GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P20339	Q9UH99	binding	up-regulates activity	0.42	Rab5ip represents a novel rab5 interacting protein that may function on endocytic vesicles as a receptor for rab5-GDP and participate in the activation of rab5	SIGNOR-261309
P36888	P11309	phosphorylation	up-regulates quantity	0.42	Pim-1 Kinase Phosphorylates and Stabilizes 130 kDa FLT3 and Promotes Aberrant STAT5 Signaling in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication[...]Pim-1 inhibition also decreased phosphorylation of FLT3 at tyrosine 591 and of STAT5, and expression of Pim-1 itself, consistent with inhibition of the FLT3-ITD-STAT5 signaling pathway.	SIGNOR-259927
Q7L804	Q7KZI7	phosphorylation	up-regulates	0.42	We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.	SIGNOR-147118
Q8N5V2	Q00535	phosphorylation	up-regulates activity	0.42	Importantly, ephexin1, a Rho GEF, is phosphorylated by Cdk5 in vivo .	SIGNOR-279021
Q8NEB9	P06493	phosphorylation	down-regulates	0.42	We show that vps34 is phosphorylated on thr159 by cdk1, thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy	SIGNOR-165768
Q9Y6R4	O15169	binding	up-regulates	0.42	Mekk4, also binds to axin in vivo and mediates axin-induced jnk activation.	SIGNOR-104003
Q9BUB5	Q13177	phosphorylation	down-regulates activity	0.42	Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. When 293T cells are subjected to apoptotic induction by hydrogen peroxide, Mnk1 is phosphorylated at both Thr(22) and Ser(27). These results indicate a role for Pak2 in the down-regulation of translation initiation in apoptosis by phosphorylation of Mnk1.	SIGNOR-250221
O14641	P34925	binding	up-regulates	0.419	Ryk also binds to dishevelled, through which it activates the canonical wnt, providing a link between wnt and dishevelled.	SIGNOR-129571
P10636	Q96L34	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273935
P42261	P46934	ubiquitination	down-regulates quantity	0.419	Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature.\|The ability of Nedd4-1 to reduce surface GluA1 levels required its ligase activity, since co-expression of a catalytically-inactive version of Nedd4-1 (Nedd4-1 CS) did not decrease surface GluA1 levels .	SIGNOR-278572
P12931	Q8TEW6	binding	up-regulates	0.419	Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.	SIGNOR-101002
P00533	P00519	phosphorylation	up-regulates	0.419	we show that activated Abl phosphorylates the EGFR primarily on tyrosine 1173Furthermore, we show that activated Abl allows the ligand-activated EGFR to escape Cbl-dependent down-regulation by inhibiting the accumulation of Cbl at the plasma membrane in response to epidermal growth factor stimulation and disrupting the formation of the EGFR.Cbl complex without affecting Cbl protein stability. These findings reveal a novel role for Abl in promoting increased cell-surface expression of the EGFR and suggest that Abl/EGFR signaling may cooperate in human	SIGNOR-149277
O15297	Q9H2X6	phosphorylation	down-regulates quantity by destabilization	0.419	HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels.	SIGNOR-278230
P10636-5	Q96L34	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273932
Q96NT3	P46934	polyubiquitination	down-regulates quantity by destabilization	0.419	The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.	SIGNOR-272846
Q6JBY9	O15264	phosphorylation	down-regulates activity	0.419	CapZIP was also phosphorylated rapidly by SAPK3/p38γ and SAPK4/p38δ, and even faster and more extensively by JNK1α1, these protein kinases phosphorylating CapZIP in vitro to >3, approx. 2 and >5 mol of phosphate/mol of protein respectively within a few minutes. Following tryptic digestion and C18 chromatography, further sites phosphorylated by JNK1α1 were identified as Ser-68, Ser-83 and Ser-216 (results not shown), and are highlighted in Figure 3.Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown).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-263084
Q9UMX1	Q9UF56	ubiquitination	down-regulates quantity by destabilization	0.419	Here, we show that Fbxl17 (F-box and leucine-rich repeat protein 17) targets Sufu for proteolysis in the nucleus. The ubiquitylation of Sufu, mediated by Fbxl17, allows the release of Gli1 from Sufu for proper Hh signal transduction	SIGNOR-253545
O15554	P22392	phosphorylation	up-regulates	0.419	We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.	SIGNOR-181083
P46527	Q13315	phosphorylation	up-regulates quantity by stabilization	0.419	We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.	SIGNOR-279392
P01116	P49356	null	up-regulates activity	0.419	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242556
P35222	P19793	binding	down-regulates	0.419	Rxr agonists still inactivated endogenous beta-catenin via rxr alpha.	SIGNOR-101293
Q14493	P06493	phosphorylation	down-regulates quantity by destabilization	0.419	Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase	SIGNOR-265258
O95239	O14965	phosphorylation	up-regulates activity	0.419	We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).	SIGNOR-265993
Q9NZN5	P50148	binding	up-regulates activity	0.419	Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA.	SIGNOR-256520
P08754	Q9H1C0	binding	up-regulates activity	0.419	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-256861
P49841	Q5JTC6	relocalization	up-regulates activity	0.419	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171892
Q8IY63	Q9P2P5	ubiquitination	up-regulates activity	0.419	These results clearly indicate that HECW2 ubiquitinates AMOTL1 with K63-linked polyubiquitin chains.\|Unlike NEDD4.2, HECW2 targeted AMOTL1 and promoted its stability.	SIGNOR-278811
Q9UQL6	Q14012	phosphorylation	down-regulates	0.419	Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.	SIGNOR-85022
Q14934	P45984	phosphorylation	up-regulates activity	0.419	Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.\|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2.	SIGNOR-280036
Q13485	P27361	phosphorylation	up-regulates	0.419	Our results suggest that map kinase can phosphorylate thr276 of smad4 and that phosphorylation can lead to enhanced tgf-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of smad4.	SIGNOR-101664
Q8IZP0	P06493	phosphorylation	down-regulates activity	0.419	We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis.\|Bcr-Abl-induced actin polymerization requires the Abi1 pathway, as the blockade of the signal transduction from Bcr-Abl to Abi1 abolishes the F-actin assembly\|serine phosphorylation of Abi1 by CDK1/cyclin B serves as a cell cycle-dependent regulatory mechanism that inhibits actin assembly	SIGNOR-264421
P10636-4	Q96L34	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273934
P62736	P01137	transcriptional regulation	up-regulates quantity by expression	0.419	A TGF-β1 response element that has a sequence different to that known for Smad binding has been identified in the α- SM actin promoter and seems to be essential for expression of α-SM actin in both SM cells 72 and myofibroblasts73 . How TGF-β1 activates expression of α-SM actin through this TGF-β1 control element is, as yet, unknown	SIGNOR-277681
Q12778	P48729	phosphorylation	down-regulates	0.418	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183658
P13631	P50613	phosphorylation	up-regulates activity	0.418	RARg Is Phosphorylated by cdk7 in Its B and F Regions \| Mutation into alanine of Ser-77 and Ser-79 located in the A/B region reduced the transcriptional activity of hRARg1 (Fig. 9A), confirming that these phosphorylation sites are required for optimal transcription.	SIGNOR-259853
P27448	P11309	phosphorylation	down-regulates	0.418	Here we show that the protein kinase cdc25 c-associated kinase 1 (c-tak1) is a binding partner and a substrate of pim-1.	SIGNOR-128264
P11137	Q9P0L2	phosphorylation	down-regulates activity	0.418	Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.	SIGNOR-250166
Q16236	P05771	phosphorylation	up-regulates	0.418	Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress	SIGNOR-91830
P42338	Q6ZUJ8	binding	up-regulates	0.418	This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.	SIGNOR-191667
Q96S44	Q96KB5	phosphorylation	up-regulates activity	0.418	In this study, we provide evidence showing that TOPK promotes metastasis of colorectal carcinoma, which is mediated through its phosphorylation of PRPK at Ser250.\|Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK.	SIGNOR-278236
O14746	P12931	phosphorylation	down-regulates	0.418	Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707	SIGNOR-102097
Q9Y463	Q96S59	binding	down-regulates activity	0.418	Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M.	SIGNOR-238008
Q92547	Q8IYD8	relocalization	up-regulates	0.418	The enzymatic activity of fan cm is then required to remodel and stabilize the fork to allow topbp1 access to activate atr , in a 9-1-1-independent manner.	SIGNOR-164765
Q6N021	O60674	phosphorylation	up-regulates activity	0.418	Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin.	SIGNOR-277289
O15182	O43303	binding	up-regulates activity	0.418	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-265968
P27695	Q03468	binding	down-regulates activity	0.418	CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced (up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity.	SIGNOR-251932
P35579	P26447	binding	down-regulates activity	0.418	Our results show that S100A4 regulates cell polarization during directed motility by affecting the localization of protrusions through interactions with myosin-IIA, with S100A4 expressing cells displaying few side protrusions and extensive forward protrusions during chemotaxis compared with control cells. The mechanisms by which these antibodies and S100A4 increase protrusive activity and promote cellular motility are not well understood, but the observation that S100A4 can inhibit the actin-activated ATPase of myosin-IIA (34) suggests that S100A4 could function as a myosin-IIA inhibitor in vivo.	SIGNOR-269282
P49916	P24941	phosphorylation	down-regulates	0.418	Dna ligase iii_ is specifically phosphorylated in replicating cells by the cell cycle kinase cdk2. However, in response to oxidative dna damage, dna ligase iii_ is dephosphorylated in a pathway that is dependent upon the dna damage-activated, phosphatidylinositol 3-phosphate (pi3)1-related kinase atm.	SIGNOR-150121
P63096	P32249	binding	up-regulates activity	0.418	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-256715
P35968	P18031	dephosphorylation	down-regulates activity	0.418	This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y 1175 , the site involved in activating ERK signaling.	SIGNOR-277011
P43405	Q92835	dephosphorylation	down-regulates activity	0.418	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268456
Q14451	P06213	binding	up-regulates	0.418	Insulin induces the ir-grb7 interaction in cells expressing physiological levels of the proteins, suggesting that grb7 is implicated in insulin signaling.	SIGNOR-77153
Q6UUV7	P57059	phosphorylation	down-regulates	0.418	These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.	SIGNOR-147703
Q01844	Q15637	binding	down-regulates	0.418	Here we report that zfm1 also interacts withews / overexpression of zfm1 in hepg2 cells represses the transactivation of reporter gene expression driven by gal4-ews-ntd fusion protein and this repression correlates with zfm1 binding to ews.	SIGNOR-58928
P38936	Q9NRM7	phosphorylation	down-regulates quantity	0.417	Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis.\|Subsequently, Lats2 phosphorylates p21 at S146.	SIGNOR-279530
P30304	Q8NG66	phosphorylation	down-regulates	0.417	Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites	SIGNOR-187867
O96020	Q9HCK8	transcriptional regulation	up-regulates quantity by expression	0.417	In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes.	SIGNOR-268804
P17252	O15530	phosphorylation	up-regulates	0.417	One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.	SIGNOR-126066
Q05586	P17252	phosphorylation	up-regulates activity	0.417	Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.	SIGNOR-263177
Q15306	O75116	phosphorylation	up-regulates	0.417	Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.	SIGNOR-167471
P43354	P28702	binding	up-regulates	0.417	The recent discovery that the nuclear transcription factor, nurr1, in heterodimeric tandem with rxr, is unequivocally necessary for the expression of dopaminergic neurons	SIGNOR-58309
O14965	Q13153	phosphorylation	up-regulates	0.417	The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability	SIGNOR-205110
P46934-4	P12931	phosphorylation	up-regulates activity	0.417	Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4.	SIGNOR-276860
Q9NRY4	P23471	dephosphorylation	down-regulates activity	0.417	Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP\| Furthermore, Ptprz selectively dephosphorylated pY1105 of p190 RhoGAP in vitro, and the tyrosine phosphorylation at Y1105 controls p190 RhoGAP activity in vivo.	SIGNOR-248451
Q15746	P12931	phosphorylation	up-regulates	0.417	Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.	SIGNOR-85009
Q06330	Q96K30	binding	down-regulates	0.417	Thus, we propose that rita acts as a negative modulator of the notch signalling pathway, controlling the level of nuclear rbp-j/cbf-1, where its amounts are limiting.	SIGNOR-170089
P29320	P18031	dephosphorylation	down-regulates activity	0.417	Nevertheless, the finding that phosphorylation of the activation loop tyrosine (EphA3-Y779), a recently identified PTP1B substrate (Mertins et al., 2008), is essential for ligand-induced endocytosis (Janes et al., 2009)	SIGNOR-248426
P42336	P16144	binding	up-regulates	0.417	Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation.	SIGNOR-54530
Q92831	P78527	phosphorylation	up-regulates activity	0.417	In response to UV-induced DNA damage, DNA-PK phosphorylates and activates PCAF, and activated PCAF is transferred to photo lesion sites and further acetylates RPA1 at K163.	SIGNOR-280092
P04637	Q13627	phosphorylation	up-regulates	0.417	Dyrk1a phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. we found that dyrk1a phosphorylates p53 at ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor h19-7 cells. In addition, dyrk1a-induced p53 phosphorylation at ser-15 led to a robust induction of p53 target genes	SIGNOR-167407
Q06945	Q01344	binding	up-regulates activity	0.417	Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation.	SIGNOR-223010
P10243	P19338	binding	down-regulates activity	0.417	We identify nucleolin as one of the nuclear polypeptides that interact specifically with the A-Myb and c-Myb. We show that the interaction of nucleolin with Myb is functional because co-transfection of nucleolin down-regulates Myb transcriptional activity.	SIGNOR-221233
Q9H444	Q6DKK2	binding	up-regulates activity	0.417	We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B.	SIGNOR-265541
P46940	O75122	binding	up-regulates activity	0.416	IQGAP1 is a novel CLASP2-interacting protein\| nonphosphorylated CLASP2 on microtubules is allowed to associate with IQGAP1 for the coupling of microtubules to actin filaments at the front of migrating cells.	SIGNOR-264828
O75369	Q96Q27	binding	down-regulates quantity by destabilization	0.416	Here, we provide the first evidence that a novel ASB2 isoform, ASB2beta, is important for muscle differentiation. ASB2beta is expressed in muscle cells during embryogenesis and in adult tissues. ASB2beta is part of an active E3 ubiquitin ligase complex and targets the actin-binding protein filamin B (FLNb) for proteasomal degradation. Altogether, our results indicated that ASB2β can assemble with elongin B, elongin C, Cullin 5 and Rbx2 to reconstitute an active E3 ubiquitin ligase complex.ASB2β induces polyubiquitylation of FLNb.	SIGNOR-271795
Q96E17	Q86UR5	relocalization	up-regulates activity	0.416	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264382
Q8IU85	Q8N5S9	phosphorylation	up-regulates activity	0.416	CaM-KIdelta exhibits Ca(2+)/CaM-dependent activity that is enhanced (approximately 30-fold) in vitro by phosphorylation of its Thr180 by CaM-K kinase (CaM-KK)alpha, consistent with detection of CaM-KIdelta-activating activity in HeLa cells. \| This sustained activation of CaM-KIdelta was completely abolished by Thr180Ala mutation and inhibited by CaM-KK inhibitor, STO-609, indicating a functional CaM-KK/CaM-KIdelta cascade in HeLa cells.	SIGNOR-250715
Q9Y6K9	P12931	phosphorylation	down-regulates activity	0.416	Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.	SIGNOR-276370
P53350	P60510	dephosphorylation	down-regulates activity	0.416	PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells.	SIGNOR-277076
Q9Y618	O15111	phosphorylation	down-regulates	0.416	Nf-kappab transcription requires ikkalpha to phosphorylate smrt on chromatin, stimulating the exchange of corepressor for coactivator complexes. Ikk directly phosphorylates smrt to stimulate nuclear export. Ikkalpha orchestrates smrt derepression, a prerequisite for nf-kappab transcription and survival.	SIGNOR-129956
O00329	P21860	binding	up-regulates	0.416	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146867
P55087	P68400	phosphorylation	down-regulates activity	0.416	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250827
P01116	P52306	binding	up-regulates	0.416	Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob	SIGNOR-171415
P09651	Q9UBS0	phosphorylation	up-regulates activity	0.416	Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export.	SIGNOR-279569
P41594	P17252	phosphorylation	up-regulates activity	0.416	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249278
P01148	Q9H1B7	transcriptional regulation	up-regulates quantity by expression	0.416	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-267154
P08254	Q9UGU0	transcriptional regulation	up-regulates quantity by expression	0.416	This result indicates that expression of SPBP is sufficient to transactivate a minimal promoter containing a single copy of the SPRE, as well as the full-length stromelysin promoter.	SIGNOR-266223
P27695	Q00987	ubiquitination	down-regulates quantity by destabilization	0.416	Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.	SIGNOR-278555
P55075	P19622	transcriptional regulation	down-regulates quantity by repression	0.416	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.	SIGNOR-265801
Q05193	Q13627	phosphorylation	down-regulates	0.416	Mnb/dyrk1a was shown to phosphorylate dynamin 1 and alter its interactions with several sh3 domain-containing endocytic accessory proteins.Phosphorylation At s795 and s857 was confirmed in full-length dynamin 1, and s857 was subsequently determined to be the major mnb/dyrk1a phosphorylation site in vitro. Phosphorylation at s857 was demonstrated to be the basis for altering the binding of dynamin 1 to amphiphysin 1 and grb 2 by site-directed mutants mimicking phosphorylation.	SIGNOR-127440
O43734	Q14164	phosphorylation	up-regulates activity	0.416	IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.	SIGNOR-262883
Q13882	P60484	dephosphorylation	down-regulates activity	0.416	PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.\|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.	SIGNOR-276975
P42336	Q6ZUJ8	binding	up-regulates	0.416	This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.	SIGNOR-191664
Q16539	O00206	phosphorylation	up-regulates activity	0.416	Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-κB. Activation of neutrophils by S100A9 also proceeds via p38 MAPK, JNK, and ERK1/2 phosphorylation.	SIGNOR-263652
P08581	O15409	transcriptional regulation	down-regulates quantity by repression	0.416	FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk.	SIGNOR-269054
P50542	P62837	ubiquitination	down-regulates quantity by destabilization	0.416	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253023
P00519	Q13177	phosphorylation	down-regulates	0.415	The interaction of c-abl with the abl interactor protein abi2 is shown to be negatively regulated by phosphorylation of serines 637 and 638. These serines are adjacent to the pxxp motif (ptppkrs637s638sfr) that binds the sh3 domain of abi. phosphorylation of c-abl by pak2 inhibits the interaction between the sh3 domain of abi2 and the pxxp motif of c-abl.	SIGNOR-160215
Q13153	Q8N1N5	binding	up-regulates	0.415	We further found that cripak interacted with pak1 through the n-terminal regulatory domain and inhibited pak1 kinase in both in vitro and in vivo assays.	SIGNOR-141467
P63096	Q9H1C0	binding	up-regulates activity	0.415	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-256718
Q9NS91	O76064	binding	up-regulates	0.415	Rnf8 depletion also significantly reduced the accumulation of rad18 to chromatin fraction after ir	SIGNOR-185593

P20339

Q9UH99

0

binding

up-regulates activity

0.42

Rab5ip represents a novel rab5 interacting protein that may function on endocytic vesicles as a receptor for rab5-GDP and participate in the activation of rab5

SIGNOR-261309

P36888

P11309

0

phosphorylation

up-regulates quantity

0.42

Pim-1 Kinase Phosphorylates and Stabilizes 130 kDa FLT3 and Promotes Aberrant STAT5 Signaling in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication[...]Pim-1 inhibition also decreased phosphorylation of FLT3 at tyrosine 591 and of STAT5, and expression of Pim-1 itself, consistent with inhibition of the FLT3-ITD-STAT5 signaling pathway.

SIGNOR-259927

Q7L804

Q7KZI7

0

phosphorylation

up-regulates

0.42

We identified the kinase that phosphorylated rab11-fip2 as mark2/emk1/par-1balpha (mark2), and recombinant mark2 phosphorylated rab11-fip2 only on serine 227. In calcium switch assays, cells expressing rab11-fip2(s227a) showed a defect in the timely reestablishment of p120-containing junctional complexes.

SIGNOR-147118

Q8N5V2

Q00535

0

phosphorylation

up-regulates activity

0.42

Importantly, ephexin1, a Rho GEF, is phosphorylated by Cdk5 in vivo .

SIGNOR-279021

Q8NEB9

P06493

0

phosphorylation

down-regulates

0.42

We show that vps34 is phosphorylated on thr159 by cdk1, thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy

SIGNOR-165768

Q9Y6R4

O15169

0

binding

up-regulates

0.42

Mekk4, also binds to axin in vivo and mediates axin-induced jnk activation.

SIGNOR-104003

Q9BUB5

Q13177

0

phosphorylation

down-regulates activity

0.42

Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. When 293T cells are subjected to apoptotic induction by hydrogen peroxide, Mnk1 is phosphorylated at both Thr(22) and Ser(27). These results indicate a role for Pak2 in the down-regulation of translation initiation in apoptosis by phosphorylation of Mnk1.

SIGNOR-250221

O14641

P34925

0

binding

up-regulates

0.419

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

SIGNOR-129571

P10636

Q96L34

0

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273935

P42261

P46934

0

ubiquitination

down-regulates quantity

0.419

Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature.|The ability of Nedd4-1 to reduce surface GluA1 levels required its ligase activity, since co-expression of a catalytically-inactive version of Nedd4-1 (Nedd4-1 CS) did not decrease surface GluA1 levels .

SIGNOR-278572

P12931

Q8TEW6

0

binding

up-regulates

0.419

Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.

SIGNOR-101002

P00533

P00519

0

phosphorylation

up-regulates

0.419

we show that activated Abl phosphorylates the EGFR primarily on tyrosine 1173Furthermore, we show that activated Abl allows the ligand-activated EGFR to escape Cbl-dependent down-regulation by inhibiting the accumulation of Cbl at the plasma membrane in response to epidermal growth factor stimulation and disrupting the formation of the EGFR.Cbl complex without affecting Cbl protein stability. These findings reveal a novel role for Abl in promoting increased cell-surface expression of the EGFR and suggest that Abl/EGFR signaling may cooperate in human

SIGNOR-149277

O15297

Q9H2X6

0

phosphorylation

down-regulates quantity by destabilization

0.419

HIPK2 phosphorylates WIP1 at Ser54 and Ser85, and phosphorylated WIP1 is subject to proteasomal degradation so that WIP1 is maintained at low levels.

SIGNOR-278230

P10636-5

Q96L34

0

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273932

Q96NT3

P46934

0

polyubiquitination

down-regulates quantity by destabilization

0.419

The E3 ligase NEDD4 regulates GUCD1 degradation. many polyubiquitinylated species of GUCD1 appeared as high molecular weight forms, suggesting that GUCD1 is degraded by the proteasome, after polyubiquitin chain formation, in the presence of NEDD4-1.

SIGNOR-272846

Q6JBY9

O15264

0

phosphorylation

down-regulates activity

0.419

CapZIP was also phosphorylated rapidly by SAPK3/p38γ and SAPK4/p38δ, and even faster and more extensively by JNK1α1, these protein kinases phosphorylating CapZIP in vitro to >3, approx. 2 and >5 mol of phosphate/mol of protein respectively within a few minutes. Following tryptic digestion and C18 chromatography, further sites phosphorylated by JNK1α1 were identified as Ser-68, Ser-83 and Ser-216 (results not shown), and are highlighted in Figure 3.Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown).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-263084

Q9UMX1

Q9UF56

0

ubiquitination

down-regulates quantity by destabilization

0.419

Here, we show that Fbxl17 (F-box and leucine-rich repeat protein 17) targets Sufu for proteolysis in the nucleus. The ubiquitylation of Sufu, mediated by Fbxl17, allows the release of Gli1 from Sufu for proper Hh signal transduction

SIGNOR-253545

O15554

P22392

0

phosphorylation

up-regulates

0.419

We previously showed that nucleoside diphosphate kinase beta (ndpk-b), a mammalian histidine kinase, is required for kca3.1 channel activation in human cd4 t lymphocytes.

SIGNOR-181083

P46527

Q13315

0

phosphorylation

up-regulates quantity by stabilization

0.419

We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.

SIGNOR-279392

P01116

P49356

0

null

up-regulates activity

0.419

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242556

P35222

P19793

0

binding

down-regulates

0.419

Rxr agonists still inactivated endogenous beta-catenin via rxr alpha.

SIGNOR-101293

Q14493

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.419

Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase

SIGNOR-265258

O95239

O14965

0

phosphorylation

up-regulates activity

0.419

We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).

SIGNOR-265993

Q9NZN5

P50148

0

binding

up-regulates activity

0.419

Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA.

SIGNOR-256520

P08754

Q9H1C0

0

binding

up-regulates activity

0.419

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-256861

P49841

Q5JTC6

0

relocalization

up-regulates activity

0.419

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171892

Q8IY63

Q9P2P5

0

ubiquitination

up-regulates activity

0.419

These results clearly indicate that HECW2 ubiquitinates AMOTL1 with K63-linked polyubiquitin chains.|Unlike NEDD4.2, HECW2 targeted AMOTL1 and promoted its stability.

SIGNOR-278811

Q9UQL6

Q14012

0

phosphorylation

down-regulates

0.419

Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.

SIGNOR-85022

Q14934

P45984

0

phosphorylation

up-regulates activity

0.419

Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2.

SIGNOR-280036

Q13485

P27361

0

phosphorylation

up-regulates

0.419

Our results suggest that map kinase can phosphorylate thr276 of smad4 and that phosphorylation can lead to enhanced tgf-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of smad4.

SIGNOR-101664

Q8IZP0

P06493

0

phosphorylation

down-regulates activity

0.419

We identified serine 216 of Abi1 as a target of CDK1/cyclin B kinase that is phosphorylated in cells at the onset of mitosis.|Bcr-Abl-induced actin polymerization requires the Abi1 pathway, as the blockade of the signal transduction from Bcr-Abl to Abi1 abolishes the F-actin assembly|serine phosphorylation of Abi1 by CDK1/cyclin B serves as a cell cycle-dependent regulatory mechanism that inhibits actin assembly

SIGNOR-264421

P10636-4

Q96L34

0

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273934

P62736

P01137

0

transcriptional regulation

up-regulates quantity by expression

0.419

A TGF-β1 response element that has a sequence different to that known for Smad binding has been identified in the α- SM actin promoter and seems to be essential for expression of α-SM actin in both SM cells 72 and myofibroblasts73 . How TGF-β1 activates expression of α-SM actin through this TGF-β1 control element is, as yet, unknown

SIGNOR-277681

Q12778

P48729

0

phosphorylation

down-regulates

0.418

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity

SIGNOR-183658

P13631

P50613

0

phosphorylation

up-regulates activity

0.418

RARg Is Phosphorylated by cdk7 in Its B and F Regions | Mutation into alanine of Ser-77 and Ser-79 located in the A/B region reduced the transcriptional activity of hRARg1 (Fig. 9A), confirming that these phosphorylation sites are required for optimal transcription.

SIGNOR-259853

P27448

P11309

0

phosphorylation

down-regulates

0.418

Here we show that the protein kinase cdc25 c-associated kinase 1 (c-tak1) is a binding partner and a substrate of pim-1.

SIGNOR-128264

P11137

Q9P0L2

0

phosphorylation

down-regulates activity

0.418

Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability.

SIGNOR-250166

Q16236

P05771

0

phosphorylation

up-regulates

0.418

Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress

SIGNOR-91830

P42338

Q6ZUJ8

0

binding

up-regulates

0.418

This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.

SIGNOR-191667

Q96S44

Q96KB5

0

phosphorylation

up-regulates activity

0.418

In this study, we provide evidence showing that TOPK promotes metastasis of colorectal carcinoma, which is mediated through its phosphorylation of PRPK at Ser250.|Therefore, we conclude that TOPK directly promotes metastasis of colorectal cancer by modulating PRPK.

SIGNOR-278236

O14746

P12931

0

phosphorylation

down-regulates

0.418

Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via src kinase family-dependent phosphorylation of tyrosine 707

SIGNOR-102097

Q9Y463

Q96S59

0

binding

down-regulates activity

0.418

Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein M.

SIGNOR-238008

Q92547

Q8IYD8

0

relocalization

up-regulates

0.418

The enzymatic activity of fan cm is then required to remodel and stabilize the fork to allow topbp1 access to activate atr , in a 9-1-1-independent manner.

SIGNOR-164765

Q6N021

O60674

0

phosphorylation

up-regulates activity

0.418

Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin.

SIGNOR-277289

O15182

O43303

0

binding

up-regulates activity

0.418

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-265968

P27695

Q03468

0

binding

down-regulates activity

0.418

CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced (up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity.

SIGNOR-251932

P35579

P26447

0

binding

down-regulates activity

0.418

Our results show that S100A4 regulates cell polarization during directed motility by affecting the localization of protrusions through interactions with myosin-IIA, with S100A4 expressing cells displaying few side protrusions and extensive forward protrusions during chemotaxis compared with control cells. The mechanisms by which these antibodies and S100A4 increase protrusive activity and promote cellular motility are not well understood, but the observation that S100A4 can inhibit the actin-activated ATPase of myosin-IIA (34) suggests that S100A4 could function as a myosin-IIA inhibitor in vivo.

SIGNOR-269282

P49916

P24941

0

phosphorylation

down-regulates

0.418

Dna ligase iii_ is specifically phosphorylated in replicating cells by the cell cycle kinase cdk2. However, in response to oxidative dna damage, dna ligase iii_ is dephosphorylated in a pathway that is dependent upon the dna damage-activated, phosphatidylinositol 3-phosphate (pi3)1-related kinase atm.

SIGNOR-150121

P63096

P32249

0

binding

up-regulates activity

0.418

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-256715

P35968

P18031

0

dephosphorylation

down-regulates activity

0.418

This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y 1175 , the site involved in activating ERK signaling.

SIGNOR-277011

P43405

Q92835

0

dephosphorylation

down-regulates activity

0.418

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268456

Q14451

P06213

0

binding

up-regulates

0.418

Insulin induces the ir-grb7 interaction in cells expressing physiological levels of the proteins, suggesting that grb7 is implicated in insulin signaling.

SIGNOR-77153

Q6UUV7

P57059

0

phosphorylation

down-regulates

0.418

These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.

SIGNOR-147703

Q01844

Q15637

0

binding

down-regulates

0.418

Here we report that zfm1 also interacts withews / overexpression of zfm1 in hepg2 cells represses the transactivation of reporter gene expression driven by gal4-ews-ntd fusion protein and this repression correlates with zfm1 binding to ews.

SIGNOR-58928

P38936

Q9NRM7

0

phosphorylation

down-regulates quantity

0.417

Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis.|Subsequently, Lats2 phosphorylates p21 at S146.

SIGNOR-279530

P30304

Q8NG66

0

phosphorylation

down-regulates

0.417

Nek11 regulates cdc25a degradation and the ir-induced g2/m checkpointincubation of wild-type cdc25a with nek11 led to a marked increase in phosphorylation of ser 82 and 88 as detected with the phosphospecific antibody recognizing these sites

SIGNOR-187867

O96020

Q9HCK8

0

transcriptional regulation

up-regulates quantity by expression

0.417

In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes.

SIGNOR-268804

P17252

O15530

0

phosphorylation

up-regulates

0.417

One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.

SIGNOR-126066

Q05586

P17252

0

phosphorylation

up-regulates activity

0.417

Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890.

SIGNOR-263177

Q15306

O75116

0

phosphorylation

up-regulates

0.417

Carock2 phosphorylated irf4 at either of 2 distinct phosphorylation sites, s446 and s447 / rock2-mediated phosphorylation of irf4 regulated the synthesis of il-17 and il-21 and the differentiation of th17 cells.

SIGNOR-167471

P43354

P28702

0

binding

up-regulates

0.417

The recent discovery that the nuclear transcription factor, nurr1, in heterodimeric tandem with rxr, is unequivocally necessary for the expression of dopaminergic neurons

SIGNOR-58309

O14965

Q13153

0

phosphorylation

up-regulates

0.417

The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability

SIGNOR-205110

P46934-4

P12931

0

phosphorylation

up-regulates activity

0.417

Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4.

SIGNOR-276860

Q9NRY4

P23471

0

dephosphorylation

down-regulates activity

0.417

Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP| Furthermore, Ptprz selectively dephosphorylated pY1105 of p190 RhoGAP in vitro, and the tyrosine phosphorylation at Y1105 controls p190 RhoGAP activity in vivo.

SIGNOR-248451

Q15746

P12931

0

phosphorylation

up-regulates

0.417

Ec mlck-1 is phosphorylated by p60(src) on tyr(464) and tyr(471), resulting in a 2- to 3-fold increase in ec mlck-1 enzymatic activity.

SIGNOR-85009

Q06330

Q96K30

0

binding

down-regulates

0.417

Thus, we propose that rita acts as a negative modulator of the notch signalling pathway, controlling the level of nuclear rbp-j/cbf-1, where its amounts are limiting.

SIGNOR-170089

P29320

P18031

0

dephosphorylation

down-regulates activity

0.417

Nevertheless, the finding that phosphorylation of the activation loop tyrosine (EphA3-Y779), a recently identified PTP1B substrate (Mertins et al., 2008), is essential for ligand-induced endocytosis (Janes et al., 2009)

SIGNOR-248426

P42336

P16144

0

binding

up-regulates

0.417

Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation.

SIGNOR-54530

Q92831

P78527

0

phosphorylation

up-regulates activity

0.417

In response to UV-induced DNA damage, DNA-PK phosphorylates and activates PCAF, and activated PCAF is transferred to photo lesion sites and further acetylates RPA1 at K163.

SIGNOR-280092

P04637

Q13627

0

phosphorylation

up-regulates

0.417

Dyrk1a phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. we found that dyrk1a phosphorylates p53 at ser-15 in vitro and in immortalized rat embryonic hippocampal progenitor h19-7 cells. In addition, dyrk1a-induced p53 phosphorylation at ser-15 led to a robust induction of p53 target genes

SIGNOR-167407

Q06945

Q01344

0

binding

up-regulates activity

0.417

Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation.

SIGNOR-223010

P10243

P19338

0

binding

down-regulates activity

0.417

We identify nucleolin as one of the nuclear polypeptides that interact specifically with the A-Myb and c-Myb. We show that the interaction of nucleolin with Myb is functional because co-transfection of nucleolin down-regulates Myb transcriptional activity.

SIGNOR-221233

Q9H444

Q6DKK2

0

binding

up-regulates activity

0.417

We show that PtdIns(3)P localizes to the midbody during cytokinesis and recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19, which in turn interacts with CHMP4B, an endosomal sorting complex required for transport (ESCRT)-III subunit implicated in the abscission step of cytokinesis. On the basis of these data and the high-content microscopy described above, we propose that PtdIns(3)P controls the KIF13A-dependent recruitment of FYVE-CENT and TTC19 to the midbody, and that TTC19 is the most downstream effector of the three, possibly controlling the function of CHMP4B.

SIGNOR-265541

P46940

O75122

0

binding

up-regulates activity

0.416

IQGAP1 is a novel CLASP2-interacting protein| nonphosphorylated CLASP2 on microtubules is allowed to associate with IQGAP1 for the coupling of microtubules to actin filaments at the front of migrating cells.

SIGNOR-264828

O75369

Q96Q27

0

binding

down-regulates quantity by destabilization

0.416

Here, we provide the first evidence that a novel ASB2 isoform, ASB2beta, is important for muscle differentiation. ASB2beta is expressed in muscle cells during embryogenesis and in adult tissues. ASB2beta is part of an active E3 ubiquitin ligase complex and targets the actin-binding protein filamin B (FLNb) for proteasomal degradation. Altogether, our results indicated that ASB2β can assemble with elongin B, elongin C, Cullin 5 and Rbx2 to reconstitute an active E3 ubiquitin ligase complex.ASB2β induces polyubiquitylation of FLNb.

SIGNOR-271795

Q96E17

Q86UR5

0

relocalization

up-regulates activity

0.416

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264382

Q8IU85

Q8N5S9

0

phosphorylation

up-regulates activity

0.416

CaM-KIdelta exhibits Ca(2+)/CaM-dependent activity that is enhanced (approximately 30-fold) in vitro by phosphorylation of its Thr180 by CaM-K kinase (CaM-KK)alpha, consistent with detection of CaM-KIdelta-activating activity in HeLa cells. | This sustained activation of CaM-KIdelta was completely abolished by Thr180Ala mutation and inhibited by CaM-KK inhibitor, STO-609, indicating a functional CaM-KK/CaM-KIdelta cascade in HeLa cells.

SIGNOR-250715

Q9Y6K9

P12931

0

phosphorylation

down-regulates activity

0.416

Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.

SIGNOR-276370

P53350

P60510

0

dephosphorylation

down-regulates activity

0.416

PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells.

SIGNOR-277076

Q9Y618

O15111

0

phosphorylation

down-regulates

0.416

Nf-kappab transcription requires ikkalpha to phosphorylate smrt on chromatin, stimulating the exchange of corepressor for coactivator complexes. Ikk directly phosphorylates smrt to stimulate nuclear export. Ikkalpha orchestrates smrt derepression, a prerequisite for nf-kappab transcription and survival.

SIGNOR-129956

O00329

P21860

0

binding

up-regulates

0.416

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146867

P55087

P68400

0

phosphorylation

down-regulates activity

0.416

We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.

SIGNOR-250827

P01116

P52306

0

binding

up-regulates

0.416

Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob

SIGNOR-171415

P09651

Q9UBS0

0

phosphorylation

up-regulates activity

0.416

Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export.

SIGNOR-279569

P41594

P17252

0

phosphorylation

up-regulates activity

0.416

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249278

P01148

Q9H1B7

0

transcriptional regulation

up-regulates quantity by expression

0.416

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-267154

P08254

Q9UGU0

0

transcriptional regulation

up-regulates quantity by expression

0.416

This result indicates that expression of SPBP is sufficient to transactivate a minimal promoter containing a single copy of the SPRE, as well as the full-length stromelysin promoter.

SIGNOR-266223

P27695

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.416

Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.

SIGNOR-278555

P55075

P19622

0

transcriptional regulation

down-regulates quantity by repression

0.416

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.

SIGNOR-265801

Q05193

Q13627

0

phosphorylation

down-regulates

0.416

Mnb/dyrk1a was shown to phosphorylate dynamin 1 and alter its interactions with several sh3 domain-containing endocytic accessory proteins.Phosphorylation At s795 and s857 was confirmed in full-length dynamin 1, and s857 was subsequently determined to be the major mnb/dyrk1a phosphorylation site in vitro. Phosphorylation at s857 was demonstrated to be the basis for altering the binding of dynamin 1 to amphiphysin 1 and grb 2 by site-directed mutants mimicking phosphorylation.

SIGNOR-127440

O43734

Q14164

0

phosphorylation

up-regulates activity

0.416

IKKi was required for IL-17-induced phosphorylation of Act1 on Ser311, adjacent to a putative TRAF-binding motif. Substitution of the serine at position 311 with alanine impaired the IL-17-mediated Act1-TRAF2-TRAF5 interaction and gene expression. Thus, IKKi is a kinase newly identified as modulating IL-17 signaling through its effect on Act1 phosphorylation and consequent function.

SIGNOR-262883

Q13882

P60484

0

dephosphorylation

down-regulates activity

0.416

PTEN inhibits PTK6 activity and downstream signaling in prostate cancer cells.|Using an in vitro phosphatase assay, we observed that PTEN was able to dephosphorylate PTK6 at tyrosine residue 342 in a dose dependent manner.

SIGNOR-276975

P42336

Q6ZUJ8

0

binding

up-regulates

0.416

This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Therefore, bcap is an essential activator of the pi3k pathway downstream of tlr signaling, providing a brake to limit potentially pathogenic excessive tlr responses.

SIGNOR-191664

Q16539

O00206

0

phosphorylation

up-regulates activity

0.416

Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-κB. Activation of neutrophils by S100A9 also proceeds via p38 MAPK, JNK, and ERK1/2 phosphorylation.

SIGNOR-263652

P08581

O15409

0

transcriptional regulation

down-regulates quantity by repression

0.416

FOXP2 binds directly to the 5' regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET. The expression of MET in restricted human neocortical regions, and its regulation in part by FOXP2, is consistent with genetic evidence for MET contributing to ASD risk.

SIGNOR-269054

P50542

P62837

0

ubiquitination

down-regulates quantity by destabilization

0.416

Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.

SIGNOR-253023

P00519

Q13177

0

phosphorylation

down-regulates

0.415

The interaction of c-abl with the abl interactor protein abi2 is shown to be negatively regulated by phosphorylation of serines 637 and 638. These serines are adjacent to the pxxp motif (ptppkrs637s638sfr) that binds the sh3 domain of abi. phosphorylation of c-abl by pak2 inhibits the interaction between the sh3 domain of abi2 and the pxxp motif of c-abl.

SIGNOR-160215

Q13153

Q8N1N5

0

binding

up-regulates

0.415

We further found that cripak interacted with pak1 through the n-terminal regulatory domain and inhibited pak1 kinase in both in vitro and in vivo assays.

SIGNOR-141467

P63096

Q9H1C0

0

binding

up-regulates activity

0.415

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-256718

Q9NS91

O76064

0

binding

up-regulates

0.415

Rnf8 depletion also significantly reduced the accumulation of rad18 to chromatin fraction after ir

SIGNOR-185593