compared the sequence to receptor sequences obtained from owl monkey liver , <cell_line>cotton-top tamarin B95-8 cells</cell_line> , and <cell_type>human lymphocytes</cell_type> .


The squirrel monkey glucocorticoid receptor is approximately 97 % identical in nucleotide and amino acid sequence to the human receptor .

The squirrel monkey <protein>glucocorticoid receptor</protein> is approximately 97 % identical in nucleotide and amino acid sequence to the <protein>human receptor</protein> .


The ligand-binding domain ( amino acids 528-777 ) of the squirrel monkey glucocorticoid receptor contains four amino acid differences ( Ser551 to Thr , Ser616 to Ala , Ala618 to Ser , and Ile761 to Leu ) , all of which are present in owl monkey and cotton-top tamarin receptors .

The <protein>ligand-binding domain</protein> ( <protein>amino acids 528-777</protein> ) of the squirrel monkey <protein>glucocorticoid receptor</protein> contains four amino acid differences ( Ser551 to Thr , Ser616 to Ala , Ala618 to Ser , and Ile761 to Leu ) , all of which are present in <protein>owl monkey and cotton-top tamarin receptors</protein> .


The DNA-binding domain ( amino acids 421-486 ) is completely conserved among human , squirrel monkey , owl monkey , and cotton-top tamarin receptors .

The <protein>DNA-binding domain</protein> ( <protein>amino acids 421-486</protein> ) is completely conserved among <protein>human , squirrel monkey , owl monkey , and cotton-top tamarin receptors</protein> .


Twenty-two differences from the human sequence were found in the N-terminal region ( amino acids 1-421 ) of the squirrel monkey receptor .

Twenty-two differences from the human sequence were found in the <protein>N-terminal region</protein> ( <protein>amino acids 1-421</protein> ) of the squirrel monkey receptor .


of the substitutions in the ligand-binding domain matched mutations known to influence binding affinity in other species .

of the substitutions in the <protein>ligand-binding domain</protein> matched mutations known to influence binding affinity in other species .


To determine whether the substitutions per se were responsible for decreased affinity , squirrel monkey and human glucocorticoid receptors were expressed in the TNT Coupled Reticulocyte Lysate System .

To determine whether the substitutions per se were responsible for decreased affinity , squirrel monkey and <protein>human glucocorticoid receptors</protein> were expressed in the TNT Coupled Reticulocyte Lysate System .


Expressions of human and squirrel monkey glucocorticoid receptors and a squirrel monkey receptor in which Phe774 was mutated to Leu ( F774L ) were similar .

Expressions of human and squirrel monkey <protein>glucocorticoid receptors</protein> and a <protein>squirrel monkey receptor</protein> in which Phe774 was mutated to Leu ( F774L ) were similar .


When expressed in the TNT System , squirrel monkey and human glucocorticoid receptors had similar , high affinity binding for dexamethasone ( apparent Kd , 5.9 +/- 1.2 and 4.3 +/- 0.5 nmol/L , respectively ; n = 3 ) , whereas the squirrel monkey F774L receptor had lower affinity binding ( apparent Kd , 20.4 +/- 2.0 nmol/L ; n = 3 ) .

When expressed in the TNT System , squirrel monkey and <protein>human glucocorticoid receptors</protein> had similar , high affinity binding for dexamethasone ( apparent Kd , 5.9 +/- 1.2 and 4.3 +/- 0.5 nmol/L , respectively ; n = 3 ) , whereas the <protein>squirrel monkey F774L receptor</protein> had lower affinity binding ( apparent Kd , 20.4 +/- 2.0 nmol/L ; n = 3 ) .


Thus , substitutions within the ligand-binding domain of the squirrel monkey glucocorticoid receptor can not account for the decreased binding affinity of these receptors in squirrel monkey cells .

Thus , substitutions within the <protein>ligand-binding domain</protein> of the squirrel monkey <protein>glucocorticoid receptor</protein> can not account for the decreased binding affinity of these receptors in <cell_type>squirrel monkey cells</cell_type> .


Rather , the binding affinity is probably influenced by the expression of cytosolic factors that affect glucocorticoid receptor function .

Rather , the binding affinity is probably influenced by the expression of <protein>cytosolic factors</protein> that affect <protein>glucocorticoid receptor</protein> function .


Shared gamma ( c ) subunit within the human interleukin-7 receptor complex .

Shared <protein>gamma ( c ) subunit</protein> within the <protein>human interleukin-7 receptor complex</protein> .


A molecular basis for the pathogenesis of X-linked severe combined immunodeficiency .


Genetic evidence suggests that mutations in the gamma ( c ) receptor subunit cause X-linked severe combined immunodeficiency ( X-SCID ) .

Genetic evidence suggests that mutations in the <protein>gamma ( c ) receptor subunit</protein> cause X-linked severe combined immunodeficiency ( X-SCID ) .


The gamma ( c ) subunit can be employed in receptor complexes for IL-2 , -4 , -7 , -9 , and -15 , and the multiple signaling defects that would result from a defective gamma ( c ) chain in these receptors are proposed to cause the severe phenotype of X-SCID patients .

The <protein>gamma ( c ) subunit</protein> can be employed in <protein>receptor complexes</protein> for <protein>IL-2 , -4 , -7 , -9 , and -15</protein> , and the multiple signaling defects that would result from a defective <protein>gamma ( c ) chain</protein> in these receptors are proposed to cause the severe phenotype of X-SCID patients .


Interestingly , gene disruption of either IL-7 or the IL-7 receptor ( IL-7R ) alpha subunit in mice leads to immunological defects that are similar to human X-SCID .

Interestingly , gene disruption of either <protein>IL-7</protein> or the <protein>IL-7 receptor ( IL-7R ) alpha subunit</protein> in mice leads to immunological defects that are similar to human X-SCID .


These observations suggest the functional importance of gamma ( c ) in the IL-7R complex .

These observations suggest the functional importance of <protein>gamma ( c )</protein> in the <protein>IL-7R complex</protein> .


In the present study , structure/function analyses of the IL-7R complex using a chimeric receptor system demonstrated that gamma ( c ) is indeed critical for IL-7R function .

In the present study , structure/function analyses of the <protein>IL-7R complex</protein> using a <protein>chimeric receptor</protein> system demonstrated that <protein>gamma ( c )</protein> is indeed critical for <protein>IL-7R</protein> function .


Nonetheless , only a limited portion of the cytoplasmic domain of gamma ( c ) is necessary for IL-7R signal transduction .

Nonetheless , only a limited portion of the <protein>cytoplasmic domain</protein> of <protein>gamma ( c )</protein> is necessary for <protein>IL-7R</protein> signal transduction .


Furthermore , replacement of the gamma ( c ) cytoplasmic domain by a severely truncated erythropoeitin receptor does not affect measured IL-7R signaling events .

Furthermore , replacement of the <protein>gamma ( c )</protein> <protein>cytoplasmic domain</protein> by a <protein>severely truncated erythropoeitin receptor</protein> does not affect measured <protein>IL-7R</protein> signaling events .


These findings support a model in which gamma ( c ) serves primarily to activate signal transduction by the IL-7R complex , while IL-7R alpha determines specific signaling events through its association with cytoplasmic signaling molecules .

These findings support a model in which <protein>gamma ( c )</protein> serves primarily to activate signal transduction by the <protein>IL-7R complex</protein> , while <protein>IL-7R alpha</protein> determines specific signaling events through its association with <protein>cytoplasmic signaling molecules</protein> .


Finally , these studies are consistent with the hypothesis that the molecular pathogenesis of X-SCID is due primarily to gamma ( c ) -mediated defects in the IL-7 /IL-7R system

Finally , these studies are consistent with the hypothesis that the molecular pathogenesis of X-SCID is due primarily to <protein>gamma ( c )</protein> -mediated defects in the <protein>IL-7</protein> <protein>/IL-7R</protein> system


S-allyl cysteine inhibits activation of nuclear factor kappa B in human T cells .

S-allyl cysteine inhibits activation of <protein>nuclear factor kappa B</protein> in <cell_type>human T cells</cell_type> .


Reactive oxygen species are involved in signal transduction pathways leading to nuclear factor kappa B ( NF-kappa B ) activation which has been implicated in the regulation of gene transcription .

Reactive oxygen species are involved in signal transduction pathways leading to <protein>nuclear factor kappa B</protein> ( <protein>NF-kappa B</protein> ) activation which has been implicated in the regulation of gene transcription .


We recently reported that a garlic compound , S-allyl cysteine ( SAC ) , protects bovine pulmonary artery endothelial cells from oxidant injury induced by hydrogen peroxide ( H2O2 ) .

We recently reported that a garlic compound , S-allyl cysteine ( SAC ) , protects <cell_type>bovine pulmonary artery endothelial cells</cell_type> from oxidant injury induced by hydrogen peroxide ( H2O2 ) .


In this study we determined the effects of SAC on NF-kappa B activation in human T lymphocytes ( Jurkat cells ) induced by tumor necrosis factor alpha ( TNF- alpha ) and H2O2 .

In this study we determined the effects of SAC on <protein>NF-kappa B</protein> activation in <cell_type>human T lymphocytes</cell_type> ( <cell_line>Jurkat cells</cell_line> ) induced by <protein>tumor necrosis factor alpha</protein> ( <protein>TNF- alpha</protein> ) and H2O2 .


Activated NF-kappa B in nuclear extracts was measured by an electrophoretic mobility shift assay using 32P-labeled probe .

Activated <protein>NF-kappa B</protein> in nuclear extracts was measured by an electrophoretic mobility shift assay using <dna>32P-labeled probe</dna> .


SAC consistently exhibited a dose-dependent inhibition of NF-kappa B activation induced by both TNF-alpha and H2O2 .

SAC consistently exhibited a dose-dependent inhibition of <protein>NF-kappa B</protein> activation induced by both <protein>TNF-alpha</protein> and H2O2 .


Supershift with specific antibodies to NF-kappa B subunits confirmed that the inducible retarded bands observed in the EMSA and p65-p50 heterodimer of the NF-kappa B/Rel protein .

Supershift with specific antibodies to <protein>NF-kappa B subunits</protein> confirmed that the inducible retarded bands observed in the EMSA and <protein>p65-p50 heterodimer</protein> of the <protein>NF-kappa B/Rel protein</protein> .


Our data suggest that SAC may act via antioxidant mechanisms to block NF-kappa B activation in Jurkat cells .

Our data suggest that SAC may act via antioxidant mechanisms to block <protein>NF-kappa B</protein> activation in <cell_line>Jurkat cells</cell_line> .


Elf-2 , a rhombotin-2 binding ets transcription factor : discovery and potential role in T cell leukemia .

<protein>Elf-2</protein> , a <protein>rhombotin-2 binding ets transcription factor</protein> : discovery and potential role in T cell leukemia .


Rhombotin-2 ( RBTN-2 ) is a proto-oncogene only in the context of T lymphocytes .

<dna>Rhombotin-2</dna> ( <dna>RBTN-2</dna> ) is a <dna>proto-oncogene</dna> only in the context of <cell_type>T lymphocytes</cell_type> .


We postulated that the oncogenic effect of RBTN-2 in T cells is likely mediated by binding protein ( s ) with T cell-specific expression .

We postulated that the oncogenic effect of <protein>RBTN-2</protein> in T cells is likely mediated by <protein>binding protein</protein> ( s ) with T cell-specific expression .


By screening a T cell cDNA library , we identified a novel ets transcription factor that binds RBTN-2 .

By screening a T cell <dna>cDNA library</dna> , we identified a <protein>novel ets transcription factor</protein> that binds <protein>RBTN-2</protein> .


This protein was named elf-2 because its DNA-binding domain is virtually identical to that of ets family member elf-1 .

This protein was named <protein>elf-2</protein> because its <protein>DNA-binding domain</protein> is virtually identical to that of <protein>ets family member</protein> <protein>elf-1</protein> .


Northern analyses showed similar levels of two elf-2 transcripts ( 3.5 kb and 3.8 kb ) in all tissues except thymus .

Northern analyses showed similar levels of two <rna>elf-2 transcripts</rna> ( 3.5 kb and 3.8 kb ) in all tissues except thymus .


Thymocytes expressed four- to 10-fold greater amounts of the 3.5 kb transcript than other tissues .

<cell_type>Thymocytes</cell_type> expressed four- to 10-fold greater amounts of the <rna>3.5 kb transcript</rna> than other tissues .


Sequence analyses of cDNA clones indicated that these transcripts encode proteins differing only at their amino termini , and likely represent alternatively spliced isoforms .

Sequence analyses of <dna>cDNA clones</dna> indicated that these transcripts encode proteins differing only at their <protein>amino termini</protein> , and likely represent alternatively spliced isoforms .


These isoforms ( elf-2a and elf-2b ) contain identical RBTN-2 binding regions and DNA-binding domains .

These isoforms ( <protein>elf-2a</protein> and <protein>elf-2b</protein> ) contain identical <protein>RBTN-2 binding regions</protein> and <protein>DNA-binding domains</protein> .


Elf-2b lacks a putative transactivation domain .

<protein>Elf-2b</protein> lacks a <protein>putative transactivation domain</protein> .


The expression patterns suggest that RBTN-2 normally interacts equally with elf-2a and elf-2b .

The expression patterns suggest that <protein>RBTN-2</protein> normally interacts equally with <protein>elf-2a</protein> and <protein>elf-2b</protein> .


In contrast , when RBTN-2 is inappropriately expressed in T cells , RBTN-2 would interact predominantly with elf-2b ; this interaction may lead to T cell proliferation .

In contrast , when <protein>RBTN-2</protein> is inappropriately expressed in <cell_type>T cells</cell_type> , <protein>RBTN-2</protein> would interact predominantly with <protein>elf-2b</protein> ; this interaction may lead to T cell proliferation .


Transcription factor effects on chromosome constitution of cell hybrids .

<protein>Transcription factor</protein> effects on chromosome constitution of <cell_line>cell hybrids</cell_line> .


When immunoglobulin ( Ig ) -secreting plasmacytomas are fused to a T-cell lymphoma , Ig gene expression ceases in greater than 95 % of the resulting hybrids .

When <cell_line>immunoglobulin ( Ig ) -secreting plasmacytomas</cell_line> are fused to a <cell_type>T-cell lymphoma</cell_type> , <dna>Ig gene</dna> expression ceases in greater than 95 % of the resulting hybrids .


In the rare hybrids that continue to express Ig , all other tested B lymphocyte-specific genes also remain active .

In the rare hybrids that continue to express Ig , all other tested <dna>B lymphocyte-specific genes</dna> also remain active .


The low frequency with which these Ig-expressing hybrids are recovered , along with the fact that cell fusions can lead to chromosome loss , led us to propose that this rare phenotype was due to loss of a T-cell-derived chromosome encoding a factor or factors with gene silencing activity .

The low frequency with which these <cell_line>Ig-expressing hybrids</cell_line> are recovered , along with the fact that cell fusions can lead to chromosome loss , led us to propose that this rare phenotype was due to loss of a <protein>T-cell-derived chromosome encoding a factor</protein> or factors with gene silencing activity .


To identify the relevant chromosome , we have used a polymerase chain reaction ( PCR ) -assisted method of chromosome mapping to analyze both Ig-silenced ( common ) and Ig-expressing ( rare ) hybrids .

To identify the relevant chromosome , we have used a polymerase chain reaction ( PCR ) -assisted method of chromosome mapping to analyze both <cell_line>Ig-silenced ( common ) and Ig-expressing ( rare ) hybrids</cell_line> .


Although no single chromosome was found to correlate with Ig gene silencing , we discovered that the two types of hybrids had undergone distinct patterns of chromosome loss .

Although no single chromosome was found to correlate with <dna>Ig gene</dna> silencing , we discovered that the two types of hybrids had undergone distinct patterns of chromosome loss .


Moreover , we found that ectopic expression of a B-cell-specific transcription factor ( Oct-2 ) dramatically altered both the phenotype and chromosome constitution of hybrids arising in these cell fusions .

Moreover , we found that ectopic expression of a <protein>B-cell-specific transcription factor</protein> ( <protein>Oct-2</protein> ) dramatically altered both the phenotype and chromosome constitution of hybrids arising in these cell fusions .


Reactivation of Kaposi 's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator , a homolog of the EBV R protein .

Reactivation of Kaposi 's sarcoma-associated herpesvirus infection from latency by expression of the <protein>ORF 50 transactivator</protein> , a homolog of the <protein>EBV R protein</protein> .


Kaposi 's sarcoma ( KS ) -associated herpesvirus ( KSHV ) , or human herpesvirus 8 , is a lymphotropic virus strongly linked to several AIDS-related neoplasms .


The primary reservoir of infection consists of latently infected B lymphocytes and possibly other mononuclear cells .

The primary reservoir of infection consists of latently infected <cell_type>B lymphocytes</cell_type> and possibly other <cell_type>mononuclear cells</cell_type> .


Viral reactivation from latency and spread from this lymphoid reservoir is presumably required for development of nonlymphoid tumors like KS .


Here we show that deregulated expression of a single viral gene , ORF 50 , which encodes a transactivator able to selectively upregulate delayed-early viral genes , suffices to disrupt latency and induce the lytic gene cascade in latently infected B cells .

Here we show that deregulated expression of a single <dna>viral gene</dna> , <dna>ORF 50</dna> , which encodes a transactivator able to selectively upregulate <dna>delayed-early viral genes</dna> , suffices to disrupt latency and induce the lytic gene cascade in <cell_type>latently infected B cells</cell_type> .


The identification of this gene opens the way to studies of the physiologic mechanisms controlling reactvation of KSHV from latency .


Copyright 1998 Academic Press .


Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation : requirement for CD28 up-regulation of RE/AP .

<protein>Nuclear factor of activated T cells</protein> and <protein>AP-1</protein> are insufficient for <dna>IL-2 promoter</dna> activation : requirement for <protein>CD28</protein> up-regulation of <protein>RE/AP</protein> .


IL-2 gene transcription in T cells requires both TCR and costimulatory signals .

<protein>IL-2</protein> gene transcription in <cell_type>T cells</cell_type> requires both TCR and costimulatory signals .


IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation .

<dna>IL-2 promoter</dna> activation in <cell_line>Jurkat T cells</cell_line> stimulated with superantigen presented by <cell_line>Raji B cells</cell_line> requires <protein>CD28</protein> activation .


The addition of rCTLA4Ig , which blocks CD28 binding to its ligand , to the cultures decreased IL-2 promoter activation by > 80 % .

The addition of rCTLA4Ig , which blocks <protein>CD28</protein> binding to its ligand , to the cultures decreased <dna>IL-2 promoter</dna> activation by > 80 % .


Interestingly , CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells ( NFAT ) or AP-1 reporters .

Interestingly , CTLA4Ig did not significantly inhibit the activation of either <protein>NF of activated T cells</protein> ( <protein>NFAT</protein> ) or <dna>AP-1 reporters</dna> .


Therefore , activation of NFAT and AP-1 is insufficient for IL-2 promoter activation .

Therefore , activation of <protein>NFAT</protein> and <protein>AP-1</protein> is insufficient for <dna>IL-2 promoter</dna> activation .


In contrast , an RE/AP reporter was blocked by CTLA4Ig by > 90 % .

In contrast , an <protein>RE/AP</protein> reporter was blocked by CTLA4Ig by > 90 % .


Thus , the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites .

Thus , the requirement for <protein>CD28</protein> in <dna>IL-2 promoter</dna> activation appears to be due to <protein>RE/AP</protein> and not the <dna>NFAT or AP-1 sites</dna> .


In addition , these data suggest that transcriptional activation of RE/AP is not mediated by NFAT , because activation of a NFAT reporter is not affected by the addition of CTLA4Ig .

In addition , these data suggest that transcriptional activation of <protein>RE/AP</protein> is not mediated by <protein>NFAT</protein> , because activation of a <protein>NFAT</protein> reporter is not affected by the addition of CTLA4Ig .


The control of lytic replication of Epstein-Barr virus in B lymphocytes ( Review ) .

The control of lytic replication of Epstein-Barr virus in <cell_type>B lymphocytes</cell_type> ( Review ) .


Uncontrolled replication of a virus , which is harmful to the host is also disadvantageous to the virus .


Most viruses can not compete with the various immune mechanisms and become eliminated in the course of infection .


Therefore , only the time between infection and eradication remains for these viruses to proliferate .


A few viruses , like the Herpesviruses or the papillomaviruses , however , have developed a sophisticated strategy for persisting lifelong , usually asymptomatically in the host , hiding from the immune system and producing infectious progeny at the same time .


This strategy depends on a separation of latency and the lytic replication , either by time due to differentiation-dependent mechanisms or by spatial separation as the result of different host cell types .


Both are true for the Epstein-Barr virus ( EBV ) .


B cells and epithelial cells have a pivotal role in the life cycle of the virus .

<cell_type>B cells</cell_type> and <cell_type>epithelial cells</cell_type> have a pivotal role in the life cycle of the virus .


The former can become latently infected and are thought to be the virus reservoir in vivo , whereas the latter were shown to be permissive for lytic replication .


However , replication of EBV in vivo is controlled primarily by host immune mechanisms selecting for cells that are not permissive for viral replication as the result of a particular set of transcription factors .

However , replication of EBV in vivo is controlled primarily by host immune mechanisms selecting for cells that are not permissive for viral replication as the result of a particular set of <protein>transcription factors</protein> .


These factors control the activity of the regulatory immediate-early genes and , in addition , lytic and latent cycle regulatory genes negatively interfere with each other and thus link cellular and viral gene regulatory mechanisms .

These factors control the activity of the <dna>regulatory immediate-early genes</dna> and , in addition , lytic and latent cycle regulatory genes negatively interfere with each other and thus link cellular and <dna>viral gene</dna> regulatory mechanisms .


Disturbance of both the immune surveillance as well as viral gene regulation may result in EBV-associated disease .

Disturbance of both the immune surveillance as well as <dna>viral gene</dna> regulation may result in EBV-associated disease .


Adaptor function for the Syk kinases-interacting protein 3BP2 in IL-2 gene activation .

Adaptor function for the <protein>Syk kinases-interacting protein</protein> <protein>3BP2</protein> in <protein>IL-2</protein> gene activation .


Syk-family tyrosine kinases are essential for lymphocyte development and activation .

<protein>Syk-family tyrosine kinases</protein> are essential for lymphocyte development and activation .


Using a yeast two-hybrid screen to identify Syk kinases-interacting proteins ( SKIPs ) , we isolated 3BP2 , an Abl SH3-interacting protein of unknown function .

Using a yeast two-hybrid screen to identify <protein>Syk kinases-interacting proteins</protein> ( <protein>SKIPs</protein> ) , we isolated <protein>3BP2</protein> , an <protein>Abl SH3-interacting protein</protein> of unknown function .


3BP2 was selectively expressed in hematopoietic/lymphoid tissues and bound via its SH2 domain activated Syk-family kinases in mammalian cells , including in antigen receptor-stimulated T cells .

<protein>3BP2</protein> was selectively expressed in hematopoietic/lymphoid tissues and bound via its <protein>SH2 domain activated Syk-family kinases</protein> in <cell_type>mammalian cells</cell_type> , including in <cell_type>antigen receptor-stimulated T cells</cell_type> .


In addition to Zap-70 , the 3BP2 SH2 domain associated in vitro with LAT , Grb2 , PLCgamma1 , and Cbl from activated T cell lysates .

In addition to <protein>Zap-70</protein> , the <protein>3BP2 SH2 domain</protein> associated in vitro with <protein>LAT</protein> , <protein>Grb2</protein> , <protein>PLCgamma1</protein> , and <protein>Cbl</protein> from activated T cell lysates .


Transient 3BP2 overexpression induced transcriptional activation of the IL-2 promoter and its NFAT or AP-1 elements .

Transient <protein>3BP2</protein> overexpression induced transcriptional activation of the <dna>IL-2 promoter</dna> and its <dna>NFAT or AP-1 elements</dna> .


This activity was dependent on the SH2 and pleckstrin-homology domains of 3BP2 , and required functional Syk kinases , Ras , and calcineurin .

This activity was dependent on the <protein>SH2</protein> and <protein>pleckstrin-homology domains</protein> of <protein>3BP2</protein> , and required functional <protein>Syk kinases</protein> , <protein>Ras</protein> , and <protein>calcineurin</protein> .


Thus , 3BP2 is an important adaptor that may couple activated Zap-70/Syk to a LAT-containing signaling complex involved in TCR-mediated gene transcription .

Thus , <protein>3BP2</protein> is an important adaptor that may couple activated <protein>Zap-70/Syk</protein> to a <protein>LAT-containing signaling complex</protein> involved in TCR-mediated gene transcription .


In vitro suppression of programmed cell death of B cells by tissue inhibitor of metalloproteinases-1 .

In vitro suppression of programmed cell death of <cell_type>B cells</cell_type> by tissue inhibitor of <protein>metalloproteinases-1</protein> .


Cellular pathways for induction of programmed cell death ( PCD ) have been identified , but little is known about specific extracellular matrix processes that may affect apoptosis along those pathways .


In this study , a series of Burkitt 's lymphoma ( BL ) cell lines were assayed for their expression of tissue inhibitor of metalloproteinases ( TIMP ) -1 .

In this study , a series of <cell_line>Burkitt 's lymphoma ( BL ) cell lines</cell_line> were assayed for their expression of <protein>tissue inhibitor of metalloproteinases ( TIMP ) -1</protein> .


Results indicate that TIMP-1-positive BL lines show resistance to cold-shock-induced apoptosis .

Results indicate that <cell_line>TIMP-1-positive BL lines</cell_line> show resistance to cold-shock-induced apoptosis .


Furthermore , recombinant TIMP-1 , but not TIMP-2 or a synthetic metalloproteinase inhibitor ( BB-94 ) , confers resistance to apoptosis induced by both CD95-dependent and -independent ( cold shock , serum deprivation , and gamma-radiation ) pathways in TIMP-1-negative BL lines .

Furthermore , recombinant <protein>TIMP-1</protein> , but not <protein>TIMP-2</protein> or a synthetic metalloproteinase inhibitor ( BB-94 ) , confers resistance to apoptosis induced by both CD95-dependent and -independent ( cold shock , serum deprivation , and gamma-radiation ) pathways in <cell_line>TIMP-1-negative BL lines</cell_line> .


TIMP-1 suppression of PCD is not due to metalloproteinase inhibition , as reduction and alkylation of the TIMP-1 did not abolish this activity .

<protein>TIMP-1</protein> suppression of PCD is not due to <protein>metalloproteinase</protein> inhibition , as reduction and alkylation of the <protein>TIMP-1</protein> did not abolish this activity .


Retroviral induction of TIMP-1 not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum , while controls underwent apoptosis .

Retroviral induction of <protein>TIMP-1</protein> not only resulted in cell survival but also in continued DNA synthesis for up to 5 d in the absence of serum , while controls underwent apoptosis .


This resistance to apoptosis is reversed by anti-TIMP-1 antibodies , demonstrating that secreted TIMP-1 is active in blocking apoptosis .

This resistance to apoptosis is reversed by <protein>anti-TIMP-1 antibodies</protein> , demonstrating that secreted <protein>TIMP-1</protein> is active in blocking apoptosis .


Furthermore , TIMP-1 upregulation induced expression of Bcl-XL but not Bcl-2 as well as decreased NF-kappaB activity as compared with controls .

Furthermore , <protein>TIMP-1</protein> upregulation induced expression of <protein>Bcl-XL</protein> but not <protein>Bcl-2</protein> as well as decreased <protein>NF-kappaB</protein> activity as compared with controls .


These results demonstrate that TIMP-1 suppresses apoptosis in B cells and suggests a novel activity for TIMP-1 in tissue homeostasis .

These results demonstrate that <protein>TIMP-1</protein> suppresses apoptosis in <cell_type>B cells</cell_type> and suggests a novel activity for <protein>TIMP-1</protein> in tissue homeostasis .


Spi-1/PU.1 proto-oncogene induces opposite effects on monocytic and erythroid differentiation of K562 cells .

<dna>Spi-1/PU.1</dna> <dna>proto-oncogene</dna> induces opposite effects on monocytic and erythroid differentiation of <cell_line>K562 cells</cell_line> .


Spi-1/PU.1 is a hematopoietic transcription factor of the Ets family .

<protein>Spi-1/PU.1</protein> is a <protein>hematopoietic transcription factor</protein> of the <protein>Ets family</protein> .


To analyze the effects of ectopic expression of spi-1 on the proliferation/differentiation of human myeloid leukemia cells , K562 cells were stably transfected with a spi-1 expression vector .

To analyze the effects of ectopic expression of <protein>spi-1</protein> on the proliferation/differentiation of <cell_type>human myeloid leukemia cells</cell_type> , <cell_line>K562 cells</cell_line> were stably transfected with a <dna>spi-1 expression vector</dna> .


The transfected cell lines expressed elevated levels of spi-1 mRNA and protein and high Spi-1 -DNA binding activity .

The <cell_line>transfected cell lines</cell_line> expressed elevated levels of <rna>spi-1 mRNA</rna> and protein and high <protein>Spi-1</protein> -DNA binding activity .


The spi-1 transfected cells showed reduced growth rates and reduced clonogenic cell growth .

The <cell_line>spi-1 transfected cells</cell_line> showed reduced growth rates and reduced clonogenic cell growth .


When the erythroid and monocytic differentiation markers were analyzed , spi-1 overexpression resulted in opposite effects : erythroid differentiation was significantly inhibited in spi-1 transfectants , while spi-1 overexpression increased the monocytic differentiation of cells .

When the erythroid and monocytic differentiation markers were analyzed , <protein>spi-1</protein> overexpression resulted in opposite effects : erythroid differentiation was significantly inhibited in <cell_line>spi-1 transfectants</cell_line> , while <protein>spi-1</protein> overexpression increased the monocytic differentiation of cells .


These results indicate a differential role of Spi-1 on the differentiation of human myeloid leukemia cells .

These results indicate a differential role of <dna>Spi-1</dna> on the differentiation of <cell_line>human myeloid leukemia cells</cell_line> .


Copyright 1998 Academic Press .


In vivo function of an interleukin 2 receptor beta chain ( IL-2Rbeta ) /IL-4Ralpha cytokine receptor chimera potentiates allergic airway disease .

In vivo function of an <protein>interleukin 2 receptor beta chain</protein> <protein>( IL-2Rbeta ) /IL-4Ralpha cytokine receptor chimera</protein> potentiates allergic airway disease .


Strength of T cell receptor ( TCR ) signaling , coreceptors , costimulation , antigen-presenting cell type , and cytokines all play crucial roles in determining the efficiency with which type 2 T lymphocytes ( Th2 , Tc2 ) develop from uncommitted precursors .

Strength of <protein>T cell receptor</protein> ( <protein>TCR</protein> ) signaling , <protein>coreceptors</protein> , costimulation , <cell_type>antigen-presenting cell type</cell_type> , and cytokines all play crucial roles in determining the efficiency with which <cell_type>type 2 T lymphocytes</cell_type> ( <cell_type>Th2</cell_type> , <cell_type>Tc2</cell_type> ) develop from <protein>uncommitted precursors</protein> .