GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
O00418	P0DP24	2	binding	up-regulates	0.461	The calmodulin-binding region is located between amino acids 51 and 96	SIGNOR-266321
Q14344	O95835	1	phosphorylation	down-regulates activity	0.2	These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes	SIGNOR-278051
Q5TGU0	P12235	2	binding	up-regulates activity	0.277	Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.	SIGNOR-261825
Q96Q27	P27361	0	phosphorylation	up-regulates activity	0.265	Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. \|Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.	SIGNOR-272241
Q15831	O60285	1	phosphorylation	up-regulates	0.546	A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.	SIGNOR-122686
O15111	Q99558	2	phosphorylation	down-regulates quantity by destabilization	0.698	Upon activation by nik, ikkalfa phosphorylates nik, triggering its proteolysis.	SIGNOR-165622
P42224	P07949	0	phosphorylation	up-regulates activity	0.275	In detail, RET and PTC3 induced STAT1 overexpression and phosphorylation at Ser 727 and Tyr 701.	SIGNOR-279276
O14920	P12931	0	phosphorylation	up-regulates	0.362	These results indicate that c-src can associate with ikkbeta and phosphorylate its tyrosine residues after tnf-alfa or tpa stimulation.	SIGNOR-99318
Q13002	Q6TDP4	2	binding	down-regulates quantity by destabilization	0.496	Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation.	SIGNOR-271612
Q05655	O76090	1	phosphorylation	down-regulates activity	0.2	We have identified a PKC phosphorylation site (S358) located in the C terminal region of hBest1 critical for channel rundown. Phosphorylation of this site by PKC activators and PP2A inhibitors reduces channel rundown.	SIGNOR-260880
P20226	Q7Z6Z7	0	ubiquitination	down-regulates quantity	0.337	Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.\|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.	SIGNOR-278696
Q9H204	P06239	0	phosphorylation	up-regulates	0.439	Y64 of magicin is phosphorylated by lck creating a sh2-grb2 binding motif	SIGNOR-148704
Q15208	P38936	1	phosphorylation	down-regulates quantity by destabilization	0.2	More importantly, with the direct regulation of p21 stability by phosphorylation on Ser 146, we define here the first downstream signaling mechanisms by which NDR kinases can control G1/S progression.\|NDR kinases regulate p21 stability by phosphorylation of S146 on p21. \|	SIGNOR-272961
P04049	Q92934	1	phosphorylation	down-regulates	0.66	The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins	SIGNOR-155293
P38936	Q16539	0	phosphorylation	up-regulates quantity by stabilization	0.445	The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.\|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro.	SIGNOR-89436
P15923	Q9P286	0	phosphorylation	up-regulates activity	0.2	The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). \|In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation	SIGNOR-275653
O75581	Q9GZT5	2	binding	up-regulates	0.56	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-131622
P18031	P10912	1	dephosphorylation	down-regulates activity	0.501	PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates	SIGNOR-248420
P08588	Q9HD26	0	relocalization	down-regulates	0.342	Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell	SIGNOR-128791
P09429	P14651	2	binding	up-regulates activity	0.298	We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.	SIGNOR-219902
P27361	P23443	1	phosphorylation	up-regulates activity	0.607	Thr 421/Ser 424 have been reported to be targeted by ERK1, 2 (39), JNK or p38 MAPKs (36). Interestingly, with a comparable kinetics, FSH represses ERK1, 2 constitutive phosphorylation in Sertoli cells isolated from 19-d-old rats	SIGNOR-134662
Q14938	A6NFN3	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268913
Q05086	P55036	1	polyubiquitination	down-regulates quantity by destabilization	0.463	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). Two additional Lys residues (Lys-126 and -135) were ubiquitinated by E6AP.	SIGNOR-272746
O00311	O75475	1	phosphorylation	up-regulates	0.334	We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold.	SIGNOR-25763
P49841	Q92585	1	phosphorylation	down-regulates	0.2	We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1	SIGNOR-187896
P28482	Q8N122	1	phosphorylation	up-regulates activity	0.518	We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1.	SIGNOR-188916
Q9UNW8	P63092	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256802
P28482	Q13625	1	phosphorylation	up-regulates activity	0.263	Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro.\|Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes.	SIGNOR-264414
Q9NYY3	P04637	1	phosphorylation	up-regulates activity	0.592	Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop.	SIGNOR-278980
P06493	O00311	1	phosphorylation	up-regulates	0.535	Hucdc7 and ask proteins can also be phosphorylated by cdks in vitro. Among four possible cdk phosphorylation sites of hucdc7, replacement of thr-376, corresponding to the activating threonine of cdk, with alanine (t376a mutant) dramatically reduces kinase activity, indicative of kinase activation by phosphorylation of this residue.	SIGNOR-78311
P38435	P00734	1	carboxylation	up-regulates activity	0.669	We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)\|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood.	SIGNOR-263676
Q9UQM7	P17676	1	phosphorylation	up-regulates activity	0.326	These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. \| Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.	SIGNOR-250617
O14757	P38936	1	phosphorylation	down-regulates quantity by destabilization	0.531	Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis.	SIGNOR-279325
O60563	P53350	0	phosphorylation	down-regulates activity	0.379	Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II.	SIGNOR-276501
Q07325	P49682	2	binding	up-regulates activity	0.782	The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells.	SIGNOR-260970
Q9NQC7	P20749	1	deubiquitination	down-regulates	0.512	Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.	SIGNOR-146774
Q13464	P19634	1	phosphorylation	up-regulates activity	0.685	We then engineered the T653A NHE1 mutant (ROCKA mutant), which can not be phosphorylated by p160ROCK.\|p160ROCK has also been shown to activate NHE1 at threonine 653 , in close vicinity to the Akt phosphorylation site at serine 648.	SIGNOR-279566
P22681	Q15303	2	binding	up-regulates	0.572	Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow.	SIGNOR-147841
Q92753	O00327	1	transcriptional regulation	up-regulates quantity by expression	0.478	RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs	SIGNOR-266852
Q05397	P00533	0	phosphorylation	up-regulates	0.595	In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases.	SIGNOR-167646
Q13153	P51114	1	phosphorylation	up-regulates activity	0.271	Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.	SIGNOR-273713
Q96EB6	Q02577	1	deacetylation	up-regulates activity	0.383	SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter	SIGNOR-254830
P17693	P26715	2	binding	up-regulates	0.631	Current models of nk cell function have supposed that the cd94/nkg2a heterodimer is interacting with an epitope common to classical hla class i	SIGNOR-56714
Q05D32	Q8TDR2	1	dephosphorylation	up-regulates quantity by stabilization	0.282	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273775
P55316	P48729	0	phosphorylation	up-regulates	0.2	Cki phosphorylation of ser 19 of foxg1 promotes nuclear import	SIGNOR-154386
P04183	P06493	0	phosphorylation	down-regulates	0.507	Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase.	SIGNOR-95574
Q14669	Q8IYW5	1	ubiquitination	down-regulates activity	0.465	Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.	SIGNOR-266783
Q92997	Q969G9	2	binding	down-regulates	0.704	Naked (nkd)1 and nkd2 are mammalian homologs of drosophila naked cuticle, which negatively regulates canonical wnt signaling by binding dishevelled. various reports using cell culture assays indicate that nkd-mediated wnt antagonism involves dvl degradation	SIGNOR-167984
Q9BY41	P17612	0	phosphorylation	down-regulates	0.494	Negative regulation of histone deacetylase 8 activity by cyclic amp-dependent protein kinase athe pka phosphoacceptor site of hdac8 is ser(39)	SIGNOR-120643
P53355	Q13224	1	phosphorylation	up-regulates activity	0.497	DAPK1 Activation Enhances the NR1 and NR2B Channel Conductance.\|Thus, an activated DAPK1 enhances NR1 and NR2B receptor channel conductance by phosphorylating NR2B subunit at Ser 1303.	SIGNOR-278397
Q9ULT6	Q15262	0	dephosphorylation	up-regulates activity	0.354	We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.	SIGNOR-260110
Q14938	P41161	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268886
Q8NI17	Q6EBC2	2	binding	up-regulates	0.648	Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor.	SIGNOR-125313
P54764	P51692	1	phosphorylation	up-regulates activity	0.375	We have shown here that EphA4 can phosphorylate STAT5B, but it is not yet clear whether the nuclear translocation of phosphorylated STAT5B is enhanced by EphA4.	SIGNOR-278934
P17612	P04049	1	phosphorylation	down-regulates activity	0.5	Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259).	SIGNOR-250041
Q9Y297	P10071	1	ubiquitination	down-regulates quantity by destabilization	0.671	Third, we and others have recently shown that only phosphorylated Ci/Gli3 are able to directly bind Slimb/BetaTrCP, that Gli3 is polyubiquitinated in the cell, and that mutations of 4 lysine residues, the putative ubiquitination sites in the Gli3 C-terminal region, inhibit Gli3 processing These observations further support the notion that Ci/Gli3 processing is carried out by the proteasome because the deletion of the cleavage site is expected to often disrupt the protease-mediated site-specific cleavage.	SIGNOR-145116
Q9H3D4	P24941	0	phosphorylation	down-regulates	0.246	Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively	SIGNOR-180759
O15169	P25054	2	binding	up-regulates activity	0.944	Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level.	SIGNOR-60043
P29350	P43403	1	dephosphorylation	down-regulates	0.588	We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.	SIGNOR-70237
Q9BR76	P17252	0	phosphorylation	down-regulates	0.324	We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.	SIGNOR-138733
P18031	P18031	2	dephosphorylation	down-regulates activity	0.2	Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex\| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B\|These results suggest that PTP1B can dephosphorylate itself under in vitro conditions.	SIGNOR-248423
P49759	P00519	1	phosphorylation	down-regulates	0.259	Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3	SIGNOR-181031
Q9H1B7	P01210	1	transcriptional regulation	down-regulates quantity by repression	0.307	EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.	SIGNOR-267155
Q9Y2T1	P49841	2	binding	up-regulates activity	0.832	It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.	SIGNOR-79950
P17252	Q6ZVD8	0	dephosphorylation	down-regulates quantity	0.253	In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha	SIGNOR-237051
O14786	Q04741	0	transcriptional regulation	up-regulates quantity by expression	0.2	EMX1 activates the transcription of Nrp1 in vitro.	SIGNOR-261593
P33993	P60228	2	binding	up-regulates quantity by stabilization	0.335	Our data show that INT6 interacts with a C-terminal domain of MCM7. Collectively, our observations suggest that INT6 restrains the increased degradation of MCM7 occurring during DNA replication by protecting its polyubiquitylated derivatives from the proteasome activity.	SIGNOR-259154
P17600	O75914	0	phosphorylation	up-regulates activity	0.334	Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release	SIGNOR-250246
P12272	P24941	0	phosphorylation	down-regulates	0.372	Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization	SIGNOR-68548
Q86UR1	P17612	0	phosphorylation	down-regulates	0.324	We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I	SIGNOR-163663
P49321	Q9Y4K3	2	binding	down-regulates activity	0.2	SNASP inhibits TLR4-induced NF-κB activation through TRAF6.Reciprocal immunoprecipitation and Western blot analyses confirmed that endogenous sNASP binds to TRAF6 in human monocyte cell line THP-1 (Figure 1B).Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.	SIGNOR-273655
Q00534	P06400	1	phosphorylation	down-regulates	0.769	Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively.	SIGNOR-135189
P05412	P84022	2	binding	down-regulates activity	0.75	These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity.	SIGNOR-256284
Q92585	P35222	2	binding	up-regulates	0.275	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-157843
O00254	P30679	2	binding	up-regulates activity	0.414	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257360
P42229	Q9Y6K1	1	transcriptional regulation	up-regulates quantity	0.326	… these data suggest that STAT5A positively regulates levels of DNMT3A, resulting in inactivation of tumor suppressor genes by epigenetic mechanisms in AML cells	SIGNOR-255631
P08908	P63096	2	binding	up-regulates activity	0.494	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256693
Q9Y3E7	Q9UN37	0	cleavage	up-regulates activity	0.625	Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.	SIGNOR-260847
P49336	Q15797	1	phosphorylation	down-regulates	0.383	Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161626
Q92544	Q16665	0	transcriptional regulation	down-regulates quantity by repression	0.2	Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.	SIGNOR-266705
Q06330	Q86X95	2	binding	up-regulates	0.669	In the mechanism of cbf1-mediated repression, cbf1 binds to a unique corepressor cir. Targeting of cir to cbf1 is an important component of repression. Cir binds to histone deacetylase and to sap30 and serves as a linker between cbf1 and the histone deacetylase complex.	SIGNOR-62932
P46531	Q13950	2	binding	down-regulates	0.38	Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.	SIGNOR-167627
P63092	P30559	2	binding	up-regulates activity	0.43	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256793
P42345	P23443	2	phosphorylation	up-regulates activity	0.96	S6K1 is a positive regulator of protein synthesis, and its activity is induced by mTOR-mediated phosphorylation.	SIGNOR-101328
Q13158	Q9BV47	0	dephosphorylation	down-regulates activity	0.366	This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation	SIGNOR-204559
Q13480	P06213	0	phosphorylation	up-regulates activity	0.502	HGab-1 was phosphorylated by IR at eight tyrosine residues (Y242, Y285, Y373, Y447, Y472, Y619, Y657, and Y689). t Gab-1 is the major binding partner of PI-3 kinase in 3T3L1 cells when stimulated with insulin	SIGNOR-251310
P24941	Q8WXE1	1	phosphorylation	up-regulates	0.579	Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response	SIGNOR-156928
O43474	Q9Y4K3	0	ubiquitination	up-regulates quantity by stabilization	0.285	We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization.	SIGNOR-277464
P51812	P31749	0	phosphorylation	down-regulates activity	0.265	Akt interacts with and phosphorylates RSK2 at S19.	SIGNOR-277548
P61586	Q13393	2	binding	up-regulates	0.697	Our results demonstrate that direct stimulation of pld1 in vivo by rhoa	SIGNOR-84953
Q99607	O15550	0	transcriptional regulation	down-regulates quantity by repression	0.279	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260031
P49841	P41236	1	phosphorylation	up-regulates activity	0.412	Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).	SIGNOR-251257
P27361	Q01860	1	phosphorylation	down-regulates	0.343	Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.	SIGNOR-192101
Q9UJX6	O14640	2	binding	down-regulates	0.239	We now report that the anaphase-promoting complex (apc/c) recognizes a d-box motif of dvl and ubiquitylates dvl on a highly conserved lysine residue.We now report that expression of the apc/c subunit anapc2 activates the apc/c-dependent degradation of dvl by disrupting canonical wnt signaling.	SIGNOR-188393
P63096	Q99677	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257057
Q16539	Q9BUB5	1	phosphorylation	up-regulates	0.672	Mnk1, but not mnk2, also binds strongly to the stress-activated kinase, p38.	SIGNOR-48346
O00141	P17612	0	phosphorylation	up-regulates activity	0.297	In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk.	SIGNOR-275972
P43026	O00238	2	binding	up-regulates activity	0.774	In contrast to other members of the TGF-beta superfamily, GDF-5 shows a pronounced specificity in type I receptor interaction in cross-link experiments binding only to BMP receptor IB (BMPR-IB). In mice, deletion of either GDF-5 or BMPR-IB results in a similar phenotype, indicating that GDF-5 signaling is highly dependent on BMPR-IB.	SIGNOR-256483
O75962	Q05397	0	phosphorylation	up-regulates activity	0.509	A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity.	SIGNOR-249188
Q9Y2R2	P22681	1	dephosphorylation	down-regulates	0.387	The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.	SIGNOR-65405

O00418

P0DP24

2

binding

up-regulates

0.461

The calmodulin-binding region is located between amino acids 51 and 96

SIGNOR-266321

Q14344

O95835

1

phosphorylation

down-regulates activity

0.2

These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes

SIGNOR-278051

Q5TGU0

P12235

2

binding

up-regulates activity

0.277

Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.

SIGNOR-261825

Q96Q27

P27361

0

phosphorylation

up-regulates activity

0.265

Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.

SIGNOR-272241

Q15831

O60285

1

phosphorylation

up-regulates

0.546

A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.

SIGNOR-122686

O15111

Q99558

2

phosphorylation

down-regulates quantity by destabilization

0.698

Upon activation by nik, ikkalfa phosphorylates nik, triggering its proteolysis.

SIGNOR-165622

P42224

P07949

0

phosphorylation

up-regulates activity

0.275

In detail, RET and PTC3 induced STAT1 overexpression and phosphorylation at Ser 727 and Tyr 701.

SIGNOR-279276

O14920

P12931

0

phosphorylation

up-regulates

0.362

These results indicate that c-src can associate with ikkbeta and phosphorylate its tyrosine residues after tnf-alfa or tpa stimulation.

SIGNOR-99318

Q13002

Q6TDP4

2

binding

down-regulates quantity by destabilization

0.496

Here, we report that actinfilin is able to bind to GluR6, a kainate-type glutamate receptor subunit, and target GluR6 for degradation. Like many members of its protein family, actinfilin acts as a substrate adaptor, binding Cullin 3 (Cul3) and linking GluR6 to the E3 ubiquitin-ligase complex. Together our data demonstrate that actinfilin acts as a scaffold, linking GluR6 to the Cul3 ubiquitin ligase to provide a novel mechanism for kainate receptor degradation.

SIGNOR-271612

Q05655

O76090

1

phosphorylation

down-regulates activity

0.2

We have identified a PKC phosphorylation site (S358) located in the C terminal region of hBest1 critical for channel rundown. Phosphorylation of this site by PKC activators and PP2A inhibitors reduces channel rundown.

SIGNOR-260880

P20226

Q7Z6Z7

0

ubiquitination

down-regulates quantity

0.337

Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation.

SIGNOR-278696

Q9H204

P06239

0

phosphorylation

up-regulates

0.439

Y64 of magicin is phosphorylated by lck creating a sh2-grb2 binding motif

SIGNOR-148704

Q15208

P38936

1

phosphorylation

down-regulates quantity by destabilization

0.2

More importantly, with the direct regulation of p21 stability by phosphorylation on Ser 146, we define here the first downstream signaling mechanisms by which NDR kinases can control G1/S progression.|NDR kinases regulate p21 stability by phosphorylation of S146 on p21. |

SIGNOR-272961

P04049

Q92934

1

phosphorylation

down-regulates

0.66

The activation of several major anti-apoptotic signaling pathways correlates with an increase in the phosphorylation of bad on ser-112, ser-136, and ser-155. These phosphorylation events result in bad inactivation through sequestration by 14-3-3 proteins

SIGNOR-155293

P38936

Q16539

0

phosphorylation

up-regulates quantity by stabilization

0.445

The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro.

SIGNOR-89436

P15923

Q9P286

0

phosphorylation

up-regulates activity

0.2

The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation

SIGNOR-275653

O75581

Q9GZT5

2

binding

up-regulates

0.56

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-131622

P18031

P10912

1

dephosphorylation

down-regulates activity

0.501

PTPH1 only bound Tyr534, whereas PTP1B and TC-PTP bound multiple phosphopeptides. Earlier work suggests that Tyr332, Tyr487, Tyr534, Tyr566, and Tyr627 are all phosphorylated after GH stimulation (21). Apart from Tyr627, all of these also appear good PTP substrates

SIGNOR-248420

P08588

Q9HD26

0

relocalization

down-regulates

0.342

Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell

SIGNOR-128791

P09429

P14651

2

binding

up-regulates activity

0.298

We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein.

SIGNOR-219902

P27361

P23443

1

phosphorylation

up-regulates activity

0.607

Thr 421/Ser 424 have been reported to be targeted by ERK1, 2 (39), JNK or p38 MAPKs (36). Interestingly, with a comparable kinetics, FSH represses ERK1, 2 constitutive phosphorylation in Sertoli cells isolated from 19-d-old rats

SIGNOR-134662

Q14938

A6NFN3

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268913

Q05086

P55036

1

polyubiquitination

down-regulates quantity by destabilization

0.463

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s. Surprisingly, the same four Lys residues on S5a, Lys-74, Lys-122, Lys-262, and Lys-365 were ubiquitinated by MuRF1 and E6AP (Fig. 10). Two additional Lys residues (Lys-126 and -135) were ubiquitinated by E6AP.

SIGNOR-272746

O00311

O75475

1

phosphorylation

up-regulates

0.334

We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold.

SIGNOR-25763

P49841

Q92585

1

phosphorylation

down-regulates

0.2

We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1

SIGNOR-187896

P28482

Q8N122

1

phosphorylation

up-regulates activity

0.518

We found three proline-directed residues within raptor, ser(8), ser(696), and ser(863), which are directly phosphorylated by erk1/2. Expression of phosphorylation-deficient alleles of raptor revealed that phosphorylation of these sites by erk1/2 normally promotes mtorc1 activity and signaling to downstream substrates, such as 4e-bp1.

SIGNOR-188916

Q9UNW8

P63092

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256802

P28482

Q13625

1

phosphorylation

up-regulates activity

0.263

Hence ASPP2 can be phosphorylated at serine 827 by MAPK1 in vitro.|Phosphorylation of ASPP2 by MAPK is required for RAS-induced increased binding to p53 and increased transactivation of pro-apoptotic genes.

SIGNOR-264414

Q9NYY3

P04637

1

phosphorylation

up-regulates activity

0.592

Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop.

SIGNOR-278980

P06493

O00311

1

phosphorylation

up-regulates

0.535

Hucdc7 and ask proteins can also be phosphorylated by cdks in vitro. Among four possible cdk phosphorylation sites of hucdc7, replacement of thr-376, corresponding to the activating threonine of cdk, with alanine (t376a mutant) dramatically reduces kinase activity, indicative of kinase activation by phosphorylation of this residue.

SIGNOR-78311

P38435

P00734

1

carboxylation

up-regulates activity

0.669

We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood.

SIGNOR-263676

Q9UQM7

P17676

1

phosphorylation

up-regulates activity

0.326

These studies implicate Ser276 of CIEBPP as the major in vim phosphorylation site for CaMKII. | Phosphorylation of serine at position 276 within the leucine zipper of C/EBP beta appeared to confer calcium-regulated transcriptional stimulation of a promoter that contained binding sites for C/EBP beta.

SIGNOR-250617

O14757

P38936

1

phosphorylation

down-regulates quantity by destabilization

0.531

Responsible for this degradation is the checkpoint kinase Chk1, which phosphorylates p21(Waf1) on T145 and S146 residues and induces its proteasome-dependent proteolysis.

SIGNOR-279325

O60563

P53350

0

phosphorylation

down-regulates activity

0.379

Further analysis indicated that Plk1 could phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA polymerase II.

SIGNOR-276501

Q07325

P49682

2

binding

up-regulates activity

0.782

The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells.

SIGNOR-260970

Q9NQC7

P20749

1

deubiquitination

down-regulates

0.512

Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.

SIGNOR-146774

Q13464

P19634

1

phosphorylation

up-regulates activity

0.685

We then engineered the T653A NHE1 mutant (ROCKA mutant), which can not be phosphorylated by p160ROCK.|p160ROCK has also been shown to activate NHE1 at threonine 653 , in close vicinity to the Akt phosphorylation site at serine 648.

SIGNOR-279566

P22681

Q15303

2

binding

up-regulates

0.572

Erbb4 might not be able to directly recruit cbl, and therefore downregulation of this receptor is slow.

SIGNOR-147841

Q92753

O00327

1

transcriptional regulation

up-regulates quantity by expression

0.478

RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs

SIGNOR-266852

Q05397

P00533

0

phosphorylation

up-regulates

0.595

In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases.

SIGNOR-167646

Q13153

P51114

1

phosphorylation

up-regulates activity

0.271

Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.

SIGNOR-273713

Q96EB6

Q02577

1

deacetylation

up-regulates activity

0.383

SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter

SIGNOR-254830

P17693

P26715

2

binding

up-regulates

0.631

Current models of nk cell function have supposed that the cd94/nkg2a heterodimer is interacting with an epitope common to classical hla class i

SIGNOR-56714

Q05D32

Q8TDR2

1

dephosphorylation

up-regulates quantity by stabilization

0.282

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273775

P55316

P48729

0

phosphorylation

up-regulates

0.2

Cki phosphorylation of ser 19 of foxg1 promotes nuclear import

SIGNOR-154386

P04183

P06493

0

phosphorylation

down-regulates

0.507

Given that the dimeric form of tk1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract atp-dependent activation of tk1 by affecting its quaternary structure, thus attenuating its enzymatic function at the g2/m phase.

SIGNOR-95574

Q14669

Q8IYW5

1

ubiquitination

down-regulates activity

0.465

Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.

SIGNOR-266783

Q92997

Q969G9

2

binding

down-regulates

0.704

Naked (nkd)1 and nkd2 are mammalian homologs of drosophila naked cuticle, which negatively regulates canonical wnt signaling by binding dishevelled. various reports using cell culture assays indicate that nkd-mediated wnt antagonism involves dvl degradation

SIGNOR-167984

Q9BY41

P17612

0

phosphorylation

down-regulates

0.494

Negative regulation of histone deacetylase 8 activity by cyclic amp-dependent protein kinase athe pka phosphoacceptor site of hdac8 is ser(39)

SIGNOR-120643

P53355

Q13224

1

phosphorylation

up-regulates activity

0.497

DAPK1 Activation Enhances the NR1 and NR2B Channel Conductance.|Thus, an activated DAPK1 enhances NR1 and NR2B receptor channel conductance by phosphorylating NR2B subunit at Ser 1303.

SIGNOR-278397

Q9ULT6

Q15262

0

dephosphorylation

up-regulates activity

0.354

We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.

SIGNOR-260110

Q14938

P41161

1

transcriptional regulation

down-regulates quantity

0.2

By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development

SIGNOR-268886

Q8NI17

Q6EBC2

2

binding

up-regulates

0.648

Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor.

SIGNOR-125313

P54764

P51692

1

phosphorylation

up-regulates activity

0.375

We have shown here that EphA4 can phosphorylate STAT5B, but it is not yet clear whether the nuclear translocation of phosphorylated STAT5B is enhanced by EphA4.

SIGNOR-278934

P17612

P04049

1

phosphorylation

down-regulates activity

0.5

Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. Cyclic AMP (cAMP) blocks Raf-1 activation by stimulating its phosphorylation on serine 43 (Ser43), serine 233 (Ser233), and serine 259 (Ser259).

SIGNOR-250041

Q9Y297

P10071

1

ubiquitination

down-regulates quantity by destabilization

0.671

Third, we and others have recently shown that only phosphorylated Ci/Gli3 are able to directly bind Slimb/BetaTrCP, that Gli3 is polyubiquitinated in the cell, and that mutations of 4 lysine residues, the putative ubiquitination sites in the Gli3 C-terminal region, inhibit Gli3 processing These observations further support the notion that Ci/Gli3 processing is carried out by the proteasome because the deletion of the cleavage site is expected to often disrupt the protease-mediated site-specific cleavage.

SIGNOR-145116

Q9H3D4

P24941

0

phosphorylation

down-regulates

0.246

Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively

SIGNOR-180759

O15169

P25054

2

binding

up-regulates activity

0.944

Axin, an inhibitor of the wnt pathway, interacts with beta-catenin, gsk-3beta and apc and reduces the beta-catenin level.

SIGNOR-60043

P29350

P43403

1

dephosphorylation

down-regulates

0.588

We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.

SIGNOR-70237

Q9BR76

P17252

0

phosphorylation

down-regulates

0.324

We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.

SIGNOR-138733

P18031

2

dephosphorylation

down-regulates activity

0.2

Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B|These results suggest that PTP1B can dephosphorylate itself under in vitro conditions.

SIGNOR-248423

P49759

P00519

1

phosphorylation

down-regulates

0.259

Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3

SIGNOR-181031

Q9H1B7

P01210

1

transcriptional regulation

down-regulates quantity by repression

0.307

EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity.These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.

SIGNOR-267155

Q9Y2T1

P49841

2

binding

up-regulates activity

0.832

It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains.

SIGNOR-79950

P17252

Q6ZVD8

0

dephosphorylation

down-regulates quantity

0.253

In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha

SIGNOR-237051

O14786

Q04741

0

transcriptional regulation

up-regulates quantity by expression

0.2

EMX1 activates the transcription of Nrp1 in vitro.

SIGNOR-261593

P33993

P60228

2

binding

up-regulates quantity by stabilization

0.335

Our data show that INT6 interacts with a C-terminal domain of MCM7. Collectively, our observations suggest that INT6 restrains the increased degradation of MCM7 occurring during DNA replication by protecting its polyubiquitylated derivatives from the proteasome activity.

SIGNOR-259154

P17600

O75914

0

phosphorylation

up-regulates activity

0.334

Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release

SIGNOR-250246

P12272

P24941

0

phosphorylation

down-regulates

0.372

Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization

SIGNOR-68548

Q86UR1

P17612

0

phosphorylation

down-regulates

0.324

We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I

SIGNOR-163663

P49321

Q9Y4K3

2

binding

down-regulates activity

0.2

SNASP inhibits TLR4-induced NF-κB activation through TRAF6.Reciprocal immunoprecipitation and Western blot analyses confirmed that endogenous sNASP binds to TRAF6 in human monocyte cell line THP-1 (Figure 1B).Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways.

SIGNOR-273655

Q00534

P06400

1

phosphorylation

down-regulates

0.769

Phosphorylated by cdk6 and cdk4, and subsequently by cdk2 at ser-567 in g1, thereby releasing e2f1 which is then able to activate cell growth. Here we show that although these cdks phosphorylate multiple residues in prb, they do so with different residue selectivities in vitro;thr821 and thr826 are preferentially phosphorylated by cdk6 and cdk4, respectively.

SIGNOR-135189

P05412

P84022

2

binding

down-regulates activity

0.75

These results indicate that interaction between Smad3 and c-Jun may repress Smad3 transcriptional activity.

SIGNOR-256284

Q92585

P35222

2

binding

up-regulates

0.275

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-157843

O00254

P30679

2

binding

up-regulates activity

0.414

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257360

P42229

Q9Y6K1

1

transcriptional regulation

up-regulates quantity

0.326

… these data suggest that STAT5A positively regulates levels of DNMT3A, resulting in inactivation of tumor suppressor genes by epigenetic mechanisms in AML cells

SIGNOR-255631

P08908

P63096

2

binding

up-regulates activity

0.494

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256693

Q9Y3E7

Q9UN37

0

cleavage

up-regulates activity

0.625

Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.

SIGNOR-260847

P49336

Q15797

1

phosphorylation

down-regulates

0.383

Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161626

Q92544

Q16665

0

transcriptional regulation

down-regulates quantity by repression

0.2

Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.

SIGNOR-266705

Q06330

Q86X95

2

binding

up-regulates

0.669

In the mechanism of cbf1-mediated repression, cbf1 binds to a unique corepressor cir. Targeting of cir to cbf1 is an important component of repression. Cir binds to histone deacetylase and to sap30 and serves as a linker between cbf1 and the histone deacetylase complex.

SIGNOR-62932

P46531

Q13950

2

binding

down-regulates

0.38

Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.

SIGNOR-167627

P63092

P30559

2

binding

up-regulates activity

0.43

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256793

P42345

P23443

2

phosphorylation

up-regulates activity

0.96

S6K1 is a positive regulator of protein synthesis, and its activity is induced by mTOR-mediated phosphorylation.

SIGNOR-101328

Q13158

Q9BV47

0

dephosphorylation

down-regulates activity

0.366

This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation

SIGNOR-204559

Q13480

P06213

0

phosphorylation

up-regulates activity

0.502

HGab-1 was phosphorylated by IR at eight tyrosine residues (Y242, Y285, Y373, Y447, Y472, Y619, Y657, and Y689). t Gab-1 is the major binding partner of PI-3 kinase in 3T3L1 cells when stimulated with insulin

SIGNOR-251310

P24941

Q8WXE1

1

phosphorylation

up-regulates

0.579

Atrip is a cdk2 substrate, and cdk2-dependent phosphorylation of s224 regulates the ability of atr-atrip to promote cell cycle arrest in response to dna damage./ One possibility is s224 phosphorylation creates a binding site for another protein involved in the g2-m checkpoint response

SIGNOR-156928

O43474

Q9Y4K3

0

ubiquitination

up-regulates quantity by stabilization

0.285

We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization.

SIGNOR-277464

P51812

P31749

0

phosphorylation

down-regulates activity

0.265

Akt interacts with and phosphorylates RSK2 at S19.

SIGNOR-277548

P61586

Q13393

2

binding

up-regulates

0.697

Our results demonstrate that direct stimulation of pld1 in vivo by rhoa

SIGNOR-84953

Q99607

O15550

0

transcriptional regulation

down-regulates quantity by repression

0.279

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260031

P49841

P41236

1

phosphorylation

up-regulates activity

0.412

Protein phosphatase 1 (PP1) is complexed with inhibitor 2 (I-2) in the cytosol. In rabbit muscle extract PP1.I-2 is activated upon preincubation with ATP/Mg. This activation is caused by phosphorylation of I-2 on Thr(72) by glycogen synthase kinase 3 (GSK3).

SIGNOR-251257

P27361

Q01860

1

phosphorylation

down-regulates

0.343

Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.

SIGNOR-192101

Q9UJX6

O14640

2

binding

down-regulates

0.239

We now report that the anaphase-promoting complex (apc/c) recognizes a d-box motif of dvl and ubiquitylates dvl on a highly conserved lysine residue.We now report that expression of the apc/c subunit anapc2 activates the apc/c-dependent degradation of dvl by disrupting canonical wnt signaling.

SIGNOR-188393

P63096

Q99677

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257057

Q16539

Q9BUB5

1

phosphorylation

up-regulates

0.672

Mnk1, but not mnk2, also binds strongly to the stress-activated kinase, p38.

SIGNOR-48346

O00141

P17612

0

phosphorylation

up-regulates activity

0.297

In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk.

SIGNOR-275972

P43026

O00238

2

binding

up-regulates activity

0.774

In contrast to other members of the TGF-beta superfamily, GDF-5 shows a pronounced specificity in type I receptor interaction in cross-link experiments binding only to BMP receptor IB (BMPR-IB). In mice, deletion of either GDF-5 or BMPR-IB results in a similar phenotype, indicating that GDF-5 signaling is highly dependent on BMPR-IB.

SIGNOR-256483

O75962

Q05397

0

phosphorylation

up-regulates activity

0.509

A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity.

SIGNOR-249188

Q9Y2R2

P22681

1

dephosphorylation

down-regulates

0.387

The tyrosine phosphatase lyp1 was found to be constitutively associated with the proto-oncogene c-cbl in thymocytes and t cells. Overexpression of lyp1 reduces cbl tyrosine phosphorylation. It is known that cbl is heavily tyrosine phosphorylated after tcr stimulation and can associate with the syk and zap tyrosine kinases, negatively regulating their activities. Tyrosine phosphatases keep cbl in a basally dephosphorylated state.

SIGNOR-65405