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14
P52564
O43318
0
phosphorylation
up-regulates activity
0.764
The activity of tak1 to phosphorylate mkk6, which activates the jnk-p38 kinase pathway, is directly regulated by k63-linked polyubiquitination
SIGNOR-109497
P18545
P11488
0
binding
down-regulates activity
0.764
In the dark, PDE6 activity is suppressed by its inhibitory γ-subunit (Pγ). Rhodopsin-catalyzed activation of the G protein, transducin, relieves this inhibition and enhances PDE6 catalysis.
SIGNOR-260008
Q03135
P12931
0
phosphorylation
down-regulates activity
0.764
Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn
SIGNOR-118007
O95786
Q8IUD6
0
ubiquitination
up-regulates activity
0.764
Our data suggest that Riplet/RNF135 is a novel factor of the RIG-I pathway that is involved in the evoking of human innate immunity against RNA virus infection, and activates RIG-I through ubiquitination of its C-terminal region.
SIGNOR-265569
P27037
P18075
0
binding
up-regulates
0.764
We show that bmp7 and activin bind to the same type ii receptors, actrii and iib, but recruit distinct type i receptors into heteromeric receptor complexes
SIGNOR-60237
P10636
Q00535
0
phosphorylation
down-regulates activity
0.763
We found that cdk5 phosphorylated tau(441) at Thr-181, Ser-199, Ser-202, Thr-205, Thr-212, Ser-214, Thr-217, Thr-231, Ser-235, Ser-396, and Ser-404, but not at Ser-262, Ser-400, Thr-403, Ser-409, Ser-413, or Ser-422. GSK-3beta phosphorylated all the cdk5-catalyzed sites above except Ser-235.
SIGNOR-249321
P98177
P31749
0
phosphorylation
down-regulates
0.763
Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression
SIGNOR-252486
P10275
P07900
0
binding
up-regulates activity
0.763
The unliganded AR resides predominately in the cytoplasm as a heteromeric complex with hsp90 and other chaperone proteins. These chaperone proteins maintain AR in a form that is receptive to ligand binding. Regulation of gene expression by androgen-activated AR occurs through receptor nuclear translocation, dimerization, and binding to androgen response elements (AREs) in the DNA of target genes.
SIGNOR-251536
P34925
P56704
0
binding
up-regulates
0.763
Here, we report that ryk directly binds wnt-1 and wnt-3a via its wif domain and is required for the tcf.
SIGNOR-129580
Q9HCM2
Q14563
0
binding
up-regulates activity
0.763
We provide evidence suggesting that, in endothelial cells and glioblastoma cells, plexin-A4 is a required component of both Sema3A and Sema3B receptor complexes and inhibition of its expression nullifies both Sema3A and Sema3B signaling. The specificity for Sema3A or Sema3B is determined by the presence of plexin-A1 in Sema3A receptors and plexin-A2 in Sema3B receptors, and silencing each abrogates signaling by the appropriate semaphorin. 
SIGNOR-261811
P49190
Q96A98
0
binding
up-regulates
0.763
Subsequent efforts led to the isolation and definition of the primary structure of a novel peptide, referred to as tip39, from bovine hypothalamus and the synthetic peptide was shown to efficiently activate human, rat, and zebrafish pth2 receptors
SIGNOR-115124
P01106
Q969H0
0
ubiquitination
down-regulates quantity
0.762
We now show that the F-box protein Fbw7 interacts with and thereby destabilizes c-Myc in a manner dependent on phosphorylation of MB1. Whereas wild-type Fbw7 promoted c-Myc turnover in cells, an Fbw7 mutant lacking the F-box domain delayed it.
SIGNOR-243545
Q01201
Q00653
0
binding
up-regulates activity
0.762
The map3k14-activated chuk/ikka homodimer phosphorylates nfkb2/p100 associated with relb, inducing its proteolytic processing to nfkb2/p52 and the formation of nf-kappa-b relb-p52 complexes. The nf-kappa-b heterodimeric relb-p52 complex is a transcriptional activator.
SIGNOR-182835
Q08050
P06493
0
phosphorylation
up-regulates
0.762
A conserved phosphorylation site within the forkhead domain of foxm1b is required for its activation by cyclin-cdk1further analysis reveals that the leu-641 residue within an lxl motif is required for the recruitment of the cyclin-cdk complex, and the thr-596 residue is a critical cdk1 phosphorylation site within the activation domain of foxm1b. Cdk-dependent phosphorylation stimulates the foxm1b transcriptional activity
SIGNOR-187880
P28482
Q13115
0
dephosphorylation
down-regulates activity
0.762
Dephosphorylation and Inactivation of ERKs|A single protein kinase, MEK, activates ERK2 by phosphorylating threonine 183 and tyrosine 185
SIGNOR-248718
Q12866
Q14393
0
binding
up-regulates
0.762
We also found that gas6 stimulated tyrosine phosphorylation of axl, sky, and mer receptors ectopically expressed in chinese hamster ovary cells. Taken together, these findings suggest that gas6 is a common ligand for axl, sky, and mer, all known members of an axl/sky receptor subfamily.
SIGNOR-44953
Q13163
Q9Y2U5
0
phosphorylation
up-regulates
0.762
Mekk2 and mekk3 are mapk kinase kinases that bind, phosphorylate and activate mek5.
SIGNOR-104634
P04049
P30086
0
binding
down-regulates
0.762
Suppression of raf-1 kinase activity and map kinase by rkip. Rkip binds to raf-1, mek and erk, but not to ras.
SIGNOR-70838
P29353
P43405
0
phosphorylation
up-regulates
0.762
The syk-family kinases (syk and zap-70) were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site on sch1 (iso2).
SIGNOR-59635
P54753
P98172
0
binding
up-regulates
0.762
The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion.
SIGNOR-52517
P34981
P20396
0
binding
up-regulates activity
0.762
When TRH reaches the pars distalis of the pituitary, it regulates cells that express TRH receptor-1 (TRH-R1), such as the thyrotrophs. These cell types are subject to a multifactorial regulation that determines the extent and specificity of their response to TRH.
SIGNOR-267200
O60609
Q5T4W7
0
binding
up-regulates
0.762
Here, we report the identification of artemin, a novel member of the gdnf family, and demonstrate that it is the ligand for the former orphan receptor gfralpha3-ret. Artemin can also activate the gfralpha1-ret complex.
SIGNOR-63009
P20336
Q9UQ26
0
relocalization
up-regulates activity
0.762
N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle
SIGNOR-264377
O95235
P53350
0
phosphorylation
up-regulates activity
0.761
MKlp2 treated with Plk1 did not form the regular microtubule bundles seen with MKlp2 only; many single microtubules were seen instead, and the bundles that were formed were loose parallel arrays rather than the dense bundles seen with untreated MKlp2.|We propose that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis.
SIGNOR-278201
Q03431
P12272
0
binding
up-regulates activity
0.761
Prostate-specific antigen was found to specifically cleave PTHrP 1-141 in a time- and dose-dependent manner.|The preferred PSA cleavage site of PTHrP 1-141 was determined to be at the carboxyl-terminus of phenylalanine 23, consistent with chymotryptic-like enzymatic activity of PSA. Cleavage of PTHrP by PSA completely abolished the ability of PTHrP to stimulate cAMP production.
SIGNOR-270549
P15502
Q9UBX5
0
binding
up-regulates activity
0.761
The binding of tropoelastin fragments to fibulin-5 was directly proportional to their propensity to coacervate. Furthermore, the addition of fibulin-5 to tropoelastin facilitated coacervation. Taken together, the present study shows that fibulin-5 enhances elastic fiber formation in part by improving the self-association properties of tropoelastin.
SIGNOR-252137
P06213
Q14449
0
binding
down-regulates activity
0.761
Growth factor receptor-bound protein 14 (Grb14) interacts with insulin receptor (IR) through the between PH and SH2 (BPS) domain. Grb14-IR complex formation is initiated by insulin stimulation, and the binding event results in the inhibition of insulin signalling.
SIGNOR-264873
P63000
P52735
0
guanine nucleotide exchange factor
up-regulates
0.761
Vav2 activates rac1 / vav2 is an exchange factor for rho family gtpases.
SIGNOR-81645
P35222
P12931
0
phosphorylation
down-regulates activity
0.761
beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation.
SIGNOR-106458
Q9BXW9
O94782
0
deubiquitination
down-regulates activity
0.761
The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells
SIGNOR-263273
Q16763
Q9UM11
0
binding
up-regulates activity
0.761
Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity
SIGNOR-265081
P00533
Q9ULV8
0
polyubiquitination
down-regulates quantity by destabilization
0.761
In summary, we have shown that CBLC and AIP4 can interact and that these two E3 ligases could contribute to down-regulate EGFR signaling by ubiquitination. 
SIGNOR-272605
Q07817
Q9BXH1
0
binding
down-regulates activity
0.761
Only bimbh3 and bbc3 had comparable strong affinities for all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1.Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis.
SIGNOR-133811
P42702
P15018
0
binding
up-regulates
0.76
Lif binds at low-affinity to lifr, the structure of which is closely related to that of gp130 (42). Lifr then becomes heterodimerized with gp130 to form the high-affinity and signaling-competent complex (43). Osm utilizes this type of heterodimer, i.e. the lifr/gp130 complex (43, 44).
SIGNOR-139102
Q9UJU2
Q9UBE8
0
phosphorylation
down-regulates
0.76
Regulation of lymphoid enhancer factor 1/t-cell factor by mitogen-activated protein kinase-related nemo-like kinase-dependent phosphorylation in wnt/beta-catenin signaling.Nlk phosphorylates lef-1/tcf on two serine/threonine residues located in its central region. Mutation of both residues to alanine enhanced lef-1 transcriptional activity and rendered it resistant to inhibition by nlk.
SIGNOR-97812
Q13480
P00533
0
phosphorylation
up-regulates
0.76
Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (egfr)the entire protein was phosphorylated by regfr at eight tyrosine residues (y285, y373, y406, y447, y472, y619, y657, and y689).
SIGNOR-236400
P04637
Q8IW41
0
phosphorylation
up-regulates
0.76
Furthermore, we show that prak activates p53 by direct phosphorylation. prak phosphorylates p53 at ser37
SIGNOR-152847
P29474
P07900
0
binding
up-regulates
0.76
The binding of hsp90 to enos enhances the activation of enos.
SIGNOR-57211
P31749
O60346
0
dephosphorylation
down-regulates
0.76
Here, we identify a protein_ phosphatase, ph domain leucine-rich repeat protein_ phosphatase_ (phlpp), that specifically_ dephosphorylates_ the hydrophobic motif of_ akt_ (ser473 in akt1), triggering_ apoptosis_ and suppressing_ tumor_ growth.
SIGNOR-252601
P18206
P12931
0
phosphorylation
down-regulates activity
0.76
The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by SRC kinases, affects cell spreadingWhen phosphorylated, the vinculin tail exhibited significantly less binding to the vinculin head domain than the unphosphorylated tail.
SIGNOR-247424
P00533
Q13191
0
polyubiquitination
down-regulates quantity by destabilization
0.76
Here we describe that overexpression of cbl-b, a homologue of the c-cbl protooncogene, inhibits EGFR-induced apoptosis in MDA-MB-468 breast cancer cells. Overexpression of cbl-b results in a shortened duration of EGFR activation upon EGF stimulation. This is demonstrated by decreased amounts of phosphorylated EGFR as well as by inhibition of multiple downstream signaling pathways. The inhibition of signaling by cbl-b results from increased ubiquitination and degradation of the activated EGFR. 
SIGNOR-272934
P55211
Q13489
0
binding
down-regulates
0.76
Xiap, birc2 and birc3 were shown to bind pro-casp9. Iaps may suppress casp9 by direct auto-activation of pro-caspase-11
SIGNOR-56481
P27361
Q16690
0
dephosphorylation
down-regulates
0.76
Extracellular regulated kinases (erk) 1 and erk2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase vhr. A novel role in down-regulating the erk pathway
SIGNOR-67358
P15311
P61586
0
phosphorylation
up-regulates activity
0.76
Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.
SIGNOR-268429
P35222
P33151
0
binding
up-regulates activity
0.76
At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin
SIGNOR-265867
Q9HBX9
P04090
0
binding
up-regulates
0.76
Lgr7 and lgr8, are capable of mediating the action of relaxin through an adenosine 3',5'-monophosphate (camp)-dependent pathway
SIGNOR-114549
O95999
Q9H257
0
binding
up-regulates quantity by stabilization
0.76
To identify upstream signaling partners of BCL10, we performed a mammalian two-hybrid analysis and identified CARD9 as a novel CARD-containing protein that interacts selectively with the CARD activation domain of BCL10. When expressed in cells, CARD9 binds to BCL10 and activates NF-kappaB.
SIGNOR-257602
P10275
P12931
0
phosphorylation
up-regulates activity
0.76
In addition to the ability of Src to promotes castration resistant progression and AR activation, Src is involved in regulating prostate cancer cell migration, invasion, and metastasis and affects bone remodeling.|These data suggest that downstream of cell surface receptors, Ack1 mediates AR tyrosine phosphorylation at Tyr 267 and Src mediates AR tyrosine phosphorylation at Tyr 534.
SIGNOR-278168
P46108
P00519
0
phosphorylation
down-regulates activity
0.76
Negative regulation of crk by abl is essential for the antitumorigenic effects of ephrinb2,similar pathways may operate for crkl
SIGNOR-175135
P04637
Q96S44
0
phosphorylation
up-regulates
0.76
The intrinsic transcriptional activity of p53 was up-regulated by a transient transfection of prpk to cos-7 cells. Prpk was shown to bind to p53 and to phosphorylate p53 at ser-15.
SIGNOR-157471
P29474
P0DP23
0
binding
up-regulates activity
0.76
Electrons flow from the C-terminal reductase domain of one NOS monomer to the N-terminal oxygenase domain of the other NOS monomer (Siddhanta et al., 1998). The primary mode of enzyme activation is the binding of calcium-bound calmodulin to the N-terminal CaM-binding domain. This facilitates a structure change and the flow of electrons from NADPH through the flavins to the oxygenase domain of the other eNOS monomer
SIGNOR-251615
P42229
P28482
0
phosphorylation
up-regulates
0.76
Gh treatment of chinese hamster ovary cells stably transfected with the gh receptor (choa cells) led to rapid and transient activation of both stat5a and erk1 and erk2. these observations show, for the first time, direct physical interaction between erk and stat5a and also clearly identify serine 780 as a target for erk.
SIGNOR-66239
Q01718
Q8TCY5
0
binding
up-regulates activity
0.76
We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling.We have previously identified MRAP as an accessory protein for MC2R, required for receptor trafficking to the cell surface and the formation of a functional MC2R. Here we have identified MRAP2 as a homologue of MRAP. Like MRAP, MRAP2 is able to support MC2R cell-surface expression, producing a functional ACTH-responsive receptor.
SIGNOR-252360
Q15418
P28482
0
phosphorylation
up-regulates activity
0.759
Several lines of evidence indicate that the mapkap-k1 isoforms are also activated by mapks in vivo via the ras-dependent protein kinase cascade that is triggered by growth factors or tumor-promoting phorbol esters, such as phorbol 12-myristate 13-acetate (pma). here we identify six sites in mapkap-k1a that become phosphorylated in transfected cos-1 cells. The inactive form of mapkap-k1a in unstimulated cells is partially phosphorylated at ser222 and ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of thr360, ser364, thr574, and ser381 and increases the phosphorylation of ser222 and ser733.
SIGNOR-219308
Q99717
Q04771
0
phosphorylation
up-regulates
0.759
Bmp7 stimulated phosphorylation of endogenous smad1 and 5, formation of complexes with smad4 and induced the promoter for the homeobox gene, tlx2
SIGNOR-60171
O43521
P45983
0
phosphorylation
down-regulates quantity by destabilization
0.759
Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination.
SIGNOR-250132
Q9NQS7
P06493
0
phosphorylation
up-regulates
0.759
Here, we report that cdk1 phosphorylates thr 59 and thr 388 on inner centromere protein (incenp), which regulates the localization and kinase activity of aurora-b from prophase to metaphase. The replacement of endogenous incenp with t388a resulted in the delay of progression from metaphase to anaphase.
SIGNOR-143387
P78352
Q8NFZ4
0
relocalization
up-regulates activity
0.759
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264193
O00401
P12931
0
phosphorylation
up-regulates activity
0.759
An Src family tyrosine kinase, v-Src, phosphorylates and activates N-WASP.
SIGNOR-279487
P40763
P48357
0
binding
up-regulates activity
0.759
LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2.
SIGNOR-263495
P41968
P01189
0
binding
up-regulates activity
0.759
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins
SIGNOR-268705
P01019
Q9BYF1
0
cleavage
up-regulates activity
0.759
The ACE2 hydrolytic activity is dependent on the C terminus sequence of the substrate, which is evident from the data with the angiotensin peptides. After 2 h, ACE2 hydrolyzes Ang I partially and Ang II completely, although there is no hydrolysis of angiotensin 1–9, angiotensin 1–7, and angiotensin 1–5, which possess the same N terminus.
SIGNOR-256315
P36402
P35222
0
binding
up-regulates
0.759
Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation (fig 2?2),), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1
SIGNOR-134282
P48382
P33076
0
binding
up-regulates activity
0.759
RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA.
SIGNOR-240980
P42338
P01112
0
binding
up-regulates activity
0.759
Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. it was also described that ras interacts with pi3k in a direct manner.
SIGNOR-175189
P78352
O95886
0
binding
up-regulates activity
0.758
SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.
SIGNOR-264211
O43561
P06239
0
phosphorylation
up-regulates
0.758
Evidence of lat as a dual substrate for lck and syk in t lymphocytes.Lat is a linker protein essential for activation of t lymphocytes. Its rapid tyrosine-phosphorylation upon t cell receptor (tcr) stimulation recruits downstream signaling molecules for membrane targeting and activation.
SIGNOR-149182
O75581
P41221
0
binding
up-regulates activity
0.758
Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.
SIGNOR-131841
P25054
P49841
0
phosphorylation
up-regulates
0.758
Gsk-3beta-dependent phosphorylation of apc.
SIGNOR-75366
P21802
P08620
0
binding
up-regulates
0.758
The nine known fgf ligands and the four signaling fgf receptors (and their alternatively spliced variants) are expressed in specific spatial and temporal patterns. The activity of this signaling pathway is regulated by ligand binding specificity, heparan sulfate proteoglycans, and the differential signaling capacity of individual fgf receptors.
SIGNOR-42377
P48551
P05000
0
binding
up-regulates
0.758
Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.
SIGNOR-105982
Q13114
Q96RJ3
0
binding
down-regulates quantity by destabilization
0.758
Activation of br3 induces recruitment and degradation of traf3.
SIGNOR-168199
P84022
P11802
0
phosphorylation
down-regulates activity
0.757
We have mapped CDK4 and CDK2 phosphorylation sites to Thr 8, Thr 178 and Ser 212 in Smad3. Mutation of the CDK phosphorylation sites increases Smad3 transcriptional activity
SIGNOR-232142
Q9Y4H2
P06213
0
phosphorylation
down-regulates activity
0.757
Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor.
SIGNOR-251319
O95166
Q14596
0
binding
up-regulates
0.757
We performed glutathione s-transferase (gst) pull-down assays using extracts from hek293 cells overexpressing an ha-tagged nbr1(d50r) mutant, which lacks the ability to bind p62 (lamark et al., 2003) (figures s1a and s1b, available online), and gst fusions of six human atg8 homologs: gabarap, gabarapl1, gabarapl2, lc3a, lc3b, and lc3c. Indeed, nbr1 interacted with all these members of the mammalian atg8 protein family
SIGNOR-184261
Q14790
P28482
0
phosphorylation
down-regulates
0.757
We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity
SIGNOR-203473
P46531
Q8NES3
0
binding
up-regulates
0.757
We demonstrate that egf 12, a portion of the ligand-binding site, is modified with o-fucose and that this site is evolutionarily conserved. We also show that endogenous fringe proteins in chinese hamster ovary cells (lunatic fringe and radical fringe) as well as exogenous manic fringe modify o-fucose on many but not all egf repeats of mouse notch1.
SIGNOR-96537
O76064
Q14676
0
relocalization
up-regulates
0.757
Rnf8 relocalizes to dna damage sites via a phospho-dependent interaction with mdc1
SIGNOR-179820
P21730
P01031
0
binding
up-regulates activity
0.757
The chemotactic receptor for human C5a anaphylatoxin|The human C5a receptor was cloned from U937 and HL-60 cells and identified by high affinity binding when expressed in COS-7 cells.
SIGNOR-263457
Q9BXW4
Q9Y4P1
0
cleavage
up-regulates activity
0.757
Human atg4 homologues cleave the carboxyl termini of the three human atg8 homologues, microtubule-associated protein light chain 3 (lc3), gabarap, and gate-16.
SIGNOR-125489
O15151
Q93009
0
deubiquitination
up-regulates
0.757
Subsequently, hausp was shown to deubiquitinate mdm2 and mdmx, thereby stabilizing these proteins.
SIGNOR-139453
Q9UM11
Q9UKT4
0
ubiquitination
down-regulates
0.756
Emi1 binds cdh1 and inhibits apc-cdh1 activity.
SIGNOR-113385
Q00987
Q13315
0
phosphorylation
down-regulates activity
0.756
Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation.
SIGNOR-94268
Q13416
P24941
0
phosphorylation
up-regulates
0.756
We also found that horc2p is phosphorylated in vitro by cyclin a/cdk2, specifically at residues thr116 and thr226. These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability.
SIGNOR-116364
Q9Y566
Q9P1A6
0
relocalization
up-regulates activity
0.756
SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).
SIGNOR-264589
O95486
Q9NR31
0
binding
up-regulates quantity
0.756
Biogenesis of COPII vesicles is initiated by the activation of the small guanosine triphosphate (GTP)-binding protein secretion-associated Ras-related protein 1 (Sar1) at specialized subdomains of the ER, called ER exit sites (ERES) or transitional ER (tER). Membrane-bound Sar1 then recruits the inner COPII coat subcomplex, the Sec23/24 heterodimer.
SIGNOR-265303
Q04721
Q96JK9
0
binding
up-regulates
0.756
We report here the cloning and characterization of two new genes, maml2 and maml3, that also function as transcriptional coactivators for notch receptors.
SIGNOR-94097
P15336
Q15759
0
phosphorylation
up-regulates
0.756
Our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf-beta signaling via tak1 and p38. The two pathways, smad and tak1, synergistically enhance the activity of atf-2 which acts as their common nuclear target
SIGNOR-65586
P04637
Q15831
0
phosphorylation
up-regulates
0.756
We show that lkb1 physically associates with p53 in the nucleus and directly or indirectly phosphorylates p53 ser15 (previously shown to be phosphorylated by amp-dependent kinase) and p53 ser392
SIGNOR-150830
Q92529-2
Q16620
0
phosphorylation
up-regulates activity
0.755
We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo.
SIGNOR-273917
P12830
P12931
0
phosphorylation
down-regulates quantity by destabilization
0.755
Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation
SIGNOR-274048
P78352
Q9NZ94
0
relocalization
up-regulates activity
0.755
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264189
P00451
P00734
0
cleavage
up-regulates activity
0.755
Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689.
SIGNOR-263640
Q92529
Q16620
0
binding
up-regulates
0.755
Our present study established that n-shc and sck are expressed in a region-specific manner in the brain and that n-shc is a higher affinity adapter molecule than sck for trka and trkb receptors
SIGNOR-55864
O14920
O43318
0
phosphorylation
up-regulates activity
0.755
Tak1 become activated and then phosphorylates and activates ikk2 which in turn now phosphorylates ikba, marking it for k48-ubiquitination and proteasomal degradation. tak1 kinase complex phosphorylates and activates ikk in a manner that depends on traf6 and ubc13-uev1a our studies suggests that tak1_ acts as an upstream activating kinase for ikkbeta.
SIGNOR-109490
Q92889
Q8IY92
0
binding
up-regulates
0.755
Slx4 is a tumor suppressor that stimulates the activity of the nuclease xpf-ercc1 in dna crosslink repair.
SIGNOR-204890
Q9UDY8
Q9Y4K3
0
ubiquitination
up-regulates
0.755
Traf6 associates with malt1 in response to t-cell activation and can function as an e3 ligase for malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of malt1. Multiple lysine residues in the c-terminus of malt1 serve as acceptor sites for the assembly of polyubiquitin chains. (articolo-abstract)
SIGNOR-158554
P61586
Q8N1W1
0
guanine nucleotide exchange factor
up-regulates activity
0.755
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260546
O75581
Q9H461
0
binding
up-regulates activity
0.755
Ligands such as Wnt1, Wnt3a, and Wnt8 couple the seven-transmembrane domain receptor Frizzled (Fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (LRP5/6) to activate Wnt–Beta-catenin signaling.
SIGNOR-169638
Q13094
P06241
0
phosphorylation
down-regulates
0.755
P59fyn_phosphorylated slp-76 at intermediate levels but, significantly, this phosphorylation failed to induce vav?SLP-76 complex formation
SIGNOR-46851