Promoter analysis revealed that a GATA site in a cryptic promoter in the second intron was essential and sufficient for the TAL1- and LMO-dependent transcriptional activation , and GATA3 binds to this site .

Promoter analysis revealed that a <dna>GATA site</dna> in a <dna>cryptic promoter</dna> in the <dna>second intron</dna> was essential and sufficient for the TAL1- and LMO-dependent transcriptional activation , and <protein>GATA3</protein> binds to this site .


In addition , forced expression of GATA3 potentiated the induction of RALDH2 by TAL1 and LMO , and these three factors formed a complex in vivo .

In addition , forced expression of <protein>GATA3</protein> potentiated the induction of <protein>RALDH2</protein> by <protein>TAL1</protein> and <protein>LMO</protein> , and these three factors formed a complex in vivo .


Furthermore , a TAL1 mutant not binding to DNA also activated the transcription of RALDH2 in the presence of LMO and GATA3 .

Furthermore , a <protein>TAL1</protein> mutant not binding to DNA also activated the transcription of <protein>RALDH2</protein> in the presence of <protein>LMO</protein> and <protein>GATA3</protein> .


Collectively , we have identified the RALDH2 gene as a first example of direct transcriptional target genes regulated by TAL1 and LMO in T-ALL .

Collectively , we have identified the <dna>RALDH2 gene</dna> as a first example of direct <dna>transcriptional target genes</dna> regulated by <protein>TAL1</protein> and <protein>LMO</protein> in T-ALL .


In this case , TAL1 and LMO act as cofactors for GATA3 to activate the transcription of RALDH2

In this case , <protein>TAL1</protein> and <protein>LMO</protein> act as cofactors for <protein>GATA3</protein> to activate the transcription of <protein>RALDH2</protein>


Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to age and to sport activity .

<protein>Glucocorticoid receptors</protein> in <cell_type>human peripheral blood mononuclear cells</cell_type> in relation to age and to sport activity .


Glucocorticoid receptors ( GR ) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues .

<protein>Glucocorticoid receptors</protein> ( <protein>GR</protein> ) are ubiquitous molecules and are present also in the hippocampus and in several other nervous and immune tissues .


Peripheral blood mononuclear cells ( PBMCs ) are a good model for studies of GR in humans .

<cell_type>Peripheral blood mononuclear cells</cell_type> ( <cell_type>PBMCs</cell_type> ) are a good model for studies of <protein>GR</protein> in humans .


Glucocorticoids are important for maintaining cellular and humoral homeostasis and are key mediators of neuroendocrine-immune regulatory interactions .


The increase of cortisol is immunosuppressive and reduces GR concentration both in nervous and immune systems .

The increase of cortisol is immunosuppressive and reduces <protein>GR</protein> concentration both in nervous and immune systems .


Variation of glucocorticoids in healthy aged subjects and athletes has been shown .


Prompted by these results , we have investigated in man a possible relationship between GR binding capacity in the PBMCs and age , in relation also to plasma testosterone and cortisol .

Prompted by these results , we have investigated in man a possible relationship between <protein>GR</protein> binding capacity in the <cell_type>PBMCs</cell_type> and age , in relation also to plasma testosterone and cortisol .


The same parameters have been examined in a group of soccer players for comparison with the sedentary group .


GR binding capacity was higher in younger subjects than in older ones , and lower in the group of athletes than in the younger and older sedentary subjects .

<protein>GR</protein> binding capacity was higher in younger subjects than in older ones , and lower in the group of athletes than in the younger and older sedentary subjects .


In the sedentary group a negative correlation was present between GR binding capacity and age .

In the sedentary group a negative correlation was present between <protein>GR</protein> binding capacity and age .


Plasma cortisol was higher and testosterone lower in the athletes ; they were negatively correlated in athletes and positively correlated in the sedentary subjects .


The results for athletes agree with their lower anabolic/catabolic balance .


The mechanism of reduced GR levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis .

The mechanism of reduced <protein>GR</protein> levels in relation to age and sport activity could involve a loss or an involution of receptor synthesis .


However other possibilities , such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different cytokine production , can not be excluded .

However other possibilities , such as altered distribution of lymphocyte subpopulations with different receptor concentrations and with different <protein>cytokine</protein> production , can not be excluded .


Several neuroendocrine-immune interactions could be responsible for reduced GR levels with age and sport activity in man .

Several neuroendocrine-immune interactions could be responsible for reduced <protein>GR</protein> levels with age and sport activity in man .


Glycation-dependent , reactive oxygen species-mediated suppression of the insulin gene promoter activity in HIT cells .

Glycation-dependent , reactive oxygen species-mediated suppression of the insulin gene promoter activity in <cell_type>HIT cells</cell_type> .


Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from pancreatic beta cells , accompanied by a decrease in the insulin content of the cells .

Prolonged poor glycemic control in non-insulin-dependent diabetes mellitus patients often leads to a decline in insulin secretion from <cell_type>pancreatic beta cells</cell_type> , accompanied by a decrease in the insulin content of the cells .


As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to pancreatic beta cells , we induced glycation in HIT-T15 cells using a sugar with strong deoxidizing activity , D-ribose , and examined the effects on insulin gene transcription .

As a step toward elucidating the pathophysiological background of the so-called glucose toxicity to <cell_type>pancreatic beta cells</cell_type> , we induced glycation in <cell_type>HIT-T15 cells</cell_type> using a sugar with strong deoxidizing activity , D-ribose , and examined the effects on insulin gene transcription .


The results of reporter gene analyses revealed that the insulin gene promoter is more sensitive to glycation than the control beta-actin gene promoter ; approximately 50 and 80 % of the insulin gene promoter activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose , respectively .

The results of <dna>reporter gene</dna> analyses revealed that the <dna>insulin gene promoter</dna> is more sensitive to glycation than the control <dna>beta-actin gene promoter</dna> ; approximately 50 and 80 % of the <dna>insulin gene promoter</dna> activity was lost when the cells were kept for 3 d in the presence of 40 and 60 mM D-ribose , respectively .


In agreement with this , decrease in the insulin mRNA and insulin content was observed in the glycation-induced cells .

In agreement with this , decrease in the <rna>insulin mRNA</rna> and insulin content was observed in the <cell_type>glycation-induced cells</cell_type> .


Also , gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an insulin gene transcription factor , PDX-1/IPF1/STF-1 .

Also , gel mobility shift analyses using specific antiserum revealed decrease in the DNA-binding activity of an <protein>insulin gene transcription factor</protein> , <protein>PDX-1/IPF1/STF-1</protein> .


These effects of D-ribose seemed almost irreversible but could be prevented by addition of 1 mM aminoguanidine or 10 mM N-acetylcysteine , thus suggesting that glycation and reactive oxygen species , generated through the glycation reaction , serve as mediators of the phenomena .


These observations suggest that protein glycation in pancreatic beta cells , which occurs in vivo under chronic hyperglycemia , suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity .

These observations suggest that protein glycation in <cell_type>pancreatic beta cells</cell_type> , which occurs in vivo under chronic hyperglycemia , suppresses insulin gene transcription and thus can explain part of the beta cell glucose toxicity .


Nuclear factor-kappa B activity in T cells from patients with rheumatic diseases : a preliminary report .

<protein>Nuclear factor-kappa B</protein> activity in <cell_type>T cells</cell_type> from patients with rheumatic diseases : a preliminary report .


OBJECTIVE : The NF-kappa B/Rel family of transcription factors regulates the expression of many genes involved in the immune or inflammatory response at the transcriptional level .

OBJECTIVE : The <protein>NF-kappa B/Rel family</protein> of <protein>transcription factors</protein> regulates the expression of many genes involved in the immune or inflammatory response at the transcriptional level .


The aim of this study was to determine whether distinctive patterns of NF-kappa B activation are seen in different forms of joint disease .

The aim of this study was to determine whether distinctive patterns of <protein>NF-kappa B</protein> activation are seen in different forms of joint disease .


METHODS : The DNA binding activity of these nucleoproteins was examined in purified synovial and peripheral T cells from patients with various chronic rheumatic diseases ( 12 : four with rheumatoid arthritis ; five with spondyloarthropathies ; and three with osteoarthritis ) .

METHODS : The DNA binding activity of these <protein>nucleoproteins</protein> was examined in purified <cell_type>synovial and peripheral T cells</cell_type> from patients with various chronic rheumatic diseases ( 12 : four with rheumatoid arthritis ; five with spondyloarthropathies ; and three with osteoarthritis ) .


RESULTS : Electrophoretic mobility shift assays disclosed two specific complexes bound to a NF-kappa B specific 32P-labelled oligonucleotide in nucleoproteins extracted from purified T cells isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis .

RESULTS : Electrophoretic mobility shift assays disclosed two specific complexes bound to a <protein>NF-kappa B</protein> specific 32P-labelled oligonucleotide in <protein>nucleoproteins</protein> extracted from <cell_type>purified T cells</cell_type> isolated from synovial fluid and peripheral blood of patients with rheumatoid arthritis .


The complexes consisted of p50/p50 homodimers and p50/p65 heterodimers .

The <protein>complexes</protein> consisted of <protein>p50/p50 homodimers</protein> and p50/p65 heterodimers .


Increased NF-kappa B binding to DNA in synovial T cells was observed relative to peripheral T cells .

Increased <protein>NF-kappa B</protein> binding to DNA in <cell_type>synovial T cells</cell_type> was observed relative to peripheral T cells .


In non-rheumatoid arthritis , binding of NF-kappa B in synovial T cells was exclusively mediated by p50/p50 homodimers .

In non-rheumatoid arthritis , binding of <protein>NF-kappa B</protein> in <cell_type>synovial T cells</cell_type> was exclusively mediated by <protein>p50/p50 homodimers</protein> .


CONCLUSION : Overall , the results suggest that NF-kappa B may play a central part in the activation of infiltrating T cells in chronic rheumatoid arthritis .

CONCLUSION : Overall , the results suggest that <protein>NF-kappa B</protein> may play a central part in the activation of <cell_type>infiltrating T cells</cell_type> in chronic rheumatoid arthritis .


The activation of this nuclear factor is qualitatively different in rheumatoid synovial T cells to that in other forms of non-rheumatoid arthritis ( for example , osteoarthritis , spondyloarthropathies ) .

The activation of this nuclear factor is qualitatively different in <cell_type>rheumatoid synovial T cells</cell_type> to that in other forms of non-rheumatoid arthritis ( for example , osteoarthritis , spondyloarthropathies ) .


X chromosome inactivation patterns in normal females .

<dna>X chromosome</dna> inactivation patterns in normal females .


Since one of the two X chromosomes is randomly inactivated at an early stage of female embryonic development , X-linked markers have been used to study the origin and development of various neoplastic disorders in affected heterozygous women ; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia .

Since one of the two <dna>X chromosomes</dna> is randomly inactivated at an early stage of female embryonic development , <protein>X-linked markers</protein> have been used to study the origin and development of various neoplastic disorders in affected heterozygous women ; clonality assays have provided a useful tool to the understanding of the mechanisms underlying the development of neoplasia .


Recently , a technique of clonal analysis has been devised that takes advantage of a highly polymorphic short tandem repeat within the X-linked human androgen receptor ( AR ) gene , resulting in a heterozygosity rate approaching 90 % .

Recently , a technique of clonal analysis has been devised that takes advantage of a highly polymorphic <dna>short tandem repeat</dna> within the <dna>X-linked human androgen receptor ( AR ) gene</dna> , resulting in a heterozygosity rate approaching 90 % .


The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies , one of the more troublesome being the possibility of a modification of the pattern of X- chromosome inactivation pattern in blood cells of elderly women .

The rapid expansion of the number of women now suitable for X inactivation analysis has however given rise to new controversies , one of the more troublesome being the possibility of a modification of the pattern of <dna>X- chromosome</dna> inactivation pattern in <cell_type>blood cells</cell_type> of elderly women .


In the present study we analyze with the AR assay a group of 166 healthy females aged between 8 and 94 years , with no history of genetic or neoplastic familial disorders .


We failed to find any correlation between age and X- chromosome inactivation pattern ( r = 0.17 ) , even subdividing the subjects in different age groups according to the criteria used by other researchers , and therefore reaffirm that , when tested for with well-standardized and accurate criteria , extremely unbalanced inactivation of the X chromosome is a truly uncommon phenomenon in normal women .

We failed to find any correlation between age and <dna>X- chromosome</dna> inactivation pattern ( r = 0.17 ) , even subdividing the subjects in different age groups according to the criteria used by other researchers , and therefore reaffirm that , when tested for with well-standardized and accurate criteria , extremely unbalanced inactivation of the <dna>X chromosome</dna> is a truly uncommon phenomenon in normal women .


Copyright 1998 Academic Press .


The role of Stat4 in species-specific regulation of Th cell development by type I IFNs .

The role of <protein>Stat4</protein> in species-specific regulation of Th cell development by <protein>type I IFNs</protein> .


Type I IFNs ( IFN-alpha/beta ) , in addition to IL-12 , have been shown to play an important role in the differentiation of human , but not mouse , Th cells .

<protein>Type I IFNs</protein> ( <protein>IFN-alpha/beta</protein> ) , in addition to <protein>IL-12</protein> , have been shown to play an important role in the differentiation of human , but not mouse , <cell_type>Th cells</cell_type> .


We show here that IFN-alpha/beta act directly on human T cells to drive Th1 development , bypassing the need for IL-12 -induced signaling , whereas IFN-alpha can not substitute IL-12 for mouse Th1 development .

We show here that <protein>IFN-alpha/beta</protein> act directly on <cell_type>human T cells</cell_type> to drive Th1 development , bypassing the need for <protein>IL-12</protein> -induced signaling , whereas <protein>IFN-alpha</protein> can not substitute <protein>IL-12</protein> for mouse Th1 development .


The molecular basis for this species specificity is that IFN-alpha/beta activate Stat4 in differentiating human , but not mouse , Th cells .

The molecular basis for this species specificity is that <protein>IFN-alpha/beta</protein> activate <protein>Stat4</protein> in differentiating human , but not mouse , <cell_type>Th cells</cell_type> .


Unlike IL-12 , which acts only on Th1 cells , IFN-alpha/beta can activate Stat4 not only in human Th1 , but also in Th2 cells .

Unlike <protein>IL-12</protein> , which acts only on <cell_type>Th1 cells</cell_type> , <protein>IFN-alpha/beta</protein> can activate <protein>Stat4</protein> not only in <cell_type>human Th1</cell_type> , but also in <cell_type>Th2 cells</cell_type> .


However , restimulation of human Th2 lines and clones in the presence of IFN-alpha does not induce the production of IFN-gamma .

However , restimulation of <cell_line>human Th2 lines</cell_line> and clones in the presence of <protein>IFN-alpha</protein> does not induce the production of <protein>IFN-gamma</protein> .


These results suggest that activation of Stat4 , which is necessary for the differentiation of naive T cells into polarized Th1 cells , is not sufficient to induce phenotype reversal of human Th2 cells .

These results suggest that activation of <protein>Stat4</protein> , which is necessary for the differentiation of <cell_type>naive T cells</cell_type> into polarized <cell_type>Th1 cells</cell_type> , is not sufficient to induce phenotype reversal of <cell_type>human Th2 cells</cell_type> .


Molecular cloning of FKHRL1P2 , a member of the developmentally regulated fork head domain transcription factor family .

Molecular cloning of <protein>FKHRL1P2</protein> , a member of the developmentally regulated <protein>fork head domain transcription factor family</protein> .


Here we report the expression of a fork head domain protein in human T helper cells .

Here we report the expression of a <protein>fork head domain protein</protein> in <cell_type>human T helper cells</cell_type> .


We cloned and characterized a fork head cDNA from human T helper cell mRNA using differential display RT-PCR .

We cloned and characterized a <dna>fork head cDNA</dna> from <rna>human T helper cell mRNA</rna> using differential display RT-PCR .


The cDNA contains a 546-nucleotide ( nt ) open reading frame ( ORF ) that codes for the carboxyl-terminal 180 amino acids ( aa ) of the recently identified fkhrl1 gene .

The cDNA contains a <dna>546-nucleotide ( nt ) open reading frame</dna> ( <dna>ORF</dna> ) that codes for the <protein>carboxyl-terminal 180 amino acids</protein> ( aa ) of the recently identified <dna>fkhrl1 gene</dna> .


This ORF does not contain the characteristic DNA-binding domain found in members of the forkhead protein family .

This <dna>ORF</dna> does not contain the characteristic <dna>DNA-binding domain</dna> found in members of the <protein>forkhead protein family</protein> .


In-vitro transcription/translation of this cDNA expressed a protein of approximately 20 kDa .

In-vitro transcription/translation of this <dna>cDNA</dna> expressed a protein of approximately 20 kDa .


We have generated antibodies that specifically immunoprecipitated the in-vitro-translated 20-kDa protein .

We have generated antibodies that specifically immunoprecipitated the <protein>in-vitro-translated 20-kDa protein</protein> .


This antibody also recognizes in human T lymphocytes a 70-kDa protein corresponding in size to that predicted for the fkhrl1 gene product .

This antibody also recognizes in <cell_type>human T lymphocytes</cell_type> a 70-kDa protein corresponding in size to that predicted for the <dna>fkhrl1 gene</dna> product .


The mRNA levels for fkhrl1 is elevated in T helper-induced lymphocytes in comparison to PHA-stimulated T lymphocytes .

The mRNA levels for <dna>fkhrl1</dna> is elevated in <cell_type>T helper-induced lymphocytes</cell_type> in comparison to <cell_line>PHA-stimulated T lymphocytes</cell_line> .


Further characterization of FKHRL1 and its related family members should shed light on the transcriptional mechanisms of this fork head gene subfamily and their role in T helper cell differentiation and regulation of cell growth .

Further characterization of <dna>FKHRL1</dna> and its related family members should shed light on the transcriptional mechanisms of this <dna>fork head gene subfamily</dna> and their role in T helper cell differentiation and regulation of cell growth .


Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism .

Inhibition of Th1 development mediated by <protein>GATA-3</protein> through an IL-4-independent mechanism .


Recently , the transcription factor GATA-3 was shown to be selectively expressed in Th2 but not Th1 cells and to augment Th2-specific cytokines .

Recently , the <protein>transcription factor</protein> <protein>GATA-3</protein> was shown to be selectively expressed in Th2 but not <cell_type>Th1 cells</cell_type> and to augment <protein>Th2-specific cytokines</protein> .


Here , we show that loss of GATA-3 expression by developing Th1 cells requires IL-12 signaling through Stat4 and does not simply result from an absence of IL-4 .

Here , we show that loss of <protein>GATA-3</protein> expression by developing <cell_type>Th1 cells</cell_type> requires <protein>IL-12</protein> signaling through <protein>Stat4</protein> and does not simply result from an absence of <protein>IL-4</protein> .


Moreover , we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokines .

Moreover , we demonstrate a novel role for <protein>GATA-3</protein> in directly repressing Th1 development distinct from its positive actions on <protein>Th2-specific cytokines</protein> .


GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling .

<protein>GATA-3</protein> inhibits <protein>Th1 cytokines</protein> by a cell-intrinsic mechanism that is not dependent on <protein>IL-4</protein> and that may involve repression of <protein>IL-12</protein> signaling .


Thus , GATA-3 expression and IL-12 signaling are mutually antagonistic , which facilitates rapid dominance of one pathway during early Th development , producing a stable divergence in cytokine profiles .

Thus , <protein>GATA-3</protein> expression and <protein>IL-12</protein> signaling are mutually antagonistic , which facilitates rapid dominance of one pathway during early Th development , producing a stable divergence in <protein>cytokine</protein> profiles .


Conserved elements containing NF-E2 and tandem GATA binding sites are required for erythroid-specific chromatin structure reorganization within the human beta-globin locus control region .

<dna>Conserved elements</dna> containing <dna>NF-E2 and tandem GATA binding sites</dna> are required for erythroid-specific chromatin structure reorganization within the <dna>human beta-globin locus control region</dna> .


Proper expression of the genes of the human beta-globin gene locus requires the associated locus control region ( LCR ) .

Proper expression of the genes of the <dna>human beta-globin gene locus</dna> requires the associated <dna>locus control region</dna> ( <dna>LCR</dna> ) .


Structurally , the LCR is defined by the presence of four domains of erythroid-specific chromatin structure .

Structurally , the <dna>LCR</dna> is defined by the presence of four domains of erythroid-specific chromatin structure .


These domains , which have been characterized as DNase I hypersensitive sites ( HSs ) , comprise the active elements of the LCR .

These domains , which have been characterized as <dna>DNase I hypersensitive sites</dna> ( <dna>HSs</dna> ) , comprise the active elements of the <dna>LCR</dna> .


The major focus of this research is to define the cis -acting elements which are required for the formation of these domains of unique chromatin structure .

The major focus of this research is to define the <dna>cis -acting elements</dna> which are required for the formation of these domains of unique chromatin structure .


Our previous investigations on the formation of LCR HS4 demonstrated that NF-E2 and tandem , inverted GATA binding sites are required for the formation of the native HS .

Our previous investigations on the formation of <dna>LCR HS4</dna> demonstrated that <dna>NF-E2 and tandem , inverted GATA binding sites</dna> are required for the formation of the <dna>native HS</dna> .


Similarly arranged NF-E2 and tandem GATA sites are present within the core regions of the other human LCR HSs and are evolutionarily conserved .

Similarly arranged <dna>NF-E2 and tandem GATA sites</dna> are present within the <dna>core regions</dna> of the other <dna>human LCR HSs</dna> and are evolutionarily conserved .


Using site-directed mutagenesis of human HSs 2 and 3 we have tested the hypothesis that these NF-E2 and GATA sites are common requirements for the formation of all LCR HSs .

Using site-directed mutagenesis of <dna>human HSs 2 and 3</dna> we have tested the hypothesis that these <dna>NF-E2 and GATA sites</dna> are common requirements for the formation of all <dna>LCR HSs</dna> .


We find that mutation of these elements , and particularly the GATA elements , results in a decrease or complete loss of DNase I hypersensitivity .

We find that mutation of these elements , and particularly the <dna>GATA elements</dna> , results in a decrease or complete loss of <protein>DNase I</protein> hypersensitivity .


These data imply the presence of common structural elements within the core of each LCR HS which are required for erythroid-specific chromatin structure reorganization .

These data imply the presence of common structural elements within the core of each <dna>LCR HS</dna> which are required for erythroid-specific chromatin structure reorganization .


Cloning of ARE-containing genes by AU-motif-directed display .

Cloning of <dna>ARE-containing genes</dna> by AU-motif-directed display .


A procedure suitable for cloning labile mRNAs that contain AU motifs is presented ( AU-DD ) .

A procedure suitable for <rna>cloning labile mRNAs</rna> that contain AU motifs is presented ( AU-DD ) .


These motifs are regulatory sequences within the so-called AU-rich elements ( AREs ) often found in 3 ' untranslated regions of genes such as cytokines , proto-oncogenes , and transcription factors .

These motifs are <dna>regulatory sequences</dna> within the so-called <dna>AU-rich elements</dna> ( <dna>AREs</dna> ) often found in <dna>3 ' untranslated regions</dna> of genes such as <protein>cytokines</protein> , <dna>proto-oncogenes</dna> , and <protein>transcription factors</protein> .


AU-DD is an AU-motif-directed differential display that permits the identification of ARE-containing genes differentially expressed after cell activation .

<dna>AU-DD</dna> is an <dna>AU-motif-directed differential display</dna> that permits the identification of <dna>ARE-containing genes</dna> differentially expressed after cell activation .


It has been applied to peripheral blood monocytes and a T cell clone to isolate 59 cDNA fragments associated to activation .

It has been applied to <cell_type>peripheral blood monocytes</cell_type> and a <cell_line>T cell clone</cell_line> to isolate <dna>59 cDNA fragments</dna> associated to activation .


Fourteen percent of isolated fragments belong to already known genes that certainly are cytokines and transduction/transcription factors .

Fourteen percent of isolated fragments belong to already known genes that certainly are <protein>cytokines</protein> and <protein>transduction/transcription factors</protein> .


The remaining 86 % correspond to unknown genes of which 92 % have been confirmed to be differentially expressed .

The remaining 86 % correspond to unknown <dna>genes</dna> of which 92 % have been confirmed to be differentially expressed .


These data demonstrate the efficiency of the system and support the notion that numerous genes falling into those categories remain unidentified and that they can be cloned by this method .

These data demonstrate the efficiency of the system and support the notion that numerous <dna>genes</dna> falling into those categories remain unidentified and that they can be cloned by this method .


Copyright 1998 Academic Press .


Transcription factor NF-kappaB regulation of renal fibrosis during ureteral obstruction .

Transcription factor <protein>NF-kappaB</protein> regulation of renal fibrosis during ureteral obstruction .


Irrespective of the etiology , many kidney diseases result in inflammation and fibrosis of the tubulointerstitium , with the subsequent loss of renal function .


To initiate any disease process or for any disease process to progress , there must be changes in the transcription of genes within the affected tissue .


The nuclear factor-kappa B ( NF-kappaB ) family of transcription factors regulates genes involved in inflammation , cell proliferation , and cell differentiation .

The <protein>nuclear factor-kappa B ( NF-kappaB ) family</protein> of <protein>transcription factors</protein> regulates genes involved in inflammation , cell proliferation , and cell differentiation .


This review discusses the NF-kappaB transcription factor family in general and the association of NF-kappaB activation with cellular/molecular events of renal inflammation and fibrosis

This review discusses the <protein>NF-kappaB transcription factor family</protein> in general and the association of <protein>NF-kappaB</protein> activation with cellular/molecular events of renal inflammation and fibrosis


Expression of transcription factors during sodium phenylacetate induced erythroid differentiation in K562 cells .

Expression of <protein>transcription factors</protein> during sodium phenylacetate induced erythroid differentiation in <cell_line>K562 cells</cell_line> .


During 15 days of treatment of K562 cells with sodium phenylacetate , we observed an increase in the cellular hemoglobin concentration with a similar increase in the expression of gamma-globin mRNA .

During 15 days of treatment of <cell_line>K562 cells</cell_line> with sodium phenylacetate , we observed an increase in the cellular <protein>hemoglobin</protein> concentration with a similar increase in the expression of <rna>gamma-globin mRNA</rna> .


Morphological studies demonstrated characteristic features of erythroid differentiation and maturation .


At the same time there was no change in the level of expression of the cell surface antigenes CD33 , CD34 , CD45 , CD71 and glycophorin A .

At the same time there was no change in the level of expression of the <protein>cell surface antigenes</protein> <protein>CD33</protein> , <protein>CD34</protein> , <protein>CD45</protein> , <protein>CD71</protein> and <protein>glycophorin A</protein> .


Likewise , the level of expression of the erythroid transcription factors GATA-1 , GATA-2 , NF-E2 , SCL and RBTN2 , all expressed in untreated K562 cells , did not increase during sodium phenylacetate induced erythroid differentiation .

Likewise , the level of expression of the <protein>erythroid transcription factors</protein> <protein>GATA-1</protein> , <protein>GATA-2</protein> , <protein>NF-E2</protein> , <protein>SCL</protein> and <protein>RBTN2</protein> , all expressed in untreated <cell_line>K562 cells</cell_line> , did not increase during sodium phenylacetate induced erythroid differentiation .


The expression of the nuclear factors Evi-1 and c-myb , known to inhibit erythroid differentiation , did not decrease .

The expression of the <protein>nuclear factors</protein> <protein>Evi-1</protein> and <protein>c-myb</protein> , known to inhibit erythroid differentiation , did not decrease .


We conclude that sodium phenylacetate treatment of K562 cells increases gamma-globin mRNA and induces cell maturation as judged by morphology without affecting the expression of the erythroid transcription factors , some of which are known to be involved in the regulation of beta-like globin genes .

We conclude that sodium phenylacetate treatment of <cell_line>K562 cells</cell_line> increases <rna>gamma-globin mRNA</rna> and induces cell maturation as judged by morphology without affecting the expression of the <protein>erythroid transcription factors</protein> , some of which are known to be involved in the regulation of <dna>beta-like globin genes</dna> .


Isolation of a B-cell-specific promoter for the human class II transactivator .

Isolation of a <dna>B-cell-specific promoter</dna> for the <protein>human class II transactivator</protein> .


The class II transactivator ( CIITA ) is essential for the expression of major histocompatibility complex ( MHC ) class II antigens .

The <protein>class II transactivator</protein> ( <protein>CIITA</protein> ) is essential for the expression of <protein>major histocompatibility complex ( MHC ) class II antigens</protein> .


The tissular patterns of CIITA and MHC class II gene expression are tightly correlated : CIITA mRNA is highly expressed in B cells , and is induced by interferon gamma ( IFN-gamma ) in macrophage and epithelial cell lines .

The tissular patterns of CIITA and MHC class II gene expression are tightly correlated : <rna>CIITA mRNA</rna> is highly expressed in <cell_type>B cells</cell_type> , and is induced by <protein>interferon gamma</protein> ( <protein>IFN-gamma</protein> ) in <cell_line>macrophage and epithelial cell lines</cell_line> .


We first isolated two overlapping cosmids encoding human CIITA which , when co-transfected , are able to restore MHC class II expression in a B-lymphoblastoid cell line ( B-LCL ) defective for CIITA .

We first isolated two overlapping <dna>cosmids</dna> encoding <protein>human CIITA</protein> which , when co-transfected , are able to restore <protein>MHC class II</protein> expression in a <cell_line>B-lymphoblastoid cell line</cell_line> ( <cell_line>B-LCL</cell_line> ) defective for <protein>CIITA</protein> .


Subsequently , a 1.8 kilobase ( kb ) fragment of the CIITA promoter was isolated and sequenced .

Subsequently , a <dna>1.8 kilobase ( kb ) fragment</dna> of the <dna>CIITA promoter</dna> was isolated and sequenced .


A motif presenting a strong similarity to an initiator was detected , as well as putative binding sites for Sp1 , GATA-2 , LyF-1 , ets-1 , AP1 , and MZF1 transcription factors , and two GAS motifs .

A motif presenting a strong similarity to an initiator was detected , as well as <dna>putative binding sites</dna> for <protein>Sp1</protein> , <protein>GATA-2</protein> , <protein>LyF-1</protein> , <protein>ets-1</protein> , <protein>AP1</protein> , and <protein>MZF1</protein> <protein>transcription factors</protein> , and two <dna>GAS motifs</dna> .


When introduced in front of a luciferase reporter gene , this promoter is able to direct a high luciferase activity in a human B-LCL .

When introduced in front of a <dna>luciferase reporter gene</dna> , this promoter is able to direct a high <protein>luciferase</protein> activity in a <cell_line>human B-LCL</cell_line> .


In contrast , luciferase expression was not stimulated after IFN-gamma treatment when the construct was transfected in macrophage or in epithelial cell lines .

In contrast , <protein>luciferase</protein> expression was not stimulated after <protein>IFN-gamma</protein> treatment when the construct was transfected in macrophage or in <cell_line>epithelial cell lines</cell_line> .


However , an induction of the human CIITA gene was observed in mouse macrophage and fibrosarcoma cell lines , when the cells were transfected with a cosmid containing the human CIITA gene , but lacking the 1.8 kb promoter described above .

However , an induction of the <dna>human CIITA gene</dna> was observed in <cell_line>mouse macrophage and fibrosarcoma cell lines</cell_line> , when the cells were transfected with a <dna>cosmid</dna> containing the <dna>human CIITA gene</dna> , but lacking the <dna>1.8 kb promoter</dna> described above .


Taken together , these data suggest the existence of an intragenic promoter driving an IFN-gamma -inducible expression of CIITA .

Taken together , these data suggest the existence of an intragenic promoter driving an <protein>IFN-gamma</protein> -inducible expression of <protein>CIITA</protein> .


Phenotypic and functional studies of leukocytes in human endometrium and endometriosis .

Phenotypic and functional studies of <cell_type>leukocytes</cell_type> in human endometrium and endometriosis .


The aetiology of endometriosis , a common and disabling disorder , is presently unknown , although immune dysfunction could allow ectopic endometrial fragments to survive outside the uterine cavity .


These studies investigate the relationship between leukocyte populations , steroid hormone receptor expression , proliferative activity , bcl-2 expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle .

These studies investigate the relationship between <cell_type>leukocyte populations</cell_type> , <protein>steroid hormone receptor</protein> expression , proliferative activity , <protein>bcl-2</protein> expression and apoptosis in eutopic and ectopic endometrium from women with endometriosis or adenomyosis at different phases of the menstrual cycle .


Significantly increased oestrogen receptor expression , bcl-2 expression and numbers of CD8+ leukocytes were found in ectopic compared with eutopic endometrium in endometriosis , and CD56+ endometrial granulated lymphocytes ( eGLs ) were significantly reduced in ectopic endometrium .

Significantly increased <protein>oestrogen receptor</protein> expression , <protein>bcl-2</protein> expression and numbers of CD8+ <cell_type>leukocytes</cell_type> were found in ectopic compared with eutopic endometrium in endometriosis , and CD56+ endometrial granulated lymphocytes ( eGLs ) were significantly reduced in ectopic endometrium .


Apoptotic cells were rarely found in control and subject endometria .

<cell_type>Apoptotic cells</cell_type> were rarely found in control and subject endometria .


In contrast with endometriosis , adenomyotic lesions showed identical steroid hormone receptor expression , proliferative activity , bcl-2 expression and leukocyte subpopulations to eutopic endometrium , indicating different aetiologies for these disorders .

In contrast with endometriosis , adenomyotic lesions showed identical <protein>steroid hormone receptor</protein> expression , proliferative activity , <protein>bcl-2</protein> expression and leukocyte subpopulations to eutopic endometrium , indicating different aetiologies for these disorders .


The unusual CD56+ CD16- eGLs present in large numbers in late secretory phase eutopic endometrium were highly purified ( > 98 % ) by immunomagnetic separation .

The unusual <cell_type>CD56+ CD16- eGLs</cell_type> present in large numbers in late secretory phase eutopic endometrium were highly purified ( > 98 % ) by immunomagnetic separation .


Except for a negligible cytotoxic activity of eGLs from early proliferative samples , cytotoxic activity of eGLs from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood , predominantly CD56+ CD16+ natural killer cells .

Except for a negligible cytotoxic activity of <cell_type>eGLs</cell_type> from early proliferative samples , cytotoxic activity of <cell_type>eGLs</cell_type> from non-pregnant endometrium during the menstrual cycle was comparable with those in peripheral blood , predominantly <cell_type>CD56+ CD16+ natural killer cells</cell_type> .


eGLs from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml interleukin-2 over 48-h and 120-h time courses .

<cell_type>eGLs</cell_type> from non-pregnant endometrium and early pregnancy showed a variable proliferative response to 5 and 100 U/ml <protein>interleukin-2</protein> over 48-h and 120-h time courses .


eGLs are evidently functionally important in the eutopic endometrium .

<cell_type>eGLs</cell_type> are evidently functionally important in the eutopic endometrium .


Their absence in endometriotic lesions together with increased CD+8 T-cell numbers and increased oestrogen receptor and bcl-2 expression may have significant effects on the development and progression of endometriosis .

Their absence in endometriotic lesions together with increased <cell_type>CD+8 T-cell</cell_type> numbers and increased <protein>oestrogen receptor</protein> and <protein>bcl-2</protein> expression may have significant effects on the development and progression of endometriosis .


Regulation of interleukin-1beta transcription by Epstein-Barr virus involves a number of latent proteins via their interaction with RBP .

Regulation of <protein>interleukin-1beta</protein> transcription by Epstein-Barr virus involves a number of <protein>latent proteins</protein> via their interaction with <protein>RBP</protein> .


Epstein-Barr virus ( EBV ) infects B cells , resulting in the outgrowth of immortalised lymphoblastoid cell lines ( LCLs ) .

Epstein-Barr virus ( EBV ) infects <cell_type>B cells</cell_type> , resulting in the outgrowth of <cell_line>immortalised lymphoblastoid cell lines</cell_line> ( <cell_line>LCLs</cell_line> ) .


Here , we demonstrate through the use of intracellular staining that interleukin-1beta ( IL-1beta ) is expressed in LCLs and investigate the influence of the individual latent proteins on the expression of IL-1beta .

Here , we demonstrate through the use of intracellular staining that <protein>interleukin-1beta</protein> ( <protein>IL-1beta</protein> ) is expressed in <cell_line>LCLs</cell_line> and investigate the influence of the individual <protein>latent proteins</protein> on the expression of <protein>IL-1beta</protein> .


Using RT-PCR , IL-1beta was shown to be up-regulated in EBV-transformed LCLs as well as in group III Burkitt 's lymphoma ( BL ) cell lines , compared with group I BL cell lines .

Using RT-PCR , <protein>IL-1beta</protein> was shown to be up-regulated in <cell_line>EBV-transformed LCLs</cell_line> as well as in <cell_line>group III Burkitt 's lymphoma ( BL ) cell lines</cell_line> , compared with <cell_line>group I BL cell lines</cell_line> .


The up-regulation of IL-1beta message could be mediated by the latent membrane protein-1 , EBV nuclear proteins 2 , 3 , 4 , and 6 genes .

The up-regulation of <protein>IL-1beta</protein> message could be mediated by the <protein>latent membrane protein-1</protein> , <dna>EBV nuclear proteins 2 , 3 , 4 , and 6 genes</dna> .


Electrophoretic mobility shift assays ( EMSAs ) demonstrated that the -300 region of the IL-1beta promoter , which contains a nuclear factor-kappaB ( NF-kappaB ) binding site , contained a functional RBP binding site .

Electrophoretic mobility shift assays ( EMSAs ) demonstrated that the -300 region of the <protein>IL-1beta</protein> promoter , which contains a <dna>nuclear factor-kappaB ( NF-kappaB ) binding site</dna> , contained a <dna>functional RBP binding site</dna> .


Binding of RBP to this site could be inhibited by addition of EBV nuclear proteins 3 and 6 , suggesting that these proteins displace RBP from its recognition sequence , removing transcriptional repression and allowing gene transcription to occur .

Binding of RBP to this site could be inhibited by addition of <protein>EBV nuclear proteins 3 and 6</protein> , suggesting that these proteins displace <protein>RBP</protein> from its <dna>recognition sequence</dna> , removing transcriptional repression and allowing gene transcription to occur .


In group I BL cells , containing low levels of NF-kappaB , only RBP binding was observed in EMSAs , whereas NF-kappaB binding could be demonstrated in EBV-transformed B cell lines containing high levels of activated NF-kappaB .

In <cell_line>group I BL cells</cell_line> , containing low levels of <protein>NF-kappaB</protein> , only <protein>RBP</protein> binding was observed in EMSAs , whereas <protein>NF-kappaB</protein> binding could be demonstrated in <cell_line>EBV-transformed B cell lines</cell_line> containing high levels of activated <protein>NF-kappaB</protein> .


In addition , the expression of latent membrane protein-1 led to activation of NF-kappaB that was capable of binding the IL-1beta promoter .

In addition , the expression of <protein>latent membrane protein-1</protein> led to activation of <protein>NF-kappaB</protein> that was capable of binding the <dna>IL-1beta promoter</dna> .


The study demonstrates that EBV can up-regulate IL-1beta expression , possibly by using RBP , NF-kappaB , or both .

The study demonstrates that EBV can up-regulate <protein>IL-1beta</protein> expression , possibly by using <protein>RBP</protein> , <protein>NF-kappaB</protein> , or both .


Copyright 1998 Academic Press .


CD27 /CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells .

<protein>CD27</protein> /CD70 interaction augments <protein>IgE</protein> secretion by promoting the differentiation of <cell_type>memory B cells</cell_type> into <cell_type>plasma cells</cell_type> .


The induction of IgE switching in B cells requires several signals given by cytokines and cell contact-delivered signals .

The induction of <protein>IgE</protein> switching in <cell_type>B cells</cell_type> requires several signals given by <protein>cytokines</protein> and cell contact-delivered signals .


Here , we investigated the role of CD27 /CD70 interaction in B cell IgE synthesis .

Here , we investigated the role of <protein>CD27</protein> /CD70 interaction in B cell <protein>IgE</protein> synthesis .


The addition of CD27 ligand ( CD70 ) transfectants to B cell cultures increased the IgE synthesis synergistically in the presence of IL-4 plus anti-CD40 mAb ( anti-CD40 ) .

The addition of CD27 ligand ( CD70 ) transfectants to <cell_line>B cell cultures</cell_line> increased the <protein>IgE</protein> synthesis synergistically in the presence of <protein>IL-4</protein> plus <protein>anti-CD40 mAb</protein> ( <protein>anti-CD40</protein> ) .


The effect of CD70 transfectants was dose dependent and was completely blocked by anti-CD70 mAb .

The effect of <cell_line>CD70 transfectants</cell_line> was dose dependent and was completely blocked by <protein>anti-CD70 mAb .</protein>


CD27+ B cells had the ability to produce IgE , which was increased by contact with CD70 transfectants , whereas CD27- B cells did not produce IgE .

<cell_type>CD27+ B cells</cell_type> had the ability to produce <protein>IgE</protein> , which was increased by contact with CD70 transfectants , whereas CD27- B cells did not produce <protein>IgE</protein> .


CD27 /CD70 interaction enhanced B cell proliferation in the presence of IL-4 or IL-4 plus anti-CD40 .

<protein>CD27</protein> /CD70 interaction enhanced <cell_type>B cell</cell_type> proliferation in the presence of <protein>IL-4</protein> or <protein>IL-4</protein> plus <protein>anti-CD40</protein> .


The augmentation of B cell proliferation by CD70 transfectants was apparent in CD27+ B cells , but was mild in CD27- B cells .

The augmentation of B cell proliferation by CD70 transfectants was apparent in <cell_type>CD27+ B cells</cell_type> , but was mild in <cell_type>CD27- B cells</cell_type> .


The helper activity for IgE synthesis by the CD27 /CD70 interaction did not contribute to the enhancement of germline epsilon transcripts .

The helper activity for <protein>IgE</protein> synthesis by the <protein>CD27</protein> /CD70 interaction did not contribute to the enhancement of <rna>germline epsilon transcripts</rna> .


Flow cytometric and morphological analyses demonstrated that the addition of CD70 transfectants to B cell cultures remarkably promoted differentiation into plasma cells in the presence of IL-4 and CD40 signaling .

Flow cytometric and morphological analyses demonstrated that the addition of CD70 transfectants to <cell_line>B cell cultures</cell_line> remarkably promoted differentiation into <cell_type>plasma cells</cell_type> in the presence of <protein>IL-4</protein> and <protein>CD40</protein> signaling .


Finally , CD27 cross-linking resulted in the up-regulation of positive regulatory domain I-binding factor-1 .

Finally , <protein>CD27</protein> cross-linking resulted in the up-regulation of <protein>positive regulatory domain I-binding factor-1</protein> .


Taken together , our findings indicate that signaling via CD27 on B cells induces IgE synthesis , in cooperation with IL-4 and CD40 signaling , by promoting the generation of plasma cells through up-regulation of positive regulatory domain I-binding factor-1 .

Taken together , our findings indicate that signaling via <protein>CD27</protein> on <cell_type>B cells</cell_type> induces <protein>IgE</protein> synthesis , in cooperation with <protein>IL-4</protein> and <protein>CD40</protein> signaling , by promoting the generation of <cell_type>plasma cells</cell_type> through up-regulation of <protein>positive regulatory domain I-binding factor-1</protein> .


Human immunodeficiency virus type-1 transcription : role of the 5'-untranslated leader region ( review ) .


Human immunodeficiency virus type-1 ( HIV-1 ) transcription is dependent on the interaction of host-cell transcription factors with cis-regulatory DNA elements within the viral long terminal repeat ( LTR ) .

Human immunodeficiency virus type-1 ( HIV-1 ) transcription is dependent on the interaction of <protein>host-cell transcription factors</protein> with <dna>cis-regulatory DNA elements</dna> within the <dna>viral long terminal repeat</dna> ( <dna>LTR</dna> ) .


Much attention has focused on the series of sequence elements upstream of the transcriptional initiation site in the U3 region of the LTR including the Sp1 and NF-kappaB binding sites .

Much attention has focused on the series of sequence elements upstream of the <dna>transcriptional initiation site</dna> in the <dna>U3 region</dna> of the <dna>LTR</dna> including the <protein>Sp1</protein> and <protein>NF-kappaB</protein> <dna>binding sites</dna> .


Recent studies , however , demonstrate that the transcribed 5'-untranslated leader region ( 5'-UTR ) also contains important transcriptional elements .

Recent studies , however , demonstrate that the transcribed <dna>5'-untranslated leader region</dna> ( <dna>5'-UTR</dna> ) also contains important <dna>transcriptional elements</dna> .


These regulatory elements situated downstream of transcription interact with constitutive and inducible transcription factors , mediate transmission of cellular activation signals , and are important for efficient HIV-1 transcription and replication .

These <dna>regulatory elements</dna> situated downstream of transcription interact with constitutive and inducible <protein>transcription factors</protein> , mediate transmission of cellular activation signals , and are important for efficient HIV-1 transcription and replication .


The 5'-UTR contains binding sites for the transcription factors AP-1 , NF-kappaB , NF-AT , IRF , and Sp1 .

The <dna>5'-UTR</dna> contains <dna>binding sites</dna> for the <protein>transcription factors</protein> AP-1 , <protein>NF-kappaB</protein> , <protein>NF-AT</protein> , <protein>IRF</protein> , and <protein>Sp1</protein> .


Mutations in these binding sites can interfere with the viral response to cell activation signals , decrease LTR transcription , and inhibit viral replication .

Mutations in these <dna>binding sites</dna> can interfere with the viral response to cell activation signals , decrease <dna>LTR</dna> transcription , and inhibit viral replication .


The 5'-UTR also interacts with a specific nucleosome that is rapidly displaced during transcriptional activation of the latent provirus .

The <dna>5'-UTR</dna> also interacts with a specific <protein>nucleosome</protein> that is rapidly displaced during transcriptional activation of the latent provirus .


We propose that the inducible transcription factor binding sites in the 5'-UTR comprise a downstream enhancer domain that can function independent of , or in concert with , the LTR promoter to rapidly increase latent proviral transcription in response to cell activation signals .

We propose that the <dna>inducible transcription factor binding sites</dna> in the <dna>5'-UTR</dna> comprise a <dna>downstream enhancer domain</dna> that can function independent of , or in concert with , the <dna>LTR promoter</dna> to rapidly increase latent proviral transcription in response to cell activation signals .


In this review , we describe the host-cell transcription factors that interact with the 5'-UTR and discuss their role in the transcriptional regulation of HIV-1 gene expression .

In this review , we describe the <protein>host-cell transcription factors</protein> that interact with the <dna>5'-UTR</dna> and discuss their role in the transcriptional regulation of HIV-1 gene expression .


Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76 .

Regulation of PAK activation and the T cell cytoskeleton by the <protein>linker protein</protein> <protein>SLP-76</protein> .


Tyrosine phosphorylation of linker proteins enables the T cell antigen receptor ( TCR ) -associated protein tyrosine kinases to phosphorylate and regulate effector molecules that generate second messengers .

Tyrosine phosphorylation of <protein>linker proteins</protein> enables the <protein>T cell antigen receptor ( TCR ) -associated protein tyrosine kinases</protein> to phosphorylate and regulate <protein>effector molecules</protein> that generate <protein>second messengers</protein> .


We demonstrate here that the SLP-76 linker protein interacts with both nck , an adaptor protein , and Vav , a guanine nucleotide exchange factor for Rho-family GTPases .

We demonstrate here that the <protein>SLP-76</protein> linker protein interacts with both <protein>nck</protein> , an <protein>adaptor protein</protein> , and <protein>Vav</protein> , a <protein>guanine nucleotide exchange factor</protein> for <protein>Rho-family GTPases</protein> .


The assembly of this tri-molecular complex permits the activated Rho-family GTPases to regulate target effectors that interact through nck .

The assembly of this <protein>tri-molecular complex</protein> permits the activated <protein>Rho-family GTPases</protein> to regulate target effectors that interact through <protein>nck</protein> .


In turn , assembly of this complex mediates the enzymatic activation of the p21-activated protein kinase 1 and facilitates actin polymerization .

In turn , assembly of this complex mediates the enzymatic activation of the <protein>p21-activated protein kinase 1</protein> and facilitates <protein>actin</protein> polymerization .


Hence , phosphorylation of linker proteins not only bridges the TCR-associated PTK , ZAP-70 , with downstream effector proteins , but also provides a scaffold to integrate distinct signaling complexes to regulate T cell function .

Hence , phosphorylation of <protein>linker proteins</protein> not only bridges the <protein>TCR-associated PTK</protein> , <protein>ZAP-70</protein> , with downstream effector proteins , but also provides a scaffold to integrate distinct <protein>signaling complexes</protein> to regulate <cell_type>T cell</cell_type> function .


Interleukin-12 expression in B cells by transformation with Epstein-Barr virus .

<protein>Interleukin-12</protein> expression in <cell_type>B cells</cell_type> by transformation with Epstein-Barr virus .


Although interleukin ( IL ) -12 was originally purified from an Epstein-Barr ( EBV ) -transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested , no study has reported whether EBV infection is directly linked to IL-12 expression .

Although <protein>interleukin ( IL ) -12</protein> was originally purified from an <cell_line>Epstein-Barr ( EBV ) -transformed B cell line</cell_line> and the high correlation of EBV infection and <protein>IL-12</protein> expression has been suggested , no study has reported whether EBV infection is directly linked to <protein>IL-12</protein> expression .


To address this issue , we have investigated IL-12 expression in B cells during in vitro transformation with EBV .

To address this issue , we have investigated <protein>IL-12</protein> expression in <cell_type>B cells</cell_type> during in vitro transformation with EBV .


Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV , coincident with the expression of latent membrane protein 1 ( LMP1 ) of EBV .

<cell_type>Human peripheral B cells</cell_type> became capable of constitutively producing p40 by in vitro transformation with EBV , coincident with the expression of <protein>latent membrane protein 1</protein> ( <protein>LMP1</protein> ) of EBV .


These B cells expressed p40 and p35 mRNA , and phorbol myristate acetate ( PMA ) stimulation strongly enhanced p40 and p70 production .

These <cell_type>B cells</cell_type> expressed <rna>p40 and p35 mRNA</rna> , and phorbol myristate acetate ( PMA ) stimulation strongly enhanced p40 and p70 production .


Furthermore , transfection with LMP1 expression vector into a human B lymphoma cell line , Daudi , led to p40 production with nuclear factor ( NF ) -kappaB activation .

Furthermore , transfection with <dna>LMP1 expression vector</dna> into a <cell_line>human B lymphoma cell line</cell_line> , <cell_line>Daudi</cell_line> , led to <protein>p40</protein> production with <protein>nuclear factor ( NF ) -kappaB</protein> activation .


These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression .

These results suggest that transformation of <cell_type>primary B cells</cell_type> with EBV induces <protein>IL-12</protein> expression potentially through <protein>LMP1</protein> expression .


Copyright 1998 Academic Press .


The human gene encoding the lectin-type oxidized LDL receptor ( OLR1 ) is a novel member of the natural killer gene complex with a unique expression profile .

The <dna>human gene</dna> encoding the <protein>lectin-type oxidized LDL receptor</protein> ( <protein>OLR1</protein> ) is a novel member of the <protein>natural killer gene complex</protein> with a unique expression profile .


LOX-1 is an endothelial receptor for oxidized low-density lipoprotein that plays essential roles in atherogenesis .

<protein>LOX-1</protein> is an <protein>endothelial receptor</protein> for <protein>oxidized low-density lipoprotein</protein> that plays essential roles in atherogenesis .


LOX-1 has the highest homology with C-type lectin receptors expressed on natural killer cells .

<protein>LOX-1</protein> has the highest homology with <protein>C-type lectin receptors</protein> expressed on <cell_type>natural killer cells</cell_type> .


In the present study , we cloned and characterized the human LOX-1 gene ( HGMW-approved symbol OLR1 ) .

In the present study , we cloned and characterized the <dna>human LOX-1 gene</dna> ( <protein>HGMW-approved symbol OLR1</protein> ) .


The gene structure of LOX-1 resembles that of the natural killer cell receptors .

The gene structure of <protein>LOX-1</protein> resembles that of the <protein>natural killer cell receptors</protein> .


Fluorescence in situ hybridization and analyses of a yeast artificial chromosome contig revealed that the human LOX-1 gene is located in the natural killer gene complex on chromosome 12p12-p13 , where the genes of the natural killer cell receptors cluster .

Fluorescence in situ hybridization and analyses of a yeast artificial chromosome contig revealed that the <dna>human LOX-1 gene</dna> is located in the <protein>natural killer gene complex</protein> on <dna>chromosome 12p12-p13</dna> , where the genes of the <protein>natural killer cell receptors</protein> cluster .


In contrast , the expression pattern of LOX-1 is different from that of the natural killer cell receptors ; LOX-1 is expressed in vascular-rich organs , but not in lymphocytes .

In contrast , the expression pattern of <protein>LOX-1</protein> is different from that of the <protein>natural killer cell receptors</protein> ; <protein>LOX-1</protein> is expressed in vascular-rich organs , but not in <cell_type>lymphocytes</cell_type> .


A 1753-bp fragment of the 5 ' flanking region of the LOX-1 gene had a functional promoter activity .

A <dna>1753-bp fragment</dna> of the <dna>5 ' flanking region</dna> of the <dna>LOX-1 gene</dna> had a functional promoter activity .


This region contains binding sites for several transcription factors , including the STAT family and NF-IL6 , and the expression of LOX-1 was upregulated by several cytokines .

This region contains <dna>binding sites</dna> for several <protein>transcription factors</protein> , including the <protein>STAT family</protein> and <protein>NF-IL6</protein> , and the expression of <protein>LOX-1</protein> was upregulated by several <protein>cytokines</protein> .


These results demonstrate that the human LOX-1 gene is a new member of the natural killer gene complex with a unique expression profile .

These results demonstrate that the <dna>human LOX-1 gene</dna> is a new member of the <protein>natural killer gene complex</protein> with a unique expression profile .


Transcriptional regulation of the beta-casein gene by cytokines : cross-talk between STAT5 and other signaling molecules .

Transcriptional regulation of the <dna>beta-casein gene</dna> by <protein>cytokines</protein> : cross-talk between <protein>STAT5</protein> and other <protein>signaling molecules</protein> .


The beta-casein promoter has been widely used to monitor the activation of STAT ( signal transducer and activator of transcription ) 5 since STAT5 was originally found as a mediator of PRL-inducible beta-casein expression .

The <dna>beta-casein promoter</dna> has been widely used to monitor the activation of <protein>STAT ( signal transducer and activator of transcription ) 5</protein> since <protein>STAT5</protein> was originally found as a mediator of PRL-inducible <protein>beta-casein</protein> expression .


However , not only is expression of the beta-casein gene regulated by STAT5 but it is also affected by other molecules such as glucocorticoid and Ras .

However , not only is expression of the <dna>beta-casein gene</dna> regulated by <protein>STAT5</protein> but it is also affected by other molecules such as glucocorticoid and <protein>Ras</protein> .


In this report , we describe the transcriptional regulation of the beta-casein gene by cytokines in T cells .

In this report , we describe the transcriptional regulation of the <dna>beta-casein gene</dna> by <protein>cytokines</protein> in <cell_type>T cells</cell_type> .


We have found that the beta-casein gene is expressed in a cytotoxic T cell line , CTLL-2 , in response to interleukin-2 ( IL-2 ) , which activates STAT5 .

We have found that the <dna>beta-casein gene</dna> is expressed in a <cell_line>cytotoxic T cell line</cell_line> , <cell_line>CTLL-2</cell_line> , in response to <protein>interleukin-2</protein> ( <protein>IL-2</protein> ) , which activates <protein>STAT5</protein> .


While IL-4 does not activate STAT5 , it induces expression of STAT5-regulated genes in CTLL-2 , i.e . beta-casein , a cytokine-inducible SH2-containing protein ( CIS ) , and oncostatin M ( OSM ) , suggesting that STAT6 activated by IL-4 substitutes for the function of STAT5 in T cells .

While <protein>IL-4</protein> does not activate <protein>STAT5</protein> , it induces expression of <dna>STAT5-regulated genes</dna> in <cell_line>CTLL-2</cell_line> , i.e . <protein>beta-casein</protein> , a <protein>cytokine-inducible SH2-containing protein</protein> ( <protein>CIS</protein> ) , and <protein>oncostatin M</protein> ( <protein>OSM</protein> ) , suggesting that STAT6 activated by <protein>IL-4</protein> substitutes for the function of <protein>STAT5</protein> in <cell_type>T cells</cell_type> .


IL-2 -induced beta-casein expression was enhanced by dexamethasone , and this synergistic effect of Dexamethasone requires the sequence between -155 and -193 in the beta-casein promoter .

<protein>IL-2</protein> -induced <protein>beta-casein</protein> expression was enhanced by dexamethasone , and this synergistic effect of Dexamethasone requires the sequence between <dna>-155 and -193</dna> in the <dna>beta-casein promoter</dna> .


Coincidentally , a deletion of this region enhanced the IL-2 -induced expression of beta-casein .

Coincidentally , a deletion of this region enhanced the <protein>IL-2</protein> -induced expression of <protein>beta-casein</protein> .


Expression of an active form of Ras , Ras ( G12V ) , suppressed the IL-2 -induced beta-casein and OSM gene expression , and the negative effect of Ras is mediated by the region between -105 and -193 in the beta-casein promoter .

Expression of an active form of <protein>Ras</protein> , <protein>Ras ( G12V )</protein> , suppressed the <protein>IL-2</protein> -induced <protein>beta-casein</protein> and <protein>OSM</protein> gene expression , and the negative effect of <protein>Ras</protein> is mediated by the region between <dna>-105 and -193</dna> in the <dna>beta-casein promoter</dna> .


In apparent contradiction , expression of a dominant negative form of Ras , RasN17 , also inhibited IL-2 -induced activation of the promoter containing the minimal beta-casein STAT5 element as well as the promoters of CIS and OSM .

In apparent contradiction , expression of a dominant negative form of <protein>Ras</protein> , <protein>RasN17</protein> , also inhibited <protein>IL-2</protein> -induced activation of the promoter containing the minimal <dna>beta-casein STAT5 element</dna> as well as the promoters of <protein>CIS</protein> and <protein>OSM</protein> .


In addition , Ras ( G12V ) complemented signaling by an erythropoietin receptor mutant defective in Ras activation and augmented the activation of the beta-casein promoter by the mutant erythropoietin receptor signaling , suggesting a possible role of Ras in Stat5 -mediated gene expression .

In addition , <protein>Ras ( G12V )</protein> complemented signaling by an <protein>erythropoietin receptor mutant</protein> defective in <protein>Ras</protein> activation and augmented the activation of the <dna>beta-casein promoter</dna> by the <protein>mutant erythropoietin receptor</protein> signaling , suggesting a possible role of <protein>Ras</protein> in <protein>Stat5</protein> -mediated gene expression .


These results collectively reveal a complex interaction of STAT5 with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals

These results collectively reveal a complex interaction of <protein>STAT5</protein> with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals


GATA-3 represses gp91phox gene expression in eosinophil-committed HL-60-C15 cells .

<protein>GATA-3</protein> represses <dna>gp91phox gene</dna> expression in <cell_line>eosinophil-committed HL-60-C15 cells</cell_line> .


To study the regulatory mechanism of gp91phox gene expression in eosinophils , we transiently transfected eosinophil-committed HL-60-C15 cells with gp91phox promoter constructs , and identified a negative element from bp -267 to -246 of the gp91phox gene , the deletion of which caused an 83 % increase in promoter activity .

To study the regulatory mechanism of <dna>gp91phox gene</dna> expression in eosinophils , we transiently transfected <cell_line>eosinophil-committed HL-60-C15 cells</cell_line> with <dna>gp91phox promoter constructs</dna> , and identified a <dna>negative element</dna> from bp <dna>-267 to -246</dna> of the <dna>gp91phox gene</dna> , the deletion of which caused an 83 % increase in promoter activity .


Electrophoresis mobility shift assays demonstrated GATA-3 binds to the GATA consensus site from bp -256 to -250 .

Electrophoresis mobility shift assays demonstrated <protein>GATA-3</protein> binds to the <dna>GATA consensus site</dna> from bp <dna>-256 to -250 .</dna>


An 81 % increment in promoter activity was obtained when a mutation was introduced in the GATA-3 binding site of the bp -267 to +12 construct , which is comparable to that of the bp -245 to +12 construct .

An 81 % increment in promoter activity was obtained when a mutation was introduced in the <dna>GATA-3 binding site</dna> of the <dna>bp -267 to +12 construct</dna> , which is comparable to that of the <dna>bp -245 to +12 construct</dna> .


We therefore conclude that GATA-3 specifically binding to the GATA site negatively regulates the expression of the gene in HL-60-C15 cells .

We therefore conclude that <protein>GATA-3</protein> specifically binding to the <dna>GATA site</dna> negatively regulates the expression of the gene in <cell_line>HL-60-C15 cells</cell_line> .


Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells : differential signaling through CD3 and the costimulatory receptors CD2 and CD28 .

Uncoupling activation-dependent <protein>HS1</protein> phosphorylation from <protein>nuclear factor of activated T cells</protein> transcriptional activation in <cell_line>Jurkat T cells</cell_line> : differential signaling through <protein>CD3</protein> and the costimulatory receptors <protein>CD2</protein> and <protein>CD28</protein> .


CD3 , CD2 , and CD28 are functionally distinct receptors on T lymphocytes .

<protein>CD3</protein> , <protein>CD2</protein> , and <protein>CD28</protein> are functionally distinct receptors on <cell_type>T lymphocytes</cell_type> .


Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of intracellular signaling proteins , including Vav , Cbl , p85 phosphoinositide 3-kinase , and the Src family kinases Lck and Fyn .

Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of <protein>intracellular signaling proteins</protein> , including <protein>Vav</protein> , <protein>Cbl</protein> , <protein>p85 phosphoinositide 3-kinase</protein> , and the <protein>Src family kinases</protein> <protein>Lck</protein> and <protein>Fyn</protein> .


Ligation of CD3 also induces the tyrosine phosphorylation of HS1 , a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function .

Ligation of <protein>CD3</protein> also induces the tyrosine phosphorylation of <protein>HS1</protein> , a <protein>75-kDa hematopoietic cell-specific intracellular signaling protein</protein> of unknown function .


We have examined changes in HS1 phosphorylation after differential stimulation of CD3 , CD2 , and CD28 to elucidate its role in T cells and to further delineate the signaling pathways recruited by these receptors .

We have examined changes in <protein>HS1</protein> phosphorylation after differential stimulation of <protein>CD3</protein> , <protein>CD2</protein> , and <protein>CD28</protein> to elucidate its role in <cell_type>T cells</cell_type> and to further delineate the signaling pathways recruited by these receptors .


Unlike ligation of CD3 , stimulation with anti-CD28 mAb or CHO cells expressing the CD28 ligands CD80 or CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cells .

Unlike ligation of <protein>CD3</protein> , stimulation with <protein>anti-CD28 mAb</protein> or <cell_line>CHO cells</cell_line> expressing the <protein>CD28 ligands</protein> <protein>CD80</protein> or <protein>CD86</protein> did not lead to tyrosine phosphorylation of <protein>HS1</protein> in <cell_line>Jurkat T cells</cell_line> .


Additionally , no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT ( nuclear factor of activated T cells ) .

Additionally , no tyrosine phosphorylation of <protein>HS1</protein> was induced by <cell_type>mitogenic pairs</cell_type> of <protein>anti-CD2 mAbs</protein> capable of activating the <protein>transcription factor NFAT</protein> ( <protein>nuclear factor of activated T cells</protein> ) .


Costimulation through CD28 and/or CD2 did not modulate the CD3 -dependent phosphorylation of HS1 .

Costimulation through <protein>CD28</protein> and/or <protein>CD2</protein> did not modulate the <protein>CD3</protein> -dependent phosphorylation of <protein>HS1</protein> .


In vivo studies indicated that CD3 -induced HSI phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD45 , did not require MEK1 kinase activity , and was regulated by protein kinase C activation .

In vivo studies indicated that <protein>CD3</protein> -induced <protein>HSI</protein> phosphorylation was dependent upon both the <protein>Src family tyrosine kinase</protein> <protein>Lck</protein> and the <protein>tyrosine phosphatase</protein> <protein>CD45</protein> , did not require <protein>MEK1</protein> kinase activity , and was regulated by <protein>protein kinase C</protein> activation .


Thus , although CD3 , CD28 , and CD2 activate many of the same signaling molecules , they differed in their capacity to induce the tyrosine phosphorylation of HSI .

Thus , although <protein>CD3</protein> , <protein>CD28</protein> , and CD2 activate many of the same <protein>signaling molecules</protein> , they differed in their capacity to induce the tyrosine phosphorylation of <protein>HSI</protein> .


Furthermore , activation-dependent tyrosine phosphorylation of HS1 was not required for NFAT transcriptional activation .

Furthermore , activation-dependent tyrosine phosphorylation of <protein>HS1</protein> was not required for <protein>NFAT</protein> transcriptional activation .


c-fos and c-jun mRNA expression in activated cord and adult lymphocytes : an analysis by Northern hybridization .

c-fos and c-jun mRNA expression in <cell_type>activated cord and adult lymphocytes</cell_type> : an analysis by Northern hybridization .


BACKGROUND AND OBJECTIVES : To further analyze the neonatal immune response to an antigenic challenge such as blood transfusion , c-fos and c-jun mRNA expression were analyzed in twelve in-vitro-stimulated normal cord blood and ten in-vitro-stimulated normal adult peripheral blood lymphocyte samples .

BACKGROUND AND OBJECTIVES : To further analyze the neonatal immune response to an antigenic challenge such as blood transfusion , c-fos and c-jun mRNA expression were analyzed in twelve in-vitro-stimulated normal cord blood and ten <cell_type>in-vitro-stimulated normal adult peripheral blood lymphocyte samples</cell_type> .


MATERIALS AND METHODS : Lymphocyte samples were stimulated by either the mitogen phytohemagglutinin ( PHA ) or the monoclonal antibody alphaCD3 .

MATERIALS AND METHODS : <cell_type>Lymphocyte samples</cell_type> were stimulated by either the <protein>mitogen phytohemagglutinin</protein> ( <protein>PHA</protein> ) or the monoclonal antibody <protein>alphaCD3</protein> .


Proliferation rate and Northern blot hybridization were employed .


RESULTS : Cord lymphocytes revealed a greater proliferation rate with PHA and alphaCD3 than adult lymphocytes ( p = 0.0081 and 0.0023 , respectively ) .

RESULTS : Cord lymphocytes revealed a greater proliferation rate with <protein>PHA</protein> and <protein>alphaCD3</protein> than adult lymphocytes ( p = 0.0081 and 0.0023 , respectively ) .


In addition , Northern blot analysis of cord and adult samples revealed similar maximal increases in c-fos ( 99+/-15 and 126+/-11 % , p = 0.0126 ) and c-jun ( 123+/-9 and 185+/-38 % , p = 0.0291 ) mRNA expression , respectively , as early as 15 min post- alphaCD3 stimulation .

In addition , Northern blot analysis of cord and adult samples revealed similar maximal increases in <rna>c-fos</rna> ( 99+/-15 and 126+/-11 % , p = 0.0126 ) and <rna>c-jun ( 123+/-9 and 185+/-38 % , p = 0.0291 ) mRNA</rna> expression , respectively , as early as 15 min post- <protein>alphaCD3</protein> stimulation .


Adult lymphocytes showed an equivalent increase in mRNA expression of c-fos and c-jun ( 140+/-25 and 155+/-31 % ) at 30 min post- PHA stimulation , while cord lymphocyte maximum c-fos and c-jun expression ( 82+/-6 and 142+/-12 % ) occurred at 15 min post- PHA stimulation ( c-fos , p = 0.0354 ; c-jun , p = 0.0112 ) .

Adult lymphocytes showed an equivalent increase in mRNA expression of <dna>c-fos</dna> and <dna>c-jun</dna> ( 140+/-25 and 155+/-31 % ) at 30 min post- <protein>PHA</protein> stimulation , while <cell_type>cord lymphocyte</cell_type> maximum c-fos and c-jun expression ( 82+/-6 and 142+/-12 % ) occurred at 15 min post- <protein>PHA</protein> stimulation ( <dna>c-fos</dna> , p = 0.0354 ; <dna>c-jun</dna> , p = 0.0112 ) .


CONCLUSION : Although cord lymphocyte proliferation rates were significantly greater than those of adult lymphocytes following stimulation , lymphocyte activation , as analyzed by c-fos and c-jun mRNA expression , appears similar in both cord and adult samples .

CONCLUSION : Although <cell_type>cord lymphocyte</cell_type> proliferation rates were significantly greater than those of adult lymphocytes following stimulation , lymphocyte activation , as analyzed by c-fos and c-jun mRNA expression , appears similar in both cord and adult samples .


We conclude that cord lymphocyte activation exhibits an adult-type profile .


Fcgamma receptor -mediated mitogen-activated protein kinase activation in monocytes is independent of Ras .

<protein>Fcgamma receptor</protein> -mediated <protein>mitogen-activated protein kinase</protein> activation in <cell_type>monocytes</cell_type> is independent of <protein>Ras</protein> .


Receptors for the Fc portion of immunoglobulin molecules ( FcR ) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense , including phagocytosis , cell cytotoxicity , production and secretion of inflammatory mediators , and modulation of the immune response .

Receptors for the <protein>Fc portion</protein> of <protein>immunoglobulin molecules</protein> ( <protein>FcR</protein> ) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense , including phagocytosis , cell cytotoxicity , production and secretion of <protein>inflammatory mediators</protein> , and modulation of the immune response .


Cross-linking of FcR with immune complexes leads , first to activation of protein-tyrosine kinases .

Cross-linking of <protein>FcR</protein> with <protein>immune complexes</protein> leads , first to activation of <protein>protein-tyrosine kinases</protein> .


The molecular events that follow and that transduce signals from these receptors to the nucleus are still poorly defined .


We have investigated the signal transduction pathway from Fc receptors that leads to gene activation and production of cytokines in monocytes .

We have investigated the signal transduction pathway from <protein>Fc receptors</protein> that leads to gene activation and production of <protein>cytokines</protein> in <cell_type>monocytes</cell_type> .


Cross-linking of FcR , on the THP-1 monocytic cell line , by immune complexes resulted in both activation of the transcription factor NF-kappaB and interleukin 1 production .

Cross-linking of <protein>FcR</protein> , on the <cell_line>THP-1 monocytic cell line</cell_line> , by <protein>immune complexes</protein> resulted in both activation of the <protein>transcription factor</protein> <protein>NF-kappaB</protein> and <protein>interleukin 1</protein> production .


These responses were completely blocked by tyrosine kinase inhibitors .

These responses were completely blocked by <protein>tyrosine kinase</protein> inhibitors .


In contrast , expression of dominant negative mutants of Ras and Raf-1 , in these cells , did not have any effect on FcR -mediated nuclear factor activation , suggesting that the mitogen-activated protein kinase ( MAPK ) signaling pathway was not used by these receptors .

In contrast , expression of <protein>dominant negative mutants</protein> of <protein>Ras</protein> and <protein>Raf-1</protein> , in these cells , did not have any effect on <protein>FcR</protein> -mediated <protein>nuclear factor</protein> activation , suggesting that the <protein>mitogen-activated protein kinase</protein> ( <protein>MAPK</protein> ) signaling pathway was not used by these receptors .


However , MAPK activation was easily detected by in vitro kinase assays , after FcR cross-linking with immune complexes .

However , <protein>MAPK</protein> activation was easily detected by in vitro kinase assays , after <protein>FcR</protein> cross-linking with <protein>immune complexes</protein> .


Using the specific MAPK /extracellular signal-regulated kinase kinase ( MAPK kinase ) inhibitor PD98059 , we found that MAPK activation is necessary for FcR -dependent activation of the nuclear factor NF-kappaB .

Using the specific <protein>MAPK</protein> /extracellular signal-regulated kinase kinase ( MAPK kinase ) inhibitor PD98059 , we found that <protein>MAPK</protein> activation is necessary for <protein>FcR</protein> -dependent activation of the <protein>nuclear factor</protein> <protein>NF-kappaB</protein> .


These results strongly suggest that the signaling pathway from Fc receptors leading to expression of different genes important to leukocyte biology , initiates with tyrosine kinases and requires MAPK activation ; but in contrast to other tyrosine kinase receptors , FcR -mediated MAPK activation does not involve Ras and Raf .

These results strongly suggest that the signaling pathway from <protein>Fc receptors</protein> leading to expression of different genes important to leukocyte biology , initiates with <protein>tyrosine kinases</protein> and requires <protein>MAPK</protein> activation ; but in contrast to other <protein>tyrosine kinase receptors</protein> , <protein>FcR</protein> -mediated <protein>MAPK</protein> activation does not involve <protein>Ras</protein> and <protein>Raf</protein> .


BCL-6 mutations in normal germinal center B cells : evidence of somatic hypermutation acting outside Ig loci .

<protein>BCL-6</protein> mutations in <cell_type>normal germinal center B cells</cell_type> : evidence of somatic hypermutation acting outside <dna>Ig loci</dna> .


The molecular mechanism involved in the process of antigen-driven somatic hypermutation of Ig genes is unknown , but it is commonly believed that this mechanism is restricted to the Ig loci .

The molecular mechanism involved in the process of antigen-driven somatic hypermutation of <dna>Ig genes</dna> is unknown , but it is commonly believed that this mechanism is restricted to the <dna>Ig loci</dna> .


B cell lymphomas commonly display multiple somatic mutations clustering in the 5'-regulatory region of BCL-6 , a proto-oncogene encoding for a POZ/Zinc finger transcriptional repressor expressed in germinal center ( GC ) B cells and required for GC formation .

<cell_type>B cell lymphomas</cell_type> commonly display multiple somatic mutations clustering in the <dna>5'-regulatory region</dna> of <protein>BCL-6</protein> , a <dna>proto-oncogene</dna> encoding for a <protein>POZ/Zinc finger transcriptional repressor</protein> expressed in <cell_type>germinal center ( GC ) B cells</cell_type> and required for GC formation .


To determine whether BCL-6 mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism , we screened single human tonsillar GC B cells for mutations occurring in the BCL-6 5'-noncoding region and in the Ig variable heavy chain sequences .

To determine whether <protein>BCL-6</protein> mutations represent a tumor-associated phenomenon or reflect a physiologic mechanism , we screened single <cell_type>human tonsillar GC B cells</cell_type> for mutations occurring in the <dna>BCL-6 5'-noncoding region</dna> and in the <dna>Ig variable heavy chain sequences</dna> .


Thirty percent of GC B cells , but not naive B cells , displayed mutations in the 742 bp region analyzed within the first intron of BCL-6 ( overall frequency : 5 x 10 ( -4 ) /bp ) .

Thirty percent of <cell_type>GC B cells</cell_type> , but not <cell_type>naive B cells</cell_type> , displayed mutations in the <dna>742 bp region</dna> analyzed within the first intron of <protein>BCL-6</protein> ( overall frequency : 5 x 10 ( -4 ) /bp ) .


Accordingly , an expanded survey in lymphoid malignancies showed that BCL-6 mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying mutated Ig variable heavy chain sequences .

Accordingly , an expanded survey in lymphoid malignancies showed that <protein>BCL-6</protein> mutations are restricted to B cell tumors displaying GC or post-GC phenotype and carrying <dna>mutated Ig variable heavy chain sequences</dna> .


These results indicate that the somatic hypermutation mechanism active in GC B cells physiologically targets non-Ig sequences .

These results indicate that the somatic hypermutation mechanism active in <cell_type>GC B cells</cell_type> physiologically targets <dna>non-Ig sequences</dna> .


The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF .

The <protein>AD1</protein> and <protein>AD2</protein> transactivation domains of <protein>E2A</protein> are essential for the antiapoptotic activity of the <protein>chimeric oncoprotein</protein> <protein>E2A-HLF</protein> .


The chimeric oncoprotein E2A-HLF , generated by the t ( 17 ; 19 ) chromosomal translocation in pro-B-cell acute lymphoblastic leukemia , incorporates the transactivation domains of E2A and the basic leucine zipper ( bZIP ) DNA-binding and protein dimerization domain of HLF ( hepatic leukemic factor ) .

The <protein>chimeric oncoprotein</protein> <protein>E2A-HLF</protein> , generated by the <dna>t ( 17 ; 19 ) chromosomal translocation</dna> in pro-B-cell acute lymphoblastic leukemia , incorporates the <protein>transactivation domains</protein> of <protein>E2A</protein> and the <protein>basic leucine zipper ( bZIP ) DNA-binding and protein dimerization domain</protein> of <protein>HLF</protein> ( <protein>hepatic leukemic factor</protein> ) .


The ability of E2A-HLF to prolong the survival of interleukin-3 ( IL-3 ) -dependent murine pro-B cells after IL-3 withdrawal suggests that it disrupts signaling pathways normally responsible for cell suicide , allowing the cells to accumulate as transformed lymphoblasts .

The ability of <protein>E2A-HLF</protein> to prolong the survival of <cell_line>interleukin-3 ( IL-3 ) -dependent murine pro-B cells</cell_line> after <protein>IL-3</protein> withdrawal suggests that it disrupts signaling pathways normally responsible for cell suicide , allowing the cells to accumulate as <cell_type>transformed lymphoblasts</cell_type> .


To determine the structural motifs that contribute to this antiapoptotic effect , we constructed a panel of E2A-HLF mutants and programmed their expression in IL-3-dependent murine pro-B cells ( FL5.12 line ) , using a zinc-inducible vector .

To determine the structural motifs that contribute to this antiapoptotic effect , we constructed a panel of <protein>E2A-HLF mutants</protein> and programmed their expression in <cell_line>IL-3-dependent murine pro-B cells</cell_line> ( <cell_line>FL5.12 line</cell_line> ) , using a zinc-inducible vector .


Neither the E12 nor the E47 product of the E2A gene nor the wild-type HLF protein was able to protect the cells from apoptosis induced by IL-3 deprivation .

Neither the <protein>E12</protein> nor the <protein>E47</protein> product of the <dna>E2A gene</dna> nor the <protein>wild-type HLF protein</protein> was able to protect the cells from apoptosis induced by <protein>IL-3</protein> deprivation .


Surprisingly , different combinations of disabling mutations within the HLF bZIP domain had little effect on the antiapoptotic property of the chimeric protein , so long as the amino-terminal portion of E2A remained intact .

Surprisingly , different combinations of disabling mutations within the <protein>HLF bZIP domain</protein> had little effect on the antiapoptotic property of the <protein>chimeric protein</protein> , so long as the amino-terminal portion of <protein>E2A</protein> remained intact .


In the context of a bZIP domain defective in DNA binding , mutants retaining either of the two transactivation domains of E2A were able to extend cell survival after growth factor deprivation .

In the context of a <protein>bZIP domain</protein> defective in DNA binding , mutants retaining either of the two <protein>transactivation domains</protein> of <protein>E2A</protein> were able to extend cell survival after <protein>growth factor</protein> deprivation .


Thus , the block of apoptosis imposed by E2A-HLF in pro-B lymphocytes depends critically on the transactivating regions of E2A .

Thus , the block of apoptosis imposed by <protein>E2A-HLF</protein> in <cell_type>pro-B lymphocytes</cell_type> depends critically on the <protein>transactivating regions</protein> of <protein>E2A</protein> .


Since neither DNA binding nor protein dimerization through the bZIP domain of HLF is required for this effect , we propose mechanisms whereby protein-protein interactions with the amino-terminal region of E2A allow the chimera to act as a transcriptional cofactor to alter the expression of genes regulating the apoptotic machinery in pro-B cells .

Since neither DNA binding nor protein dimerization through the <protein>bZIP domain</protein> of <protein>HLF</protein> is required for this effect , we propose mechanisms whereby protein-protein interactions with the amino-terminal region of <protein>E2A</protein> allow the <protein>chimera</protein> to act as a transcriptional cofactor to alter the expression of genes regulating the apoptotic machinery in <cell_type>pro-B cells</cell_type> .


Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin .

Induction of <protein>Mn SOD</protein> in <cell_type>human monocytes</cell_type> without <protein>inflammatory cytokine</protein> production by a <protein>mutant endotoxin</protein> .


Endotoxin selectively induces monocyte Mn superoxide dismutase ( SOD ) without affecting levels of Cu , Zn SOD , catalase , or glutathione peroxidase .

<protein>Endotoxin</protein> selectively induces <protein>monocyte Mn superoxide dismutase</protein> ( <protein>SOD</protein> ) without affecting levels of Cu , <protein>Zn SOD</protein> , <protein>catalase</protein> , or <protein>glutathione peroxidase</protein> .


However , little is known about the structure-activity relationship and the mechanism by which endotoxin induces Mn SOD .

However , little is known about the structure-activity relationship and the mechanism by which endotoxin induces <protein>Mn SOD</protein> .


In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3 ' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E. coli endotoxin and markedly stimulated the activation of human monocyte nuclear factor-kappaB and the induction of Mn SOD mRNA and enzyme activity .

In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3 ' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E. coli endotoxin and markedly stimulated the activation of <protein>human monocyte nuclear factor-kappaB</protein> and the induction of <rna>Mn SOD mRNA</rna> and enzyme activity .


However , in contrast to the wild-type endotoxin , it failed to induce significant production of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by monocytes and did not induce the phosphorylation and nuclear translocation of mitogen-activated protein kinase .

However , in contrast to the wild-type endotoxin , it failed to induce significant production of <protein>tumor necrosis factor-alpha</protein> and <protein>macrophage inflammatory protein-1alpha</protein> by <cell_type>monocytes</cell_type> and did not induce the phosphorylation and nuclear translocation of <protein>mitogen-activated protein kinase</protein> .


These results suggest that 1 ) lipid A myristoyl fatty acid , although it is important for the induction of inflammatory cytokine production by human monocytes , is not necessary for the induction of Mn SOD , 2 ) endotoxin -mediated induction of Mn SOD and inflammatory cytokines are regulated , at least in part , through different signal transduction pathways , and 3 ) failure of the mutant endotoxin to induce tumor necrosis factor-alpha production is , at least in part , due to its inability to activate mitogen-activated protein kinase .

These results suggest that 1 ) lipid A myristoyl fatty acid , although it is important for the induction of <protein>inflammatory cytokine</protein> production by <cell_type>human monocytes</cell_type> , is not necessary for the induction of <protein>Mn SOD</protein> , 2 ) <protein>endotoxin</protein> -mediated induction of <protein>Mn SOD</protein> and inflammatory <protein>cytokines</protein> are regulated , at least in part , through different signal transduction pathways , and 3 ) failure of the <protein>mutant endotoxin</protein> to induce <protein>tumor necrosis factor-alpha</protein> production is , at least in part , due to its inability to activate <protein>mitogen-activated protein kinase</protein> .


Regulation of the vitellogenin gene B1 promoter after transfer into hepatocytes in primary cultures .

Regulation of the <dna>vitellogenin gene B1 promoter</dna> after transfer into <cell_type>hepatocytes</cell_type> in primary cultures .


The estrogen-dependent and tissue-specific regulation of the Xenopus laevis vitellogenin gene B1 promoter has been studied by lipid-mediated DNA transfer into Xenopus hepatocytes in primary culture .

The estrogen-dependent and tissue-specific regulation of the Xenopus laevis <dna>vitellogenin gene B1 promoter</dna> has been studied by lipid-mediated DNA transfer into <cell_type>Xenopus hepatocytes</cell_type> in primary culture .


Hepatocytes achieve an efficient hormonal control of this promoter through a functional interaction between the estrogen responsive elements and a promoter proximal region upstream of the TATA box , which is characterized by a high density of binding sites for the transcription factors CTF/NF-1 , C/EBP and HNF3 .

Hepatocytes achieve an efficient hormonal control of this promoter through a functional interaction between the <dna>estrogen responsive elements</dna> and a <dna>promoter proximal region</dna> upstream of the <dna>TATA box</dna> , which is characterized by a high density of binding sites for the <protein>transcription factors</protein> <protein>CTF/NF-1</protein> , <protein>C/EBP</protein> and <protein>HNF3</protein> .


DNA accessibility to restriction enzymes within the chromosomal copy of the vitellogenin gene B1 promoter shows that the estrogen responsive unit and the promoter proximal region are sensitive to digestion in uninduced and estrogen-induced hepatocytes but not in erythrocyte nuclei .

DNA accessibility to <protein>restriction enzymes</protein> within the chromosomal copy of the <dna>vitellogenin gene B1 promoter</dna> shows that the <dna>estrogen responsive unit</dna> and the <dna>promoter proximal region</dna> are sensitive to digestion in uninduced and <cell_type>estrogen-induced hepatocytes</cell_type> but not in erythrocyte nuclei .


Together , these findings support the notion that chromatin configuration as well as the interplay of promoter elements mediate proper hormone-dependent and tissue-specific expression of the B1 vitellogenin gene .

Together , these findings support the notion that <dna>chromatin</dna> configuration as well as the interplay of <dna>promoter elements</dna> mediate proper hormone-dependent and tissue-specific expression of the <dna>B1 vitellogenin gene</dna> .


Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells .

Characterization of <protein>cytokine</protein> differential induction of <protein>STAT complexes</protein> in <cell_type>primary human T and NK cells</cell_type> .


Cytokines , IL-2 , IL-4 , IL-6 , IL-7 , IL-12 , and IL-15 are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear .

<protein>Cytokines</protein> , <protein>IL-2</protein> , <protein>IL-4</protein> , <protein>IL-6</protein> , <protein>IL-7</protein> , <protein>IL-12</protein> , and <protein>IL-15</protein> are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear .


Recent studies reveal that a family of transcription factors , signal transducers and activators of transcription ( STATs ) directly mediate many cytokine signals .

Recent studies reveal that a family of <protein>transcription factors</protein> , <protein>signal transducers and activators of transcription</protein> ( <protein>STATs</protein> ) directly mediate many <protein>cytokine</protein> signals .


We analyzed the activation of STATs in primary human T and NK cells by a variety of specific cytokines .

We analyzed the activation of <protein>STATs</protein> in <cell_type>primary human T and NK cells</cell_type> by a variety of specific <protein>cytokines</protein> .


We demonstrate that IL-12 induces STAT4 only in freshly isolated primary NK cells , but not in primary T cells , consistent with the lack of the IL-12 receptor in resting T cells .

We demonstrate that <protein>IL-12</protein> induces <protein>STAT4</protein> only in freshly isolated <cell_type>primary NK cells</cell_type> , but not in <cell_type>primary T cells</cell_type> , consistent with the lack of the <protein>IL-12 receptor</protein> in <cell_type>resting T cells</cell_type> .