GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P29350	P43405	1	dephosphorylation	down-regulates	0.737	We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene.	SIGNOR-70234
P18433	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271540
P04637	Q13535	0	phosphorylation	up-regulates quantity by stabilization	0.742	Nhibition of atr kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 protein accumulation.	SIGNOR-115134
P40925	Q86X55	0	acetylation	down-regulates activity	0.355	Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer\|Arginine methylation at R248 negatively regulates MDH1 activity\|PRMT4/CARM1 methylates MDH1 at R248 and inhibits its dimerization	SIGNOR-267639
P43378	P00533	1	dephosphorylation	down-regulates activity	0.309	Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.\|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.	SIGNOR-277130
Q2TAL8	P41252	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269406
P00533	P00367	1	phosphorylation	up-regulates activity	0.2	EGFR phosphorylates GDH1 at Y135 and contributes to GDH1 activation.\|Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis.	SIGNOR-279706
O14965	Q13158	1	phosphorylation	up-regulates	0.343	Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194	SIGNOR-176739
Q9NY61	O96017	0	phosphorylation	up-regulates quantity by stabilization	0.358	Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.\| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.	SIGNOR-264416
Q13616	P35222	1	ubiquitination	down-regulates quantity by destabilization	0.598	These results indicate that the cul1/skp1/beta-trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin.	SIGNOR-64499
O43516	Q06187	0	phosphorylation	up-regulates activity	0.542	Based on previous reports and the present data we suggest that Btk can induce WASP activation and also facilitates its subsequent inactivation through WIP phosphorylation.\|We confirmed that Btk can indeed phosphorylate Y468 of baculovirus-generated human His-tagged WIP ( xref ), but that this is more difficult to show in cell extracts where WIP would be purified along with cellular WASP ().	SIGNOR-279801
Q02750	P06493	0	phosphorylation	down-regulates	0.496	P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well	SIGNOR-36116
P17481	Q15746	1	transcriptional regulation	down-regulates quantity by repression	0.2	Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively	SIGNOR-261640
P51812	P67809	1	phosphorylation	up-regulates	0.538	We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue.	SIGNOR-182165
P50502	P34947	0	phosphorylation	up-regulates activity	0.268	An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.	SIGNOR-262877
P51955	Q9NZQ7	1	phosphorylation	up-regulates quantity by stabilization	0.2	NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen.	SIGNOR-277314
O60674	P40763	1	phosphorylation	up-regulates activity	0.818	Activation of wild type stat3: il-6 treatment causes stat3 recruitment to receptor tyrosine phosphopeptides (gp130) where it is phosphorylated on tyrosine 705 (y) by jak kinase	SIGNOR-236463
P11279	P19484	0	transcriptional regulation	up-regulates quantity by expression	0.441	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276555
Q14721	P23469	0	dephosphorylation	down-regulates activity	0.355	Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon	SIGNOR-248450
P06241	Q00535	1	phosphorylation	up-regulates activity	0.608	Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation	SIGNOR-251156
P02749	P00742	0	cleavage	down-regulates activity	0.386	In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). \|The cleavage was completely inhibited by plasmin inhibitor (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of one order of magnitude larger than that of the intact beta2GPI.	SIGNOR-266997
Q8NHE4	O15379	0	transcriptional regulation	down-regulates quantity by repression	0.2	Consistent with previous data, HDAC3 only bound to the ATP6V0E2 promoter in the presence of ALDH2.\|Taken together, our data demonstrate that in the macrophages of LDLR-KO or ALDH2 rs671 mutant, AMPK phosphorylates ALDH2 at T356, which enables its nuclear translocation. Once in the nucleus, ALDH2 binds to HDAC3 and suppresses the transcription and protein expression of ATP6V0E2.	SIGNOR-271868
P45983	P45984	1	phosphorylation	up-regulates	0.593	Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6.	SIGNOR-155205
Q12857	A8MYZ6	1	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268875
O43524	Q92574	1	transcriptional regulation	up-regulates quantity	0.448	FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1	SIGNOR-259382
P10912	Q16829	0	dephosphorylation	down-regulates	0.313	Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor.	SIGNOR-104545
Q9NP62	Q9P0U3	0	desumoylation	up-regulates activity	0.468	We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.	SIGNOR-262681
Q9H4A3	Q9UEW8	1	phosphorylation	up-regulates	0.446	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-151671
Q14790	P49768	1	cleavage	up-regulates activity	0.368	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261760
P63000	Q96P48	0	gtpase-activating protein	down-regulates activity	0.455	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-260451
P05067	P45983	0	phosphorylation	up-regulates	0.71	Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1	SIGNOR-117852
Q13418	P49841	1	phosphorylation	down-regulates activity	0.69	ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].\|ILK knockdown activates GSK-3beta.	SIGNOR-278252
Q16539	O43255	1	phosphorylation	up-regulates	0.2	We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3.	SIGNOR-149890
P03372	O96013	0	phosphorylation	up-regulates activity	0.277	Further, PAK4 phosphorylated ER\u03b1-Ser305, a phosphorylation event needed for the PAK4 activation of ER\u03b1-dependent transcription.\|Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha dependent transcription.	SIGNOR-279472
P10275	P06493	0	phosphorylation	up-regulates	0.53	At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1	SIGNOR-175692
Q13315	Q8IUQ4	1	phosphorylation	down-regulates	0.308	Disruption of the hipk2-siah-1 complex is mediated by the atm/atr pathway and involves atm/atr-dependent phosphorylation of siah-1 at ser 19.	SIGNOR-177945
Q9ULT6	Q15262	0	dephosphorylation	up-regulates activity	0.354	We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.	SIGNOR-260110
O14654	Q9UNE7	0	polyubiquitination	down-regulates quantity by destabilization	0.2	IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).	SIGNOR-277616
O95644	Q9P1W9	0	phosphorylation	up-regulates activity	0.261	In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c).	SIGNOR-276772
Q00526	P46531	1	phosphorylation	down-regulates quantity by destabilization	0.243	Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues	SIGNOR-273167
P49840	Q05655	0	phosphorylation	down-regulates	0.342	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115722
Q9Y4K3	Q07820	1	ubiquitination	up-regulates activity	0.396	TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .\|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers.	SIGNOR-278726
P12931	P78352	1	phosphorylation	up-regulates	0.565	These results indicate that psd-95 phosphorylation by src facilitates the integration of pyk2 to psd-95 signal complex, the activation of pyk2/src, as well as the subsequent tyrosine phosphorylation of nr2a, which ultimately results in the upregulation of nmda receptor function and synaptic transmission.	SIGNOR-205120
P49815	Q15418	0	phosphorylation	down-regulates	0.768	The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1	SIGNOR-128634
Q8IW41	Q15759	0	phosphorylation	up-regulates	0.619	Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.	SIGNOR-58131
P14921	P27361	0	phosphorylation	up-regulates	0.672	We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1	SIGNOR-116494
Q9UQL6	Q05655	0	phosphorylation	down-regulates activity	0.352	In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation.	SIGNOR-260875
P42224	P00533	0	phosphorylation	up-regulates	0.738	The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation	SIGNOR-235689
P28482	Q13285	1	phosphorylation	up-regulates activity	0.463	Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway.	SIGNOR-249431
P48539	P35398	0	transcriptional regulation	up-regulates quantity by expression	0.2	RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.	SIGNOR-266848
O14867	P04406	1	transcriptional regulation	up-regulates quantity	0.2	BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells.	SIGNOR-259339
O60260	Q9Y2N7	1	ubiquitination	down-regulates quantity by destabilization	0.2	Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.	SIGNOR-263089
P04637	Q00987	0	ubiquitination	down-regulates quantity by destabilization	0.968	The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.	SIGNOR-196116
P37231	P03372	0	transcriptional regulation	down-regulates quantity by repression	0.28	Our data show for the first time that eralpha binds to ppar response element and represses its transactivation	SIGNOR-140233
P49840	P17252	0	phosphorylation	down-regulates	0.345	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115714
P27361	Q8NET8	1	phosphorylation	up-regulates activity	0.2	We observed that ERK-mediated phosphorylation of TRPV3 alters its responsiveness to repeated chemical stimuli. Among several putative ERK phosphorylation sites, we identified threonine 264 in the N-terminal ankyrin repeat domain as the most critical site for the ERK-dependent modulation of TRPV3 channel activity. Of note, Thr264 is in close vicinity to a structurally and functionally important TRPV3 region comprising an atypical finger 3 and oxygen-dependent hydroxylation site. In summary, our findings indicate that Thr264 in TRPV3 is a key ERK phosphorylation site mediating EGFR-induced sensitization of the channel to stimulate signaling pathways involved in regulating skin homeostasis.	SIGNOR-273672
P17612	Q14896	1	phosphorylation	up-regulates	0.275	Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).	SIGNOR-163760
P27361	P17535	1	phosphorylation	up-regulates	0.459	Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase.	SIGNOR-196034
Q9NPF5	P12931	0	phosphorylation	down-regulates activity	0.2	C-Src phosphorylates DMAP1 at Tyr246 and disrupts Bub3/DMAP1 complex formation.	SIGNOR-279431
P01106	P53350	0	phosphorylation	up-regulates activity	0.533	Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency	SIGNOR-243522
P35222	Q13882	0	phosphorylation	down-regulates quantity	0.305	PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.\|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.	SIGNOR-278289
P68400	P49810	1	phosphorylation	up-regulates activity	0.307	In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.	SIGNOR-250934
P49841	P49815	1	phosphorylation	up-regulates activity	0.731	Gsk3 inhibits the mtor pathway by phosphorylating tsc2 in a manner dependent on ampk-priming phosphorylation.	SIGNOR-149380
Q9H1B7	Q12947	0	transcriptional regulation	up-regulates quantity by expression	0.253	FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.	SIGNOR-267152
P35813	Q13153	1	dephosphorylation	down-regulates activity	0.337	Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop.	SIGNOR-248492
P35222	Q9H1B7	0	ubiquitination	down-regulates quantity by destabilization	0.2	FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.	SIGNOR-267153
P17252	P49768	1	phosphorylation	up-regulates activity	0.264	A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.	SIGNOR-249236
Q96FA3	P32754	1	ubiquitination	down-regulates quantity by destabilization	0.2	Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.	SIGNOR-272959
Q14790	P07948	0	phosphorylation	down-regulates activity	0.311	The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis.	SIGNOR-272980
Q13557	Q9UQD0	1	phosphorylation	up-regulates activity	0.281	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275792
P49841	Q96BR1	0	phosphorylation	down-regulates activity	0.442	Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity\|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.\|The effect of SGK1 was mimicked by PKB and SGK3.	SIGNOR-249167
P55211	Q5T447	0	polyubiquitination	down-regulates activity	0.2	HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.	SIGNOR-272329
Q13571	Q96J02	0	polyubiquitination	down-regulates quantity by destabilization	0.411	Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.	SIGNOR-272721
Q13562	Q14938	0	transcriptional regulation	up-regulates quantity	0.265	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268904
P14210	O15393	0	transcriptional regulation	up-regulates quantity by expression	0.2	we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.	SIGNOR-263657
Q9UNE7	P13569	1	polyubiquitination	down-regulates quantity by destabilization	0.471	Here we show that CHIP functions with Hsc70 to sense the folded state of CFTR and targets aberrant forms for proteasomal degradation by promoting their ubiquitination.	SIGNOR-272584
Q96R06	P49841	0	phosphorylation	up-regulates	0.271	Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta	SIGNOR-159578
P06850	P10275	0	transcriptional regulation	down-regulates quantity by repression	0.305	A direct androgenic involvement in the expression of human corticotropin-releasing hormone\|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.	SIGNOR-268723
Q9Y4C1	Q16695	1	demethylation	up-regulates activity	0.2	Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.	SIGNOR-276846
P45983	O43602	1	phosphorylation	up-regulates activity	0.286	DCX phosphorylation by JNK1 is required for glioma suppression.	SIGNOR-279217
P29317	O14493	1	phosphorylation	down-regulates activity	0.477	EphA2 associates with claudin-4 via their extracellular domains. This association, in turn, leads to phosphorylation of the cytoplasmic carboxyl terminus of claudin-4 at Tyr-208. The tyrosine phosphorylation of claudin-4 attenuates association of claudin-4 with ZO-1, decreasing integration of claudin-4 into sites of cell-cell contact and enhancing paracellular permeability. These results indicate that EphA2 moderates the function of tight junctions via phosphorylation of claudin-4.	SIGNOR-262859
P08069	P46108	1	phosphorylation	down-regulates activity	0.722	On activation of the IGF-I receptor, Crk-II binds to phosphorylated tyrosine residues, especially in the juxtamembrane region. As a result of this binding, the IGF-I receptor kinase phosphorylates Tyr-221 of Crk-II, resulting in a change in intramolecular folding and binding of the SH2 domain to the phosphorylated Tyr-221, which causes rapid disassociation of the Crk-II-IGF-I receptor complex.	SIGNOR-251273
P10912	O60674	0	phosphorylation	up-regulates activity	0.766	Jak2 is then phosphorylated and, in turn, phosphorylates the GHR and the signal transducers and activators of transcription (STAT) protein.	SIGNOR-279198
O75093	O00712	0	transcriptional regulation	up-regulates quantity	0.249	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268899
P01189	P40763	0	transcriptional regulation	up-regulates quantity by expression	0.638	We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter.	SIGNOR-263497
Q9H4B4	Q16665	1	phosphorylation	down-regulates	0.348	Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation	SIGNOR-178743
O75581	P12931	0	phosphorylation	down-regulates activity	0.396	Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.\|Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation.	SIGNOR-279289
Q16204	P24941	0	phosphorylation	up-regulates	0.2	Serine 244 phosphorylation is required for h4 apoptotic function.	SIGNOR-121198
Q9H0K1	Q15078	1	phosphorylation	down-regulates	0.331	Sik2 phosphorylates p35 at ser 91, to trigger its ubiquitylation by pja2 and promote insulin secretion. _-cell knockout of sik2 leads to accumulation of p35 and impaired secretion	SIGNOR-204648
P49841	Q14103	1	phosphorylation	down-regulates activity	0.346	In kinase assays pka phosphorylated ser-87 of hnrnp d, whereas glycogen synthase kinase-3 beta (gsk-3 beta) phosphorylated ser-83, but only if ser-87 had been pre-phosphorylated by pka. Phosphorylation of ser-87 enhanced, whereas phosphorylation of ser-83 repressed, transactivation.	SIGNOR-102582
P27695	Q00535	0	phosphorylation	up-regulates activity	0.377	Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5.	SIGNOR-276337
P28482	P05412	1	phosphorylation	up-regulates activity	0.79	Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1.	SIGNOR-201943
O00712	Q02535	1	transcriptional regulation	down-regulates quantity	0.25	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268879
P18031	P00519	1	dephosphorylation	down-regulates	0.612	These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo.	SIGNOR-56815
Q16566	Q99623	1	phosphorylation	down-regulates	0.338	Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation	SIGNOR-174437
P19404	P12931	0	phosphorylation	up-regulates activity	0.322	Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.	SIGNOR-276419
P08238	P68400	0	phosphorylation	down-regulates	0.333	Although the kinase responsible for hsp90? Phosphorylation in vivo is not known, it has been reported that ck2 can phosphorylate these sites in vitro (24). Thus, we prephosphorylated recombinant hsp90? With ck2 before addition to the reaction. Remarkably, hsp90? Phosphorylation greatly reduced its ability to inhibit apaf-1 oligomerization and caspase-9 recruitment (fig. 5b). These results indicate that the phosphorylation status of hsp90? Significantly impacts its ability to inhibit apoptosome formation.	SIGNOR-179264
Q15256	Q16539	1	dephosphorylation	down-regulates	0.558	As shown, gst-ptp-sl dephosphorylated efficiently both erk2 and p38 wild typetogether, these results indicate that the defective association of the tyrosine phosphatase ptp-sl with erk2 d319n and p38 d316n mutations impairs the retention and inactivation in the cytosol of these map kinases by ptp-sl.	SIGNOR-111762
P49789	P12931	0	phosphorylation	up-regulates activity	0.466	The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.	SIGNOR-247134
P12931	Q969H4	1	phosphorylation	up-regulates activity	0.506	We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.	SIGNOR-275918

P29350

P43405

1

dephosphorylation

down-regulates

0.737

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

SIGNOR-70234

P18433

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271540

P04637

Q13535

0

phosphorylation

up-regulates quantity by stabilization

0.742

Nhibition of atr kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 protein accumulation.

SIGNOR-115134

P40925

Q86X55

0

acetylation

down-regulates activity

0.355

Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer|Arginine methylation at R248 negatively regulates MDH1 activity|PRMT4/CARM1 methylates MDH1 at R248 and inhibits its dimerization

SIGNOR-267639

P43378

P00533

1

dephosphorylation

down-regulates activity

0.309

Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.

SIGNOR-277130

Q2TAL8

P41252

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269406

P00533

P00367

1

phosphorylation

up-regulates activity

0.2

EGFR phosphorylates GDH1 at Y135 and contributes to GDH1 activation.|Mechanistically, GDH1 is activated by EGFR through phosphorylation at tyrosine 135 and, together with RSK2, enhances the cAMP response element-binding protein (CREB) activity via CaMKIV signaling, thereby promoting metastasis.

SIGNOR-279706

O14965

Q13158

1

phosphorylation

up-regulates

0.343

Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194

SIGNOR-176739

Q9NY61

O96017

0

phosphorylation

up-regulates quantity by stabilization

0.358

Three putative Chk2 phosphorylation sites (Stevens et al., 2003) are present in Che-1 at resides Ser141, Ser474, and Ser508. Thus, we performed in vitro Chk2 kinase assays utilizing the GST-Che-1 fusion peptides spanning these residues as substrates.| Taken together, these results indicate that Chk2 phosphorylates Che-1 and this phosphorylation contributes to increase Che-1 stability.

SIGNOR-264416

Q13616

P35222

1

ubiquitination

down-regulates quantity by destabilization

0.598

These results indicate that the cul1/skp1/beta-trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin.

SIGNOR-64499

O43516

Q06187

0

phosphorylation

up-regulates activity

0.542

Based on previous reports and the present data we suggest that Btk can induce WASP activation and also facilitates its subsequent inactivation through WIP phosphorylation.|We confirmed that Btk can indeed phosphorylate Y468 of baculovirus-generated human His-tagged WIP ( xref ), but that this is more difficult to show in cell extracts where WIP would be purified along with cellular WASP ().

SIGNOR-279801

Q02750

P06493

0

phosphorylation

down-regulates

0.496

P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well

SIGNOR-36116

P17481

Q15746

1

transcriptional regulation

down-regulates quantity by repression

0.2

Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively

SIGNOR-261640

P51812

P67809

1

phosphorylation

up-regulates

0.538

We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue.

SIGNOR-182165

P50502

P34947

0

phosphorylation

up-regulates activity

0.268

An in vitro screen for novel GRK substrates revealed Hsp70 interacting protein (Hip) as a substrate. GRK5, but not GRK2, bound to and stoichiometrically phosphorylated Hip in vitro. The primary binding domain of GRK5 was mapped to residues 303-319 on Hip, while the major site of phosphorylation was identified to be Ser-346. GRK5 also bound to and phosphorylated Hip on Ser-346 in cells.we found that the phosphorylation of Ser-346 was required for proper agonist-induced internalization of the chemokine receptor CXCR4.

SIGNOR-262877

P51955

Q9NZQ7

1

phosphorylation

up-regulates quantity by stabilization

0.2

NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen.

SIGNOR-277314

O60674

P40763

1

phosphorylation

up-regulates activity

0.818

Activation of wild type stat3: il-6 treatment causes stat3 recruitment to receptor tyrosine phosphopeptides (gp130) where it is phosphorylated on tyrosine 705 (y) by jak kinase

SIGNOR-236463

P11279

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.441

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276555

Q14721

P23469

0

dephosphorylation

down-regulates activity

0.355

Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon

SIGNOR-248450

P06241

Q00535

1

phosphorylation

up-regulates activity

0.608

Constitutively active Fyn phosphorylated Tyr15 of Cdk5. Fyn Facilitates Kinase Activity of Cdk5 Via Tyr15 Phosphorylation

SIGNOR-251156

P02749

P00742

0

cleavage

down-regulates activity

0.386

In the previous study, we found that factor Xa can produce the nicked form by cleaving Lys 317-Thr 318, using recombinant human domain V (r-Domain V). |The cleavage was completely inhibited by plasmin inhibitor (alpha2PI). The nicked form was demonstrated to show reduced affinity for CL with a dissociation constant of one order of magnitude larger than that of the intact beta2GPI.

SIGNOR-266997

Q8NHE4

O15379

0

transcriptional regulation

down-regulates quantity by repression

0.2

Consistent with previous data, HDAC3 only bound to the ATP6V0E2 promoter in the presence of ALDH2.|Taken together, our data demonstrate that in the macrophages of LDLR-KO or ALDH2 rs671 mutant, AMPK phosphorylates ALDH2 at T356, which enables its nuclear translocation. Once in the nucleus, ALDH2 binds to HDAC3 and suppresses the transcription and protein expression of ATP6V0E2.

SIGNOR-271868

P45983

P45984

1

phosphorylation

up-regulates

0.593

Our studies revealed a novel mechanism in which phosphorylation of jnk2 is mediated by jnk1 before phosphorylation of p53, and then p53 is directly phosphorylated by jnk2 at ser6.

SIGNOR-155205

Q12857

A8MYZ6

1

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268875

O43524

Q92574

1

transcriptional regulation

up-regulates quantity

0.448

FoxO3a binds to and transactivates the TSC1 promoter, indicating a key role for FoxO3a in regulating TSC1 expression. Together, these data demonstrate that FoxO3a regulates glycolysis downstream of Akt through transcriptional control of Tsc1

SIGNOR-259382

P10912

Q16829

0

dephosphorylation

down-regulates

0.313

Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor.

SIGNOR-104545

Q9NP62

Q9P0U3

0

desumoylation

up-regulates activity

0.468

We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.

SIGNOR-262681

Q9H4A3

Q9UEW8

1

phosphorylation

up-regulates

0.446

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-151671

Q14790

P49768

1

cleavage

up-regulates activity

0.368

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261760

P63000

Q96P48

0

gtpase-activating protein

down-regulates activity

0.455

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-260451

P05067

P45983

0

phosphorylation

up-regulates

0.71

Phosphorylation of amyloid precursor protein at threonine 668 is essential for its copper-responsive trafficking in sh-sy5y neuroblastoma cells. We found that the threonine 668 within the abetapp intracellular domain (aid or elsewhere aicd) is indeed phosphorylated by jnk1

SIGNOR-117852

Q13418

P49841

1

phosphorylation

down-regulates activity

0.69

ILK can also directly phosphorylates GSK-3\u03b2 at Ser 9, inactivate it, and lead to activation of some transcription factors [ ].|ILK knockdown activates GSK-3beta.

SIGNOR-278252

Q16539

O43255

1

phosphorylation

up-regulates

0.2

We show that siah2 is subject to phosphorylation by p38 mapk, which increases siah2-mediated degradation of phd3.

SIGNOR-149890

P03372

O96013

0

phosphorylation

up-regulates activity

0.277

Further, PAK4 phosphorylated ER\u03b1-Ser305, a phosphorylation event needed for the PAK4 activation of ER\u03b1-dependent transcription.|Further, PAK4 phosphorylated ERalpha-Ser305, a phosphorylation event needed for the PAK4 activation of ERalpha dependent transcription.

SIGNOR-279472

P10275

P06493

0

phosphorylation

up-regulates

0.53

At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1

SIGNOR-175692

Q13315

Q8IUQ4

1

phosphorylation

down-regulates

0.308

Disruption of the hipk2-siah-1 complex is mediated by the atm/atr pathway and involves atm/atr-dependent phosphorylation of siah-1 at ser 19.

SIGNOR-177945

Q9ULT6

Q15262

0

dephosphorylation

up-regulates activity

0.354

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

SIGNOR-260110

O14654

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.2

IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).

SIGNOR-277616

O95644

Q9P1W9

0

phosphorylation

up-regulates activity

0.261

In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c).

SIGNOR-276772

Q00526

P46531

1

phosphorylation

down-regulates quantity by destabilization

0.243

Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues

SIGNOR-273167

P49840

Q05655

0

phosphorylation

down-regulates

0.342

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115722

Q9Y4K3

Q07820

1

ubiquitination

up-regulates activity

0.396

TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers.

SIGNOR-278726

P12931

P78352

1

phosphorylation

up-regulates

0.565

These results indicate that psd-95 phosphorylation by src facilitates the integration of pyk2 to psd-95 signal complex, the activation of pyk2/src, as well as the subsequent tyrosine phosphorylation of nr2a, which ultimately results in the upregulation of nmda receptor function and synaptic transmission.

SIGNOR-205120

P49815

Q15418

0

phosphorylation

down-regulates

0.768

The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1

SIGNOR-128634

Q8IW41

Q15759

0

phosphorylation

up-regulates

0.619

Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site.

SIGNOR-58131

P14921

P27361

0

phosphorylation

up-regulates

0.672

We found that hgf/sf activates the erk1 map kinase, leading to the phosphorylation of the threonine 38 residue of ets1

SIGNOR-116494

Q9UQL6

Q05655

0

phosphorylation

down-regulates activity

0.352

In this report, we show that VEGF stimulates PKD-dependent phosphorylation of HDAC5 at Ser259/498residues in ECs, which leads to HDAC5 nuclear exclusion and myocyte enhancer factor-2 (MEF2) transcriptional activation.

SIGNOR-260875

P42224

P00533

0

phosphorylation

up-regulates

0.738

The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation

SIGNOR-235689

P28482

Q13285

1

phosphorylation

up-regulates activity

0.463

Here we show that maximal SF-1-mediated transcription and interaction with general nuclear receptor cofactors depends on phosphorylation of a single serine residue (Ser-203) located in a major activation domain (AF-1) of the protein. Moreover, phosphorylation-dependent SF-1 activation is likely mediated by the mitogen-activated protein kinase (MAPK) signaling pathway.

SIGNOR-249431

P48539

P35398

0

transcriptional regulation

up-regulates quantity by expression

0.2

RORα regulates the expression of several genes in Purkinje cells. RORα becomes highly expressed in postmitotic Purkinje cells. It regulates their maturation, particularly dendritic differentiation. Dendritogenesis and the expression of several genes, including Shh, Itpr1, Pcp4, Calb1, Pcp2, and Slc1a6, normally expressed in mature Purkinje cells, are inhibited in RORα-deficient mice.

SIGNOR-266848

O14867

P04406

1

transcriptional regulation

up-regulates quantity

0.2

BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells.

SIGNOR-259339

O60260

Q9Y2N7

1

ubiquitination

down-regulates quantity by destabilization

0.2

Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.

SIGNOR-263089

P04637

Q00987

0

ubiquitination

down-regulates quantity by destabilization

0.968

The E3 ubiquitin ligase, MDM2, uses a dual-site mechanism to ubiquitinate and degrade the tumor suppressor protein p53, involving interactions with the N-terminal hydrophobic pocket and the acidic domain of MDM2.

SIGNOR-196116

P37231

P03372

0

transcriptional regulation

down-regulates quantity by repression

0.28

Our data show for the first time that eralpha binds to ppar response element and represses its transactivation

SIGNOR-140233

P49840

P17252

0

phosphorylation

down-regulates

0.345

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115714

P27361

Q8NET8

1

phosphorylation

up-regulates activity

0.2

We observed that ERK-mediated phosphorylation of TRPV3 alters its responsiveness to repeated chemical stimuli. Among several putative ERK phosphorylation sites, we identified threonine 264 in the N-terminal ankyrin repeat domain as the most critical site for the ERK-dependent modulation of TRPV3 channel activity. Of note, Thr264 is in close vicinity to a structurally and functionally important TRPV3 region comprising an atypical finger 3 and oxygen-dependent hydroxylation site. In summary, our findings indicate that Thr264 in TRPV3 is a key ERK phosphorylation site mediating EGFR-induced sensitization of the channel to stimulate signaling pathways involved in regulating skin homeostasis.

SIGNOR-273672

P17612

Q14896

1

phosphorylation

up-regulates

0.275

Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).

SIGNOR-163760

P27361

P17535

1

phosphorylation

up-regulates

0.459

Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase.

SIGNOR-196034

Q9NPF5

P12931

0

phosphorylation

down-regulates activity

0.2

C-Src phosphorylates DMAP1 at Tyr246 and disrupts Bub3/DMAP1 complex formation.

SIGNOR-279431

P01106

P53350

0

phosphorylation

up-regulates activity

0.533

Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency

SIGNOR-243522

P35222

Q13882

0

phosphorylation

down-regulates quantity

0.305

PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.

SIGNOR-278289

P68400

P49810

1

phosphorylation

up-regulates activity

0.307

In vitro the large hydrophilic loop of PS-2 between transmembrane domains 6 and 7 can be phosphorylated by casein kinase-1 (CK-1) and CK-2, but not by PKA or PKC. Quantitative analysis of in vitro phosphorylation demonstrates the presence of two phosphorylation sites for CK-1 and a single site for CK-2. A deletion analysis revealed that the CTF of PS-2 is phosphorylated in vivo within an acidic sequence containing three potential phosphorylation sites for CKs (serines 327, 330, and 335). These data suggest that CK type protein kinases phosphorylate the CTF of PS-2 within its hydrophilic loop domain in vivo. Interestingly, the potential phosphorylation sites are located directly adjacent to the recently identified caspase cleavage sites.

SIGNOR-250934

P49841

P49815

1

phosphorylation

up-regulates activity

0.731

Gsk3 inhibits the mtor pathway by phosphorylating tsc2 in a manner dependent on ampk-priming phosphorylation.

SIGNOR-149380

Q9H1B7

Q12947

0

transcriptional regulation

up-regulates quantity by expression

0.253

FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.

SIGNOR-267152

P35813

Q13153

1

dephosphorylation

down-regulates activity

0.337

Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop.

SIGNOR-248492

P35222

Q9H1B7

0

ubiquitination

down-regulates quantity by destabilization

0.2

FOXF2 directly bound the promoter of E3 ligase interferon regulatory factor 2-binding protein-like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn interacted with β-catenin, increasing its ubiquitination and degradation.

SIGNOR-267153

P17252

P49768

1

phosphorylation

up-regulates activity

0.264

A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis.

SIGNOR-249236

Q96FA3

P32754

1

ubiquitination

down-regulates quantity by destabilization

0.2

Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.

SIGNOR-272959

Q14790

P07948

0

phosphorylation

down-regulates activity

0.311

The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis.

SIGNOR-272980

Q13557

Q9UQD0

1

phosphorylation

up-regulates activity

0.281

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275792

P49841

Q96BR1

0

phosphorylation

down-regulates activity

0.442

Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.|The effect of SGK1 was mimicked by PKB and SGK3.

SIGNOR-249167

P55211

Q5T447

0

polyubiquitination

down-regulates activity

0.2

HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.

SIGNOR-272329

Q13571

Q96J02

0

polyubiquitination

down-regulates quantity by destabilization

0.411

Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.

SIGNOR-272721

Q13562

Q14938

0

transcriptional regulation

up-regulates quantity

0.265

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

SIGNOR-268904

P14210

O15393

0

transcriptional regulation

up-regulates quantity by expression

0.2

we identified pro-hepatocyte growth factor (HGF) as a TMPRSS2 substrate and confirmed that HGF and it’s cognate receptor c-Met are activated in prostate cancers expressing TMPRSS2, a finding that also associated with the acquisition of a pro-invasive mesenchymal gene expression program.

SIGNOR-263657

Q9UNE7

P13569

1

polyubiquitination

down-regulates quantity by destabilization

0.471

Here we show that CHIP functions with Hsc70 to sense the folded state of CFTR and targets aberrant forms for proteasomal degradation by promoting their ubiquitination.

SIGNOR-272584

Q96R06

P49841

0

phosphorylation

up-regulates

0.271

Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta

SIGNOR-159578

P06850

P10275

0

transcriptional regulation

down-regulates quantity by repression

0.305

A direct androgenic involvement in the expression of human corticotropin-releasing hormone|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.

SIGNOR-268723

Q9Y4C1

Q16695

1

demethylation

up-regulates activity

0.2

Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.

SIGNOR-276846

P45983

O43602

1

phosphorylation

up-regulates activity

0.286

DCX phosphorylation by JNK1 is required for glioma suppression.

SIGNOR-279217

P29317

O14493

1

phosphorylation

down-regulates activity

0.477

EphA2 associates with claudin-4 via their extracellular domains. This association, in turn, leads to phosphorylation of the cytoplasmic carboxyl terminus of claudin-4 at Tyr-208. The tyrosine phosphorylation of claudin-4 attenuates association of claudin-4 with ZO-1, decreasing integration of claudin-4 into sites of cell-cell contact and enhancing paracellular permeability. These results indicate that EphA2 moderates the function of tight junctions via phosphorylation of claudin-4.

SIGNOR-262859

P08069

P46108

1

phosphorylation

down-regulates activity

0.722

On activation of the IGF-I receptor, Crk-II binds to phosphorylated tyrosine residues, especially in the juxtamembrane region. As a result of this binding, the IGF-I receptor kinase phosphorylates Tyr-221 of Crk-II, resulting in a change in intramolecular folding and binding of the SH2 domain to the phosphorylated Tyr-221, which causes rapid disassociation of the Crk-II-IGF-I receptor complex.

SIGNOR-251273

P10912

O60674

0

phosphorylation

up-regulates activity

0.766

Jak2 is then phosphorylated and, in turn, phosphorylates the GHR and the signal transducers and activators of transcription (STAT) protein.

SIGNOR-279198

O75093

O00712

0

transcriptional regulation

up-regulates quantity

0.249

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

SIGNOR-268899

P01189

P40763

0

transcriptional regulation

up-regulates quantity by expression

0.638

We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter.

SIGNOR-263497

Q9H4B4

Q16665

1

phosphorylation

down-regulates

0.348

Polo-like kinase 3 functions as a tumor suppressor and is a negative regulator of hypoxia-inducible factor-1 alpha under hypoxic conditionsplk3 can potentially inhibit hif-1_ by physical interaction and direct phosphorylation

SIGNOR-178743

O75581

P12931

0

phosphorylation

down-regulates activity

0.396

Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.|Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation.

SIGNOR-279289

Q16204

P24941

0

phosphorylation

up-regulates

0.2

Serine 244 phosphorylation is required for h4 apoptotic function.

SIGNOR-121198

Q9H0K1

Q15078

1

phosphorylation

down-regulates

0.331

Sik2 phosphorylates p35 at ser 91, to trigger its ubiquitylation by pja2 and promote insulin secretion. _-cell knockout of sik2 leads to accumulation of p35 and impaired secretion

SIGNOR-204648

P49841

Q14103

1

phosphorylation

down-regulates activity

0.346

In kinase assays pka phosphorylated ser-87 of hnrnp d, whereas glycogen synthase kinase-3 beta (gsk-3 beta) phosphorylated ser-83, but only if ser-87 had been pre-phosphorylated by pka. Phosphorylation of ser-87 enhanced, whereas phosphorylation of ser-83 repressed, transactivation.

SIGNOR-102582

P27695

Q00535

0

phosphorylation

up-regulates activity

0.377

Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5.

SIGNOR-276337

P28482

P05412

1

phosphorylation

up-regulates activity

0.79

Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1.

SIGNOR-201943

O00712

Q02535

1

transcriptional regulation

down-regulates quantity

0.25

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

SIGNOR-268879

P18031

P00519

1

dephosphorylation

down-regulates

0.612

These results illustrate selectivity in the effects of ptps in a cellular context and suggest that ptp1b may function as a specific, negative regulator of p210 bcr-abl signalling in vivo.

SIGNOR-56815

Q16566

Q99623

1

phosphorylation

down-regulates

0.338

Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation

SIGNOR-174437

P19404

P12931

0

phosphorylation

up-regulates activity

0.322

Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.

SIGNOR-276419

P08238

P68400

0

phosphorylation

down-regulates

0.333

Although the kinase responsible for hsp90? Phosphorylation in vivo is not known, it has been reported that ck2 can phosphorylate these sites in vitro (24). Thus, we prephosphorylated recombinant hsp90? With ck2 before addition to the reaction. Remarkably, hsp90? Phosphorylation greatly reduced its ability to inhibit apaf-1 oligomerization and caspase-9 recruitment (fig. 5b). These results indicate that the phosphorylation status of hsp90? Significantly impacts its ability to inhibit apoptosome formation.

SIGNOR-179264

Q15256

Q16539

1

dephosphorylation

down-regulates

0.558

As shown, gst-ptp-sl dephosphorylated efficiently both erk2 and p38 wild typetogether, these results indicate that the defective association of the tyrosine phosphatase ptp-sl with erk2 d319n and p38 d316n mutations impairs the retention and inactivation in the cytosol of these map kinases by ptp-sl.

SIGNOR-111762

P49789

P12931

0

phosphorylation

up-regulates activity

0.466

The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.

SIGNOR-247134

P12931

Q969H4

1

phosphorylation

up-regulates activity

0.506

We identified Tyr 26 as a PDGF-induced and, additionally, Tyr 519 and Tyr 665 as SRC-induced tyrosine phosphorylation sites. Phosphomimetic mutants indicate that phosphorylation of Tyr 519 recruits CNK1 to the nucleus and additional phosphorylation of Tyr 26 enables CNK1 to promote SRE-dependent gene expression.

SIGNOR-275918