GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
P01137	P02452	1	transcriptional regulation	up-regulates quantity by expression	0.485	COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity	SIGNOR-277678
Q5S007	P62841	1	phosphorylation	up-regulates activity	0.485	Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity.	SIGNOR-279058
P00540	Q02750	1	phosphorylation	up-regulates activity	0.485	Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.	SIGNOR-260920
Q13882	Q96P48	1	phosphorylation	up-regulates activity	0.485	ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.	SIGNOR-263188
P32238	P30679	1	binding	up-regulates activity	0.485	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-257410
P17612	Q12972	1	phosphorylation	down-regulates activity	0.484	NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A	SIGNOR-250033
Q05513	P08047	1	phosphorylation	up-regulates	0.484	Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.	SIGNOR-160774
Q14164	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.484	The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.	SIGNOR-167524
Q9H4A3	O95747	1	phosphorylation	up-regulates	0.484	Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)	SIGNOR-151659
P51149	Q8NEB9	1	guanine nucleotide exchange factor	up-regulates activity	0.484	The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7	SIGNOR-261302
Q9UEW8	P55017	1	phosphorylation	down-regulates activity	0.484	SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation\|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface\| the kinase (SPAK) that phosphorylates NCC at T53	SIGNOR-264623
Q9HBW0	O95837	1	binding	up-regulates activity	0.484	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-257431
P03951	P00740	1	cleavage	up-regulates activity	0.484	Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.\|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets.	SIGNOR-263537
Q13153	O14950	1	phosphorylation	up-regulates activity	0.484	It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].	SIGNOR-280053
P63151	P31749	1	binding	down-regulates activity	0.484	Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.\|Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural \|Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells.subunit (A), catalytic subunit (C), and a variable regulatory subunit (B).	SIGNOR-252637
P61073	P04899	1	binding	up-regulates activity	0.484	Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner	SIGNOR-278103
P06493	Q16659	1	phosphorylation	up-regulates	0.484	Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.	SIGNOR-164499
Q9UI47	P14923	1	relocalization	up-regulates quantity	0.484	Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14	SIGNOR-265494
Q9Y4I1	P63027	1	binding	up-regulates activity	0.484	Another potential role of myosin Va in LDCV exocytosis lies in facilitating the formation of the SNARE complex, which is needed for fusion of the vesicle with the plasma membrane. Notably, myosin Va binds to at least two SNARE proteins in a Ca2+-dependent manner: at micromolar Ca2+-levels, it binds to VAMP2 located in the membrane of the cargo vesicle via its globular tail domain	SIGNOR-269281
P49841	P53805	1	phosphorylation	up-regulates activity	0.484	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249359
P17481	P40426	1	binding	up-regulates activity	0.484	the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.	SIGNOR-223149
Q92765	Q9H1J5	1	binding	down-regulates	0.484	We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,	SIGNOR-51798
Q9P2K8	Q9BY44	1	phosphorylation	down-regulates activity	0.484	Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).	SIGNOR-280005
Q6Q0C0	Q99759	1	binding	up-regulates	0.484	Traf7 specifically interacts with and activates mekk3.	SIGNOR-123221
P30679	Q9NQ66	1	binding	up-regulates activity	0.484	This suggests that both Gal4 and Gal6 can activate PLC b1.	SIGNOR-278120
Q9UKC9	P30281	1	binding	down-regulates quantity by destabilization	0.484	Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation.	SIGNOR-271887
O43683	P04637	1	phosphorylation	up-regulates activity	0.484	In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].\|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].	SIGNOR-280199
P34925	O14640	1	binding	up-regulates	0.483	Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled.	SIGNOR-129568
O60285	P55212	1	phosphorylation	down-regulates activity	0.483	ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.	SIGNOR-250209
Q86Y13	P54253	1	polyubiquitination	down-regulates quantity by destabilization	0.483	HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation.	SIGNOR-272078
Q9UBY5	P50148	1	binding	up-regulates activity	0.483	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-257297
P14416	P63096	1	binding	up-regulates activity	0.483	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-256701
P49336	Q01094	1	phosphorylation	down-regulates	0.483	E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.	SIGNOR-181078
Q9HCM9	Q96BY2	1	binding	up-regulates quantity by stabilization	0.483	TRIM39 stabilizes MOAP-1 by inhibiting the poly-ubiquitination process of MOAP-1.In this study, we report the identification and characterization of TRIM39 as a binding partner of MOAP-1. TRIM39 is the first regulator of MOAP-1 protein stability identified.	SIGNOR-272911
Q7Z6J4	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.483	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-260552
P62873	Q9NQ66	1	binding	down-regulates	0.483	These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.	SIGNOR-44369
P16284	P28907	1	binding	up-regulates activity	0.483	As a receptor, CD38 interacts with its ligand CD31 [15,16]. CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a 130 kDa type I transmembrane glycoprotein that consists of six extracellular immunoglobulin-like homology domains, a 19-residue transmembrane domain, and a 118-residue cytoplasmic tail	SIGNOR-264254
Q8TDC3	P30307	1	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
Q9UKC9	Q96GD4	1	binding	down-regulates quantity by destabilization	0.483	The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.	SIGNOR-272097
Q9UGL1	P55771	1	binding	up-regulates activity	0.483	Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression	SIGNOR-223875
P27361	Q92934	1	phosphorylation	down-regulates	0.483	Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.	SIGNOR-188172
O43791	Q9UER7	1	ubiquitination	down-regulates quantity	0.483	These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.	SIGNOR-268858
P31749	Q13363	1	phosphorylation	down-regulates quantity	0.483	Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.\|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.	SIGNOR-278304
P67775	Q04206	1	dephosphorylation	down-regulates	0.483	Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.	SIGNOR-110959
P01106	Q13616	1	transcriptional regulation	up-regulates quantity by expression	0.483	Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2	SIGNOR-102749
Q9NYY3	Q969H0	1	phosphorylation	down-regulates	0.483	Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176	SIGNOR-196448
O43303	Q12798	1	binding	up-regulates activity	0.483	We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.	SIGNOR-265966
Q86UF1	O14672	1	binding	up-regulates activity	0.483	Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.	SIGNOR-261251
Q96EP1	Q14527	1	polyubiquitination	down-regulates quantity by destabilization	0.482	CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.	SIGNOR-271460
P12757	Q15797	1	binding	down-regulates	0.482	Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7	SIGNOR-195636
P61244	Q14582	1	binding	up-regulates activity	0.482	the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.	SIGNOR-240224
P06493	Q8TD19	1	phosphorylation	up-regulates activity	0.482	We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.	SIGNOR-273889
Q16644	Q6JBY9	1	phosphorylation	down-regulates activity	0.482	Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.	SIGNOR-263082
P35637	Q08211	1	relocalization	down-regulates activity	0.482	We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.\|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. \| We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons	SIGNOR-262810
P06748	Q969H0	1	binding	up-regulates quantity	0.482	We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7 , a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabili- zation of Fbw7	SIGNOR-245084
Q14258	Q13887	1	polyubiquitination	down-regulates quantity by destabilization	0.482	The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.	SIGNOR-271908
Q13315	O95863	1	phosphorylation	up-regulates activity	0.482	ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.	SIGNOR-279587
P21918	P63092	1	binding	up-regulates activity	0.482	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-256771
P45984	P40763	1	phosphorylation	up-regulates	0.482	Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.	SIGNOR-179275
P27361	P07101	1	phosphorylation	up-regulates	0.482	In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11	SIGNOR-34678
Q9P2G9	Q13702	1	binding	down-regulates quantity by destabilization	0.482	We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn.	SIGNOR-271781
P53350	P11388	1	phosphorylation	up-regulates	0.481	Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin	SIGNOR-182844
P17252	Q01970	1	phosphorylation	down-regulates	0.481	These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.	SIGNOR-58859
P23470	P00533	1	dephosphorylation	down-regulates activity	0.481	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254699
P49841	Q04721	1	phosphorylation	down-regulates activity	0.481	We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.	SIGNOR-101570
P35548	Q96T58	1	binding	up-regulates	0.481	Furthermore, in addition to msx2, both tlx1 and nkx2-5 proteins interacted with notch-pathway repressors, spen/mint/sharp and tle1/grg1, representing a potential mechanism for (de)regulation.	SIGNOR-188572
Q96SB3	Q96N96	1	binding	up-regulates activity	0.481	Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). Neurabin2 is required for Asef2-induced filopodia formation. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation.	SIGNOR-269174
Q00535	P04150	1	phosphorylation	down-regulates activity	0.481	Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.\| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue	SIGNOR-154405
Q00341	P49711	1	binding	up-regulates activity	0.481	Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19. vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of β-globin, and several regions within the Igf2/H19 locus. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.	SIGNOR-266693
Q92793	P10243	1	binding	up-regulates activity	0.481	CBP co-operates functionally with A-Myb	SIGNOR-240984
Q15831	Q9H0K1	1	phosphorylation	up-regulates	0.481	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-122788
P62714	P31751	1	dephosphorylation	down-regulates	0.481	These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity	SIGNOR-42123
Q03060	P60568	1	transcriptional regulation	down-regulates quantity by repression	0.481	In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.	SIGNOR-261576
P11309	P38936	1	phosphorylation	up-regulates quantity by stabilization	0.481	Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo	SIGNOR-164642
P09958	P04275	1	cleavage	up-regulates activity	0.481	Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine	SIGNOR-260368
P43220	P63092	1	binding	up-regulates activity	0.481	The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3)	SIGNOR-278137
Q16659	Q9Y6Q9	1	phosphorylation	up-regulates	0.481	Here, we report that erk3 interacted with and phosphorylated steroid receptor coactivator 3 (src-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (s857)	SIGNOR-196957
Q01726	P63092	1	binding	up-regulates activity	0.481	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-268697
P68036	Q6ZMZ0	1	binding	up-regulates activity	0.481	We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and	SIGNOR-271591
P18825	P63096	1	binding	up-regulates activity	0.48	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-256699
Q99835	Q9NRP7	1	binding	up-regulates	0.48	Smo then activates stk36 serine/threonine kinase to stabilize gli family members and to phosphorylate sufu for nuclear accumulation of gli.\| sufu binds to the kinesin cos2 to transduce the hh signal downstream of smo	SIGNOR-150540
Q9UMS4	P15927	1	polyubiquitination	up-regulates activity	0.48	PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.	SIGNOR-272075
P42338	P49841	1	phosphorylation	down-regulates activity	0.48	In our cultures, both p110alpha and p110beta phosphorylated GSK-3beta at Ser9 confirming previous data.\|Whereas p110alpha reduced the protein levels of the CDK2-inhibitor p27 Kip1, p110beta phosphorylated and inactivated GSK-3beta.	SIGNOR-279089
P42229	Q9BZS1	1	null	up-regulates	0.48	We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cell	SIGNOR-254301
Q12841	Q14689	1	binding	up-regulates activity	0.48	We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. The work in the current study identifies DIP2A as a novel receptor for FSTL1 that mediates Akt activation and cell survival and function in cardiovascular cells in vitro.	SIGNOR-266603
P28482	Q8IW41	1	phosphorylation	up-regulates	0.48	Activated following phosphorylation at thr-182 by p38-alpha/mapk14, p38-beta/mapk11, erk2/mapk1, erk3/mapk6, and erk4/mapk4.	SIGNOR-58127
Q5S007	Q92997	1	binding	up-regulates	0.48	Subsequent assays confirmed a direct interaction between the lrrk2 roccor domain and all three human dvl proteins, these data are consistent with a role for lrrk2 in the activation of canonical wnt signaling bringing dvl proteins to cellular membranes.	SIGNOR-202187
Q13131	P04637	1	phosphorylation	up-regulates	0.48	Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest	SIGNOR-135960
P12931	O60500	1	phosphorylation	up-regulates activity	0.48	Inhibition of Src kinase dependent Nephrin phosphorylation achieved by incubation of WT-Nephrin-overexpressing cells with 1 mum PP2 abolished the positive effect of Nephrin on GSIR (XREF_FIG D).\|We were able to demonstrate a complete prevention of Nephrin phosphorylation, confirming that Nephrin phosphorylation is mediated by Src.	SIGNOR-280129
Q8IY84	P30291	1	phosphorylation	down-regulates activity	0.48	Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.\|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase.	SIGNOR-279238
P28222	P09471	1	binding	up-regulates activity	0.48	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-256999
P24863	P46531	1	phosphorylation	down-regulates	0.48	Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.	SIGNOR-130592
Q96J02	P00533	1	polyubiquitination	down-regulates quantity by destabilization	0.48	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-272604
Q16539	P15923	1	phosphorylation	up-regulates activity	0.48	Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription	SIGNOR-134194
P12931	Q9NZC7	1	phosphorylation	up-regulates	0.48	The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.	SIGNOR-123819
Q5H9F3	Q8WUI4	1	binding	up-regulates activity	0.48	BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.	SIGNOR-259114
Q9NTG7	P08559	1	deacetylation	down-regulates activity	0.48	SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells\|SIRT3 deacetylates PDHA1 lysine 321 (K321)	SIGNOR-267636
Q08378	Q9HD26	1	binding	up-regulates activity	0.48	Golgin-160 belongs to the golgin family of Golgi-localized proteins, which have been implicated in Golgi structure and function. PIST (also known as GOPC, CAL, and FIG) has been implicated in the trafficking of a subset of plasma membrane proteins, supporting a role of golgin-160 in vesicular trafficking. binding of golgin-160, TC10, and syntaxin-6 to PIST may coordinate membrane trafficking of some plasma membrane proteins in cell types where these proteins are expressed.	SIGNOR-261234
P42771	P24941	1	binding	down-regulates	0.48	However, induction of p16(ink4a) also causes marked inhibition of cdk2 activity.	SIGNOR-64431
P00533	P48431	1	phosphorylation	up-regulates quantity by stabilization	0.48	These data indicate that EGFR\u2010induced SOX2 Tyr277 phosphorylation prevents the autophagic degradation of SOX2 and enhances its stability.	SIGNOR-279036

P01137

P02452

1

transcriptional regulation

up-regulates quantity by expression

0.485

COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity

SIGNOR-277678

Q5S007

P62841

1

phosphorylation

up-regulates activity

0.485

Taken together, these results suggest that phosphorylation of s15 on T136 by LRRK2 mediates enhanced cap-dependent and cap-independent reporter translation and that a stimulatory effect of LRRK2 on mRNA translation contributes to LRRK2 toxicity.

SIGNOR-279058

P00540

Q02750

1

phosphorylation

up-regulates activity

0.485

Our data indicate that Mos activated MEK1 in vitro as well as in vivo by phosphorylating Ser 222.

SIGNOR-260920

Q13882

Q96P48

1

phosphorylation

up-regulates activity

0.485

ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.

SIGNOR-263188

P32238

P30679

1

binding

up-regulates activity

0.485

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-257410

P17612

Q12972

1

phosphorylation

down-regulates activity

0.484

NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A

SIGNOR-250033

Q05513

P08047

1

phosphorylation

up-regulates

0.484

Here we have used a variety of approaches to identify 3 amino acids (thr668, ser670, and thr681) in the zinc finger domain of sp1 that are modified by pkc-zeta angiotensin ii, which activates pkc-? Phosphorylation (at thr410) via the angiotensin ii type 1 receptor, stimulates sp1 phosphorylation and increases sp1 binding to the platelet-derived growth factor-d promoter.

SIGNOR-160774

Q14164

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.484

The activated ikk complex then phosphorylates ikbalfa (an inhibitor of nf-kb) thereby targeting it for ubiquitination and proteasomal degradation.

SIGNOR-167524

Q9H4A3

O95747

1

phosphorylation

up-regulates

0.484

Activation of wnk1 coincides with the phosphorylation and activation of two wnk1 substrates, namely, the protein kinases ste20/sps1-related proline alanine-rich kinase (spak) and oxidative stress response kinase-1 (osr1)

SIGNOR-151659

P51149

Q8NEB9

1

guanine nucleotide exchange factor

up-regulates activity

0.484

The p150 adapter protein is in a complex with rab7. The hVPS34/p150 complex colocalized with rab7 on late endosomes and hVPS34 activity was dependent on nucleotide cycling of rab7

SIGNOR-261302

Q9UEW8

P55017

1

phosphorylation

down-regulates activity

0.484

SPAK directly phosphorylates NCC and its effects on NCC are universally associated with phosphorylation|This adds to the evidence that SPAK-mediated phosphorylation acts primarily to increase activity of individual cotransporters without affecting the amount of NCC on the surface| the kinase (SPAK) that phosphorylates NCC at T53

SIGNOR-264623

Q9HBW0

O95837

1

binding

up-regulates activity

0.484

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-257431

P03951

P00740

1

cleavage

up-regulates activity

0.484

Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets.

SIGNOR-263537

Q13153

O14950

1

phosphorylation

up-regulates activity

0.484

It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].

SIGNOR-280053

P63151

P31749

1

binding

down-regulates activity

0.484

Regulation of phosphorylation of Thr-308 of Akt, cell proliferation, and survival by the B55alpha regulatory subunit targeting of the protein phosphatase 2A holoenzyme to Akt.|Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural |Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells.subunit (A), catalytic subunit (C), and a variable regulatory subunit (B).

SIGNOR-252637

P61073

P04899

1

binding

up-regulates activity

0.484

Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner

SIGNOR-278103

P06493

Q16659

1

phosphorylation

up-regulates

0.484

Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3. All four sites are followed by a proline residue. We have shown that purified cyclin b-cdk1 (cyclindependent kinase 1) phosphorylates these sitesalanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.

SIGNOR-164499

Q9UI47

P14923

1

relocalization

up-regulates quantity

0.484

Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14

SIGNOR-265494

Q9Y4I1

P63027

1

binding

up-regulates activity

0.484

Another potential role of myosin Va in LDCV exocytosis lies in facilitating the formation of the SNARE complex, which is needed for fusion of the vesicle with the plasma membrane. Notably, myosin Va binds to at least two SNARE proteins in a Ca2+-dependent manner: at micromolar Ca2+-levels, it binds to VAMP2 located in the membrane of the cargo vesicle via its globular tail domain

SIGNOR-269281

P49841

P53805

1

phosphorylation

up-regulates activity

0.484

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249359

P17481

P40426

1

binding

up-regulates activity

0.484

the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.

SIGNOR-223149

Q92765

Q9H1J5

1

binding

down-regulates

0.484

We and others demonstrated that fzb-1 blocks wnt-1 and xwnt-8 signaling in xenopus embryos,

SIGNOR-51798

Q9P2K8

Q9BY44

1

phosphorylation

down-regulates activity

0.484

Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).

SIGNOR-280005

Q6Q0C0

Q99759

1

binding

up-regulates

0.484

Traf7 specifically interacts with and activates mekk3.

SIGNOR-123221

P30679

Q9NQ66

1

binding

up-regulates activity

0.484

This suggests that both Gal4 and Gal6 can activate PLC b1.

SIGNOR-278120

Q9UKC9

P30281

1

binding

down-regulates quantity by destabilization

0.484

Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation.

SIGNOR-271887

O43683

P04637

1

phosphorylation

up-regulates activity

0.484

In addition, purified Bub1 directly phosphorylates p53 on Ser-37 in vitro , possibly inducing cellular senescence [ xref ].|Studies have shown that depletion and inhibition of Aurora A, Aurora B, Plk1, or Bub1 induces cellular senescence or cell death in a p53 dependent or -independent but p73 dependent manner in many different cell types , - ].

SIGNOR-280199

P34925

O14640

1

binding

up-regulates

0.483

Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled.

SIGNOR-129568

O60285

P55212

1

phosphorylation

down-regulates activity

0.483

ARK5 negatively regulates procaspase-6 by phosphorylation at Ser257, leading to resistance to the FasL/Fas system.

SIGNOR-250209

Q86Y13

P54253

1

polyubiquitination

down-regulates quantity by destabilization

0.483

HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation.

SIGNOR-272078

Q9UBY5

P50148

1

binding

up-regulates activity

0.483

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-257297

P14416

P63096

1

binding

up-regulates activity

0.483

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-256701

P49336

Q01094

1

phosphorylation

down-regulates

0.483

E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.

SIGNOR-181078

Q9HCM9

Q96BY2

1

binding

up-regulates quantity by stabilization

0.483

TRIM39 stabilizes MOAP-1 by inhibiting the poly-ubiquitination process of MOAP-1.In this study, we report the identification and characterization of TRIM39 as a binding partner of MOAP-1. TRIM39 is the first regulator of MOAP-1 protein stability identified.

SIGNOR-272911

Q7Z6J4

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.483

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-260552

P62873

Q9NQ66

1

binding

down-regulates

0.483

These results indicate that g-protein beta gamma subunits constitute a mechanism by which g-protein mediate a rapid and transient plc- beta 1.

SIGNOR-44369

P16284

P28907

1

binding

up-regulates activity

0.483

As a receptor, CD38 interacts with its ligand CD31 [15,16]. CD31, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a 130 kDa type I transmembrane glycoprotein that consists of six extracellular immunoglobulin-like homology domains, a 19-residue transmembrane domain, and a 118-residue cytoplasmic tail

SIGNOR-264254

Q8TDC3

P30307

1

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

Q9UKC9

Q96GD4

1

binding

down-regulates quantity by destabilization

0.483

The SCF complex contains a catalytic core consisting of Skp1, Cullin1, and the E2 ubiquitin-conjugating (Ubc) enzyme and a F box component that acts as a receptor targeting numerous substrates via phosphodegron elicited interactions. our screening studies suggested that FBXL2 also targets Aurora B protein for ubiquitination and degradation.

SIGNOR-272097

Q9UGL1

P55771

1

binding

up-regulates activity

0.483

Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression

SIGNOR-223875

P27361

Q92934

1

phosphorylation

down-regulates

0.483

Erk-1 map kinase prevents tnf-induced apoptosis through bad phosphorylation and inhibition of bax translocation in hela cells.

SIGNOR-188172

O43791

Q9UER7

1

ubiquitination

down-regulates quantity

0.483

These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.

SIGNOR-268858

P31749

Q13363

1

phosphorylation

down-regulates quantity

0.483

Co-expression of Pc2 and Akt1 results in both phosphorylation and ubiquitylation of CtBP1, thereby targeting CtBP1 for degradation.|CtBP1 phosphorylation by Akt1 appears to both decrease dimerization and induce ubiquitylation.

SIGNOR-278304

P67775

Q04206

1

dephosphorylation

down-regulates

0.483

Rela was dephosphorylated by a purified pp2a core enzyme, a heterodimer formed by the catalytic subunit of pp2a (pp2ac) and pr65, in a concentration-dependent manner.These data suggest that the constitutive activation of rela in melanoma cells could be due, at least in part, to the deficiency of pp2a, which exhibits decreased dephosphorylation of nf-kappa b/rela.

SIGNOR-110959

P01106

Q13616

1

transcriptional regulation

up-regulates quantity by expression

0.483

Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2

SIGNOR-102749

Q9NYY3

Q969H0

1

phosphorylation

down-regulates

0.483

Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176

SIGNOR-196448

O43303

Q12798

1

binding

up-regulates activity

0.483

We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis.

SIGNOR-265966

Q86UF1

O14672

1

binding

up-regulates activity

0.483

Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.

SIGNOR-261251

Q96EP1

Q14527

1

polyubiquitination

down-regulates quantity by destabilization

0.482

CHFR functions as a ubiquitin ligase for HLTF to regulate its stability and functions. CHFR negatively regulates and ubiquitinates HLTF. Taken together, this is the first report identifying the regulatory mechanism of HLTF by CHFR, suggesting that CHFR-mediated downregulation of HLTF may help protect against cancer.

SIGNOR-271460

P12757

Q15797

1

binding

down-regulates

0.482

Ski also represses bmp signaling through interactions with smad4 and bmp-specific r-smads, smad1 or smad7

SIGNOR-195636

P61244

Q14582

1

binding

up-regulates activity

0.482

the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences.

SIGNOR-240224

P06493

Q8TD19

1

phosphorylation

up-regulates activity

0.482

We now identify Plk1 as Nek9 direct activator and propose a two-step activation mechanism that involves Nek9 sequential phosphorylation by CDK1 and Plk1. while CDK1 activity is necessary for Nek9 phosphorylation in mitosis and the resulting change in electrophoretical mobility, Nek9 Thr210 phosphorylation and mitotic activation requires both CDK1 and Plk1.

SIGNOR-273889

Q16644

Q6JBY9

1

phosphorylation

down-regulates activity

0.482

Human CapZIP was phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. In the present paper we have identified CapZIP as a protein that is phosphorylated exceptionally rapidly by several SAPKs in vitro (Figure 4), and which is expressed in muscles and immune cells. Both MAPKAP-K2 and MAPKAP-K3 phosphorylated CapZIP at Ser-179 in vitro. An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.

SIGNOR-263082

P35637

Q08211

1

relocalization

down-regulates activity

0.482

We found that ALS mutants of FUS co-localized with Caprin-1, DDX3X, and DHX9 in cytoplasmic inclusions that could lead to the mis-regulation of their respective pathways, providing further clues to the mechanism of ALS pathogenesis.|FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. | We also demonstrated the co-localization of DHX9, DDX3X and Caprin-1 with cytoplasmic EGFP-P525L mutant FUS inclusions in primary cortical neurons

SIGNOR-262810

P06748

Q969H0

1

binding

up-regulates quantity

0.482

We report here that NPM regulates turnover of the c-Myc oncoprotein by acting on the F-box protein Fbw7 , a component of the E3 ligase complex involved in the ubiquitination and proteasome degradation of c-Myc. NPM was required for nucleolar localization and stabili- zation of Fbw7

SIGNOR-245084

Q14258

Q13887

1

polyubiquitination

down-regulates quantity by destabilization

0.482

The oestrogen-inducible E3 ligase EFP (oestrogen-responsive finger protein) was identified as a key player in oestrogen-mediated degradation of KLF5, as knockdown and overexpression of EFP increased and decreased KLF5 protein levels respectively, and the decrease continued even when protein synthesis was blocked.

SIGNOR-271908

Q13315

O95863

1

phosphorylation

up-regulates activity

0.482

ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.

SIGNOR-279587

P21918

P63092

1

binding

up-regulates activity

0.482

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-256771

P45984

P40763

1

phosphorylation

up-regulates

0.482

Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

SIGNOR-179275

P27361

P07101

1

phosphorylation

up-regulates

0.482

In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11

SIGNOR-34678

Q9P2G9

Q13702

1

binding

down-regulates quantity by destabilization

0.482

We found that rapsyn was polyubiquitinated by KLHL8-containing E3 ligase, but not by KEAP1-containing E3 ligase, clearly indicating that rapsyn is a direct substrate of KLHL8-containing E3 ligase in mammals. We next examined the effect of KLHL-8 depletion on the ubiquitination of rapsyn by performing RNAi experiments in mammalian cells. We found that knockdown of KLHL8 in 3T3 cells reduced the level of rapsyn ubiquitination (Fig. 5C), again indicating that the maintenance mechanism for rapsyn stability is conserved in mammals.The in vitro ubiquitination of mammalian rapsyn by CUL3-containing E3 ligase and the effect of KLHL8 knockdown on the ubiquitination of rapsyn.

SIGNOR-271781

P53350

P11388

1

phosphorylation

up-regulates

0.481

Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin

SIGNOR-182844

P17252

Q01970

1

phosphorylation

down-regulates

0.481

These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.

SIGNOR-58859

P23470

P00533

1

dephosphorylation

down-regulates activity

0.481

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254699

P49841

Q04721

1

phosphorylation

down-regulates activity

0.481

We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.

SIGNOR-101570

P35548

Q96T58

1

binding

up-regulates

0.481

Furthermore, in addition to msx2, both tlx1 and nkx2-5 proteins interacted with notch-pathway repressors, spen/mint/sharp and tle1/grg1, representing a potential mechanism for (de)regulation.

SIGNOR-188572

Q96SB3

Q96N96

1

binding

up-regulates activity

0.481

Here we show that Asef2, but not Asef, interacts with Neurabin2/Spinophilin, a scaffold protein that binds to Filamentous actin (F-actin). Neurabin2 is required for Asef2-induced filopodia formation. RNA interference experiments showed that Asef2, Neurabin2 and APC are involved in HGF-induced cell migration. Furthermore, knockdown of Neurabin2 resulted in the suppression of Asef2-induced filopodia formation.

SIGNOR-269174

Q00535

P04150

1

phosphorylation

down-regulates activity

0.481

Cdk5 phosphorylated gr at multiple serines, including ser203 and ser211 of its n-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to dna.| the effect of CDK5 on GR-induced transcriptional activity is specific to gene promoter, and possibly, to tissue

SIGNOR-154405

Q00341

P49711

1

binding

up-regulates activity

0.481

Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19. vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of β-globin, and several regions within the Igf2/H19 locus. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.

SIGNOR-266693

Q92793

P10243

1

binding

up-regulates activity

0.481

CBP co-operates functionally with A-Myb

SIGNOR-240984

Q15831

Q9H0K1

1

phosphorylation

up-regulates

0.481

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-122788

P62714

P31751

1

dephosphorylation

down-regulates

0.481

These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity

SIGNOR-42123

Q03060

P60568

1

transcriptional regulation

down-regulates quantity by repression

0.481

In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production.

SIGNOR-261576

P11309

P38936

1

phosphorylation

up-regulates quantity by stabilization

0.481

Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellshere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo

SIGNOR-164642

P09958

P04275

1

cleavage

up-regulates activity

0.481

Like PACE,PACE4 was able to process pro-vWF to its mature form, and efficient cleavage required both the P4 arginine and the P2 lysine

SIGNOR-260368

P43220

P63092

1

binding

up-regulates activity

0.481

The GPCRs are allocated in five families where the GLP-1R and GIPR are found within the secretin family, also classified as class B [31,32]. Upon stimulation by an extracellular stimuli (ligand), GPCRs undergo conformational changes, and triggers downstream intracellular signals by coupling with G proteins (or other intracellular proteins such as arrestins), causing a wide range of both physiological and pathological processes.To stimulate insulin secretion, and in the presence of elevated blood glucose concentrations, GLP-1R activation in pancreatic beta cells promote recruitment and activation of Gαs protein leading to adenylate cyclase-mediated cAMP production, elevation of Ca2+, and ERK1/2 phosphorylation (Fig. 3)

SIGNOR-278137

Q16659

Q9Y6Q9

1

phosphorylation

up-regulates

0.481

Here, we report that erk3 interacted with and phosphorylated steroid receptor coactivator 3 (src-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (s857)

SIGNOR-196957

Q01726

P63092

1

binding

up-regulates activity

0.481

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-268697

P68036

Q6ZMZ0

1

binding

up-regulates activity

0.481

We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and

SIGNOR-271591

P18825

P63096

1

binding

up-regulates activity

0.48

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-256699

Q99835

Q9NRP7

1

binding

up-regulates

0.48

Smo then activates stk36 serine/threonine kinase to stabilize gli family members and to phosphorylate sufu for nuclear accumulation of gli.| sufu binds to the kinesin cos2 to transduce the hh signal downstream of smo

SIGNOR-150540

Q9UMS4

P15927

1

polyubiquitination

up-regulates activity

0.48

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). PRP19 ubiquitylates RPA and promotes ATRIP recruitment.

SIGNOR-272075

P42338

P49841

1

phosphorylation

down-regulates activity

0.48

In our cultures, both p110alpha and p110beta phosphorylated GSK-3beta at Ser9 confirming previous data.|Whereas p110alpha reduced the protein levels of the CDK2-inhibitor p27 Kip1, p110beta phosphorylated and inactivated GSK-3beta.

SIGNOR-279089

P42229

Q9BZS1

1

null

up-regulates

0.48

We demonstrate that the signal transducer and activator of transcription 5 (STAT5)-signaling cytokines, IL-2, IL-15 and to a lesser extent IL-7, induce FOXP3 up-regulation in vitro in activated human Teff cell

SIGNOR-254301

Q12841

Q14689

1

binding

up-regulates activity

0.48

We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. The work in the current study identifies DIP2A as a novel receptor for FSTL1 that mediates Akt activation and cell survival and function in cardiovascular cells in vitro.

SIGNOR-266603

P28482

Q8IW41

1

phosphorylation

up-regulates

0.48

Activated following phosphorylation at thr-182 by p38-alpha/mapk14, p38-beta/mapk11, erk2/mapk1, erk3/mapk6, and erk4/mapk4.

SIGNOR-58127

Q5S007

Q92997

1

binding

up-regulates

0.48

Subsequent assays confirmed a direct interaction between the lrrk2 roccor domain and all three human dvl proteins, these data are consistent with a role for lrrk2 in the activation of canonical wnt signaling bringing dvl proteins to cellular membranes.

SIGNOR-202187

Q13131

P04637

1

phosphorylation

up-regulates

0.48

Ampk activation induces phosphorylation of p53 on serine 15, and this phosphorylation is required to initiate ampk-dependent cell-cycle arrest

SIGNOR-135960

P12931

O60500

1

phosphorylation

up-regulates activity

0.48

Inhibition of Src kinase dependent Nephrin phosphorylation achieved by incubation of WT-Nephrin-overexpressing cells with 1 mum PP2 abolished the positive effect of Nephrin on GSIR (XREF_FIG D).|We were able to demonstrate a complete prevention of Nephrin phosphorylation, confirming that Nephrin phosphorylation is mediated by Src.

SIGNOR-280129

Q8IY84

P30291

1

phosphorylation

down-regulates activity

0.48

Furthermore, purified bacterially produced Nim1 kinase directly phosphorylates and inactivates Wee1 in vitro.|Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1 and cdr1 kinase.

SIGNOR-279238

P28222

P09471

1

binding

up-regulates activity

0.48

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-256999

P24863

P46531

1

phosphorylation

down-regulates

0.48

Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.

SIGNOR-130592

Q96J02

P00533

1

polyubiquitination

down-regulates quantity by destabilization

0.48

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-272604

Q16539

P15923

1

phosphorylation

up-regulates activity

0.48

Here we show that p38 mapk, whose activity is essential for myogenesis, regulates myod/e47 heterodimerization. Phosphorylation of e47 at ser140 by p38 induces myod/e47 association and activation of muscle-specific transcription

SIGNOR-134194

P12931

Q9NZC7

1

phosphorylation

up-regulates

0.48

The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.

SIGNOR-123819

Q5H9F3

Q8WUI4

1

binding

up-regulates activity

0.48

BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.

SIGNOR-259114

Q9NTG7

P08559

1

deacetylation

down-regulates activity

0.48

SIRT3 deacetylates and increases pyruvate dehydrogenase activity in cancer cells|SIRT3 deacetylates PDHA1 lysine 321 (K321)

SIGNOR-267636

Q08378

Q9HD26

1

binding

up-regulates activity

0.48

Golgin-160 belongs to the golgin family of Golgi-localized proteins, which have been implicated in Golgi structure and function. PIST (also known as GOPC, CAL, and FIG) has been implicated in the trafficking of a subset of plasma membrane proteins, supporting a role of golgin-160 in vesicular trafficking. binding of golgin-160, TC10, and syntaxin-6 to PIST may coordinate membrane trafficking of some plasma membrane proteins in cell types where these proteins are expressed.

SIGNOR-261234

P42771

P24941

1

binding

down-regulates

0.48

However, induction of p16(ink4a) also causes marked inhibition of cdk2 activity.

SIGNOR-64431

P00533

P48431

1

phosphorylation

up-regulates quantity by stabilization

0.48

These data indicate that EGFR\u2010induced SOX2 Tyr277 phosphorylation prevents the autophagic degradation of SOX2 and enhances its stability.

SIGNOR-279036