GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P55011	O95747	0	phosphorylation	up-regulates	0.524	The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.	SIGNOR-90927
O60260	P42345	0	phosphorylation	down-regulates activity	0.2	MTOR phosphorylates PARK2 at Ser127 Through biochemical, mutational, and genetic studies, we identified PARK2 as a mTORC1 substrate. mTORC1 phosphorylates PARK2 at Ser127, which blocks its cellular ubiquitination activity, thereby hindering its tumor suppressor effect on eIF4B's stability.	SIGNOR-277586
P23458	P35568	1	phosphorylation	up-regulates activity	0.708	Janus kinase-dependent activation of insulin receptor substrate 1	SIGNOR-251343
P05771	Q12906	1	phosphorylation	up-regulates activity	0.2	Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.\|Our results support a model in which PMA stimulation activates PKCβI to phosphorylate NF90-Ser647, and this phosphorylation triggers NF90 relocation to the cytoplasm and stabilize IL-2 mRNA.	SIGNOR-168173
O15264	O00418	1	phosphorylation	down-regulates activity	0.578	eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]	SIGNOR-250089
Q01668	P17612	0	phosphorylation	up-regulates activity	0.396	We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.	SIGNOR-263109
P16591	P40763	1	phosphorylation	up-regulates activity	0.402	Replacing the unique 43-amino acid-long N-terminal tail of p51 (ferT) with a parallel segment from the N-terminal tail of p94 (fer) did not change the subcellular localization of p51 (ferT) but enabled it to activate Stat3.\|When combined with immunoprecipitation analysis, this assay showed that p94 (fer) can lead to the tyrosine phosphorylation and activation of Stat3 but not of Stat1 or Stat2.	SIGNOR-279713
P41594	Q05655	0	phosphorylation	up-regulates activity	0.348	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-249287
Q14457	Q13464	0	phosphorylation	up-regulates activity	0.415	Beclin1 is phosphorylated by ROCK1 at T119.	SIGNOR-278198
O14920	Q9Y4G8	1	phosphorylation	down-regulates quantity by destabilization	0.2	Taken together, these results indicate that IKK\u03b2-dependent phosphorylation of RAPGEF2 is required for RAPGEF2 degradation induced by HGF and mediated by \u03b2TrCP.	SIGNOR-279807
Q14847	P00519	0	phosphorylation	up-regulates	0.343	C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins.	SIGNOR-124719
Q8TD94	Q9NYA1	1	transcriptional regulation	up-regulates quantity by expression	0.2	KLF14 Is a Transcriptional Activator of SK1 Gene Expression in Endothelial Cells	SIGNOR-266047
Q8NEL9	P67775	0	dephosphorylation	up-regulates activity	0.2	Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity	SIGNOR-262975
Q8WXD5	P35637	0	relocalization	up-regulates activity	0.2	Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.\|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 \|Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells	SIGNOR-262106
P55211	Q02750	0	phosphorylation	down-regulates activity	0.439	Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK\|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2	SIGNOR-249385
Q15418	P23588	1	phosphorylation	up-regulates	0.529	S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function.	SIGNOR-123993
P49137	Q9UPN4	1	phosphorylation	down-regulates quantity	0.291	We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.\|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.	SIGNOR-278181
P12931	P04637	1	phosphorylation	down-regulates quantity by destabilization	0.524	We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.	SIGNOR-276668
Q02548	P43405	0	phosphorylation	down-regulates activity	0.422	PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.	SIGNOR-269084
Q00526	P03372	1	phosphorylation	up-regulates activity	0.259	CDK3 was shown to be overexpressed in breast cancer and phosphorylate ERα at Ser104/116 and Ser118. Furthermore, we found that Mir-873 inhibits ER activity and cell growth via targeting CDK3	SIGNOR-273187
P06241	Q15858	1	phosphorylation	up-regulates activity	0.363	Our results demonstrate Fyn -mediated upregulation of Nav1.7 protein expression and tyrosine phosphorylation and identify two tyrosine residues within the DIII-DIV linker (L3) as Fyn phosphorylation sites.	SIGNOR-279614
P06493	P08047	1	phosphorylation	up-regulates	0.463	Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis.	SIGNOR-163738
O60506	P11362	0	phosphorylation	down-regulates	0.2	Novel in vivo tyrosine phosphorylation sites were found in the fgfr-1, phospholipase cgamma, p90 ribosomal s6 kinase, cortactin, and ns-1-associated protein-1. Syncrip, was very recently found to be phosphorylated in response to insulin treatment of 3t3-l1 adipocytes (32). Phosphorylation of syncrip was accommodated by the insulin receptor tyrosine kinase in vitro but was inhibited upon binding of rna. Tyrosine phosphorylation at tyr-373 in the third rna recognition motif domain of nsap1/syncrip can possibly influence its rna binding properties and thus link fgfr-1 signaling to mrna metabolism.	SIGNOR-98704
P14618	P30304	0	dephosphorylation	up-regulates activity	0.487	Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.\|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.	SIGNOR-276967
O15519	P17252	0	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276147
Q5JU85	P62330	1	guanine nucleotide exchange factor	up-regulates activity	0.457	Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.	SIGNOR-264906
Q16539	P61244	1	phosphorylation	down-regulates	0.627	Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression.	SIGNOR-26511
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
P42575	P36873	0	dephosphorylation	up-regulates activity	0.2	nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.	SIGNOR-248503
Q96SN8	O43379	1	relocalization	up-regulates activity	0.545	Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.	SIGNOR-271723
Q15788	P04150	0	transcriptional regulation	up-regulates quantity by expression	0.769	Transactivation of these templates depends on the association of the GR with co-activators such as SRC-1/NcoA1, GRIP-1/TIF-2/NcoA2 and p300/CBP.	SIGNOR-251682
Q15139	Q8NEB9	1	phosphorylation	up-regulates activity	0.371	PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.\|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.	SIGNOR-278495
Q13315	Q9H3D4	1	phosphorylation	down-regulates	0.403	Atm kinase is a master switch for the delta np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon dna damage. We previously found that the pro-apoptotic dna damaging agent, cisplatin, mediated the proteasome-dependent degradation of delta np63 alpha associated with its increased phosphorylated status. We found that delta np63 alpha is phosphorylated in the time-dependent fashion at the following positions: s385, t397 and s466, which were surrounded by recognition motifs for atm, cdk2 and p70s6k kinases, respectively	SIGNOR-180747
P17096	Q9H2X6	0	phosphorylation	down-regulates	0.493	Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.	SIGNOR-158620
Q9UKV8	O00743	0	dephosphorylation	up-regulates activity	0.328	Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.	SIGNOR-276515
Q13950	Q8IYA7	0	transcriptional regulation	up-regulates quantity by expression	0.301	MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).	SIGNOR-267215
O60563	Q92585	0	relocalization	up-regulates	0.2	Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells.	SIGNOR-130712
P00533	Q9BV68	0	polyubiquitination	down-regulates quantity by destabilization	0.328	RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.	SIGNOR-272103
Q6ZNA4	P29590	1	polyubiquitination	down-regulates quantity by destabilization	0.355	Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.	SIGNOR-272883
P31749	Q13107	1	phosphorylation	up-regulates quantity by stabilization	0.465	AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.	SIGNOR-273482
P51955	Q5T7B8	1	phosphorylation	up-regulates activity	0.695	Nek2 binds and phosphorylates Kif24.\|We also provide evidence that Nek2 dependent phosphorylation induces a conformational change in Kif24 that promotes its activity.	SIGNOR-278413
Q8N163	P19784	0	phosphorylation	up-regulates activity	0.2	CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. \|In our results, CK2alpha affected the\|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1	SIGNOR-267667
Q92793	O75177	0	relocalization	up-regulates	0.397	The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.	SIGNOR-129926
P01574	P03209	0	transcriptional regulation	down-regulates quantity by repression	0.2	Epstein-Barr Virus BRLF1 Inhibits Transcription of IRF3 and IRF7 and Suppresses Induction of Interferon-β. These results suggest that EBV Rta is capable of regulating the activation of the IFN-β promoter.	SIGNOR-266646
P45983	Q96KB5	0	phosphorylation	up-regulates activity	0.303	Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.\|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.	SIGNOR-280061
Q96RT7	O00444	0	phosphorylation	up-regulates activity	0.701	Plk4 interacts with and phosphorylates GCP6. we show that GCP6 is an integral component of the centriole and required for centriole duplication. Moreover, we find that GCP6 interacts in vitro and in vivo with Plk4. We show that phosphorylation of GCP6 by Plk4 is required for Plk4-induced centriole overduplication.	SIGNOR-262902
Q8IW41	Q16539	0	phosphorylation	up-regulates activity	0.637	In hela cells, prak was activated in response to cellular stress and proinflammatory cytokines. 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-58135
Q13535	P04637	1	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
P05198	Q9UI10	0	guanine nucleotide exchange factor	up-regulates activity	0.869	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269127
P35221	Q06124	0	dephosphorylation	down-regulates	0.435	Tyr148 of beta-catenin is an shp2 target dephosphorylation site. Together, these results suggest that beta-catenin plays a suppressor role in cell transformation and that shp2, by dephosphorylating beta-catenin, promotes mitogenic, cell survival and transformation signals.	SIGNOR-147075
Q05397	P09619	0	phosphorylation	up-regulates	0.553	In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases.	SIGNOR-167658
P05129	P49768	1	phosphorylation	up-regulates activity	0.2	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-249238
P55085	P08311	0	cleavage	down-regulates activity	0.526	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263585
Q9H4A3	Q9Y3S1	0	phosphorylation	up-regulates activity	0.546	WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). \| We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.	SIGNOR-260790
Q86Y01	Q96J02	0	ubiquitination	down-regulates	0.7	Itch/aip4 mediates deltex degradation through the formation of k29-linked polyubiquitin chains.	SIGNOR-150002
P35579	P35222	1	transcriptional regulation	up-regulates quantity by expression	0.274	Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo.	SIGNOR-278896
Q16654	P11498	1	phosphorylation	down-regulates activity	0.373	PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.	SIGNOR-278974
Q13115	P45984	1	dephosphorylation	down-regulates	0.606	We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. . Mkp-2 had detectable activity against jnk2, although full inactivation of jnk2 was not observed even at the higher phosphatase concentration.	SIGNOR-40929
Q13363	Q13131	0	phosphorylation	down-regulates	0.2	We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1	SIGNOR-200250
P28482	P24941	1	phosphorylation	up-regulates	0.497	In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.	SIGNOR-94003
Q13501	Q14145	1	ubiquitination	down-regulates quantity by destabilization	0.712	When autophagy is impaired, accumulated SQSTM1 interacts with KEAP1, leading to the proteasomal degradation of KEAP1. This interaction sequesters KEAP1 away from NFE2L2, preventing the ubiquitination and degradation of NFE2L2. Consequently, NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins.	SIGNOR-279849
Q8N103	P63000	1	gtpase-activating protein	down-regulates activity	0.402	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-260524
P46019	P22612	0	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267414
P49356	P01112	1	null	up-regulates activity	0.46	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-242565
O14965	P35222	1	phosphorylation	up-regulates quantity	0.346	In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic \u03b2-catenin expression in esophageal squamous cell carcinoma tissues.\|We also demonstrate for the first time that Aurora-A directly interacts with \u03b2-catenin and phosphorylates \u03b2-catenin at Ser552 and Ser675.	SIGNOR-278468
Q9HC98	Q9HC35	1	phosphorylation	up-regulates activity	0.253	The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.	SIGNOR-273883
Q13153	Q14247	1	phosphorylation	up-regulates	0.707	Strikingly, we find that pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with n-wasp. Thus, pak1, by controlling the interaction between cortactin and n-wasp, could regulate the polymerization of actin during clathrin-independent endocytosis.	SIGNOR-169690
P49841	P11308	1	phosphorylation	down-regulates quantity by destabilization	0.2	Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively.	SIGNOR-277528
P63000	Q9Y3L3	0	gtpase-activating protein	down-regulates activity	0.38	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-260514
Q9UBK2	P31749	0	phosphorylation	down-regulates activity	0.447	Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1alpha At ser570 Is required for akt to inhibit recruitment of pgc-1alpha To chromatin.	SIGNOR-252502
Q96QP1	Q96CG3	1	phosphorylation	up-regulates activity	0.247	The authors proposed that binding of ADP-Hep caused a conformational change exposing the catalytic cleft and allowing for ALPK1 to phosphorylate and activate TIFA leading to downstream NF-kB activation.	SIGNOR-279789
P06239	Q13444	1	phosphorylation	up-regulates	0.349	Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.	SIGNOR-112931
P17252	P35367	1	phosphorylation	down-regulates	0.2	In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r.	SIGNOR-66015
P12931	Q16595	1	phosphorylation	down-regulates quantity by destabilization	0.2	We found that frataxin can be phosphorylated by Src. Phosphorylation occurs primarily on Y118 and promotes frataxin ubiquitination, a signal for degradation.	SIGNOR-275585
P46937	Q14164	0	phosphorylation	down-regulates quantity by destabilization	0.44	Virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response.	SIGNOR-277355
O15111	Q04206	1	phosphorylation	up-regulates activity	0.847	Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.	SIGNOR-129931
P52565	P17252	0	phosphorylation	down-regulates activity	0.449	PKCalpha phosphorylates RhoGDIalpha at Ser34 to reduce its affinity for RhoA (but not for Rac1 or Cdc42) .	SIGNOR-279097
P36507	P28482	1	phosphorylation	up-regulates	0.744	Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.	SIGNOR-86709
P49336	P68431	1	phosphorylation	down-regulates activity	0.2	However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.	SIGNOR-273171
P12931	O75581	1	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
P67809	P51812	0	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
Q14258	Q7Z434	1	polyubiquitination	down-regulates quantity by destabilization	0.77	We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.	SIGNOR-272042
P01106	P45984	0	phosphorylation	up-regulates	0.359	The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.	SIGNOR-72108
O00308	P24928	1	ubiquitination	down-regulates quantity	0.387	WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks\|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.	SIGNOR-268851
P31749	P38936	1	phosphorylation	up-regulates quantity by stabilization	0.84	Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival.	SIGNOR-157790
P16885	P07333	0	null	up-regulates	0.369	Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway	SIGNOR-255570
O96017	P54132	1	phosphorylation	down-regulates quantity by destabilization	0.526	We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges.	SIGNOR-276908
P53350	P54274	1	phosphorylation	up-regulates	0.373	Plk1 phosphorylation of trf1 is essential for its binding to telomeres	SIGNOR-179461
Q13164	Q06413	1	phosphorylation	up-regulates	0.766	Bmk1 dramatically enhances the transactivation activity of mef2c by phosphorylating a serine residue at amino acid position 387 in this transcription factor.	SIGNOR-53545
Q92900	Q9Y243	0	phosphorylation	up-regulates activity	0.2	AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity	SIGNOR-277596
Q13835	P31751	0	phosphorylation	up-regulates quantity by stabilization	0.267	Akt2 phosphorylates PKP1 in vitro. Phosphorylated PKP1 is more resistant to degradation. PKP1 phosphorylation sites identified by peptide microarray analyses and mass spectrometry.	SIGNOR-273494
Q15796	Q9H4A3	0	phosphorylation	up-regulates quantity	0.2	In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.	SIGNOR-280164
P13349	P68400	0	phosphorylation	up-regulates activity	0.307	Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.	SIGNOR-250922
P10415	P45983	0	phosphorylation	down-regulates	0.582	G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..	SIGNOR-72361
P42261	Q13237	0	phosphorylation	up-regulates activity	0.44	In cultured hippocampal neurons, activation of cGKII induces an accumulation of GluR1 on the cellular plasma membrane at extrasynaptic sites, and blockage of cGKII activity prevents the surface increase of GluR1, and also the increase in mEPSC frequency and amplitude, that follows a chemical form of LTP (chemLTP).\|In this complex, cGKII phosphorylates GluR1 at serine 845 (S845), a site known to be phosphorylated also by PKA.	SIGNOR-278427
Q9C0H9	P12931	0	phosphorylation	up-regulates activity	0.496	Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.	SIGNOR-263196
Q7LBC6	Q07869	1	transcriptional regulation	up-regulates quantity by expression	0.2	We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression.	SIGNOR-266637
P68104	P05771	0	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263167
P27361	Q8IZP0	1	phosphorylation	up-regulates	0.454	We show that erk colocalizes with the wrc at lamellipodial leading edges and directly phosphorylates two wrc components: wave2 and abi1.	SIGNOR-172881
P31749	P55265	1	phosphorylation	down-regulates activity	0.281	AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively	SIGNOR-276193

P55011

O95747

0

phosphorylation

up-regulates

0.524

The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.

SIGNOR-90927

O60260

P42345

0

phosphorylation

down-regulates activity

0.2

MTOR phosphorylates PARK2 at Ser127 Through biochemical, mutational, and genetic studies, we identified PARK2 as a mTORC1 substrate. mTORC1 phosphorylates PARK2 at Ser127, which blocks its cellular ubiquitination activity, thereby hindering its tumor suppressor effect on eIF4B's stability.

SIGNOR-277586

P23458

P35568

1

phosphorylation

up-regulates activity

0.708

Janus kinase-dependent activation of insulin receptor substrate 1

SIGNOR-251343

P05771

Q12906

1

phosphorylation

up-regulates activity

0.2

Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our results support a model in which PMA stimulation activates PKCβI to phosphorylate NF90-Ser647, and this phosphorylation triggers NF90 relocation to the cytoplasm and stabilize IL-2 mRNA.

SIGNOR-168173

O15264

O00418

1

phosphorylation

down-regulates activity

0.578

eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]

SIGNOR-250089

Q01668

P17612

0

phosphorylation

up-regulates activity

0.396

We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.

SIGNOR-263109

P16591

P40763

1

phosphorylation

up-regulates activity

0.402

Replacing the unique 43-amino acid-long N-terminal tail of p51 (ferT) with a parallel segment from the N-terminal tail of p94 (fer) did not change the subcellular localization of p51 (ferT) but enabled it to activate Stat3.|When combined with immunoprecipitation analysis, this assay showed that p94 (fer) can lead to the tyrosine phosphorylation and activation of Stat3 but not of Stat1 or Stat2.

SIGNOR-279713

P41594

Q05655

0

phosphorylation

up-regulates activity

0.348

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-249287

Q14457

Q13464

0

phosphorylation

up-regulates activity

0.415

Beclin1 is phosphorylated by ROCK1 at T119.

SIGNOR-278198

O14920

Q9Y4G8

1

phosphorylation

down-regulates quantity by destabilization

0.2

Taken together, these results indicate that IKK\u03b2-dependent phosphorylation of RAPGEF2 is required for RAPGEF2 degradation induced by HGF and mediated by \u03b2TrCP.

SIGNOR-279807

Q14847

P00519

0

phosphorylation

up-regulates

0.343

C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins.

SIGNOR-124719

Q8TD94

Q9NYA1

1

transcriptional regulation

up-regulates quantity by expression

0.2

KLF14 Is a Transcriptional Activator of SK1 Gene Expression in Endothelial Cells

SIGNOR-266047

Q8NEL9

P67775

0

dephosphorylation

up-regulates activity

0.2

Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity

SIGNOR-262975

Q8WXD5

P35637

0

relocalization

up-regulates activity

0.2

Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells

SIGNOR-262106

P55211

Q02750

0

phosphorylation

down-regulates activity

0.439

Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2

SIGNOR-249385

Q15418

P23588

1

phosphorylation

up-regulates

0.529

S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function.

SIGNOR-123993

P49137

Q9UPN4

1

phosphorylation

down-regulates quantity

0.291

We identify CEP131 as a major Centriolar satellites-associated substrate of p38-dependent, MK2-mediated phosphorylation on two defined residues and show that these modifications promote binding to 14-3-3 proteins, in turn leading to cytoplasmic sequestration of CEP131 and associated Centriolar satellites factors.|We therefore conclude that MK2 dependent phosphorylation of CEP131 at S47 and S78 and the ensuing binding of 14-3-3 proteins play an essential role in triggering stress induced remodelling of CS.

SIGNOR-278181

P12931

P04637

1

phosphorylation

down-regulates quantity by destabilization

0.524

We recently found that ISGylation of the p53 tumor suppressor is an important novel mechanism to control its stability. Here we identified that Isg15-dependent regulation of p53 can be enhanced by different oncogenes. We further show that the Src-mediated phosphorylation of p53 on Tyr126 and Tyr220 has a positive effect on p53 ISGylation by enhancing Herc5 binding.

SIGNOR-276668

Q02548

P43405

0

phosphorylation

down-regulates activity

0.422

PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation.

SIGNOR-269084

Q00526

P03372

1

phosphorylation

up-regulates activity

0.259

CDK3 was shown to be overexpressed in breast cancer and phosphorylate ERα at Ser104/116 and Ser118. Furthermore, we found that Mir-873 inhibits ER activity and cell growth via targeting CDK3

SIGNOR-273187

P06241

Q15858

1

phosphorylation

up-regulates activity

0.363

Our results demonstrate Fyn -mediated upregulation of Nav1.7 protein expression and tyrosine phosphorylation and identify two tyrosine residues within the DIII-DIV linker (L3) as Fyn phosphorylation sites.

SIGNOR-279614

P06493

P08047

1

phosphorylation

up-regulates

0.463

Moreover, we showed that sp1 is a novel mitotic substrate of cdk1/cyclin b1 and is phosphorylated by it at thr 739 before the onset of mitosis.

SIGNOR-163738

O60506

P11362

0

phosphorylation

down-regulates

0.2

Novel in vivo tyrosine phosphorylation sites were found in the fgfr-1, phospholipase cgamma, p90 ribosomal s6 kinase, cortactin, and ns-1-associated protein-1. Syncrip, was very recently found to be phosphorylated in response to insulin treatment of 3t3-l1 adipocytes (32). Phosphorylation of syncrip was accommodated by the insulin receptor tyrosine kinase in vitro but was inhibited upon binding of rna. Tyrosine phosphorylation at tyr-373 in the third rna recognition motif domain of nsap1/syncrip can possibly influence its rna binding properties and thus link fgfr-1 signaling to mrna metabolism.

SIGNOR-98704

P14618

P30304

0

dephosphorylation

up-regulates activity

0.487

Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.

SIGNOR-276967

O15519

P17252

0

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276147

Q5JU85

P62330

1

guanine nucleotide exchange factor

up-regulates activity

0.457

Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.

SIGNOR-264906

Q16539

P61244

1

phosphorylation

down-regulates

0.627

Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression.

SIGNOR-26511

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

P42575

P36873

0

dephosphorylation

up-regulates activity

0.2

nutrient-replete oocytes inhibit C2 via S135 phosphorylation catalyzed by calcium/calmodulin-dependent protein kinase II. We now show that C2 phosphorylated at S135 binds 14-3-3zeta, thus preventing C2 dephosphorylation. Moreover, we determined that S135 dephosphorylation is catalyzed by protein phosphatase-1 (PP1), which directly binds C2.

SIGNOR-248503

Q96SN8

O43379

1

relocalization

up-regulates activity

0.545

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.

SIGNOR-271723

Q15788

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.769

Transactivation of these templates depends on the association of the GR with co-activators such as SRC-1/NcoA1, GRIP-1/TIF-2/NcoA2 and p300/CBP.

SIGNOR-251682

Q15139

Q8NEB9

1

phosphorylation

up-regulates activity

0.371

PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate formation, and autophagosome formation.|Therefore, PKD phosphorylates Vps34 on multiple sites, including Thr677 within the catalytic domain.

SIGNOR-278495

Q13315

Q9H3D4

1

phosphorylation

down-regulates

0.403

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

SIGNOR-180747

P17096

Q9H2X6

0

phosphorylation

down-regulates

0.493

Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.

SIGNOR-158620

Q9UKV8

O00743

0

dephosphorylation

up-regulates activity

0.328

Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.

SIGNOR-276515

Q13950

Q8IYA7

0

transcriptional regulation

up-regulates quantity by expression

0.301

MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).

SIGNOR-267215

O60563

Q92585

0

relocalization

up-regulates

0.2

Cycc:cdk8 and cyct1:cdk9/p-tefb are recruited with notch and associated coactivators (mam, skip) to the hes1 promoter in signaling cells.

SIGNOR-130712

P00533

Q9BV68

0

polyubiquitination

down-regulates quantity by destabilization

0.328

RNF126 and Rabring7 associate with the EGFR through a ubiquitin-binding zinc finger domain and both E3 ubiquitin ligases promote ubiquitylation of EGFR. In HeLa cells depleted of either RNF126 or Rabring7 the EGFR is retained in a late endocytic compartment and is inefficiently degraded.

SIGNOR-272103

Q6ZNA4

P29590

1

polyubiquitination

down-regulates quantity by destabilization

0.355

Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.

SIGNOR-272883

P31749

Q13107

1

phosphorylation

up-regulates quantity by stabilization

0.465

AKT-mediated phosphorylation relocates nuclear USP4 to the cytoplasm and membrane and is required for maintaining its protein stability.

SIGNOR-273482

P51955

Q5T7B8

1

phosphorylation

up-regulates activity

0.695

Nek2 binds and phosphorylates Kif24.|We also provide evidence that Nek2 dependent phosphorylation induces a conformational change in Kif24 that promotes its activity.

SIGNOR-278413

Q8N163

P19784

0

phosphorylation

up-regulates activity

0.2

CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. |In our results, CK2alpha affected the|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1

SIGNOR-267667

Q92793

O75177

0

relocalization

up-regulates

0.397

The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.

SIGNOR-129926

P01574

P03209

0

transcriptional regulation

down-regulates quantity by repression

0.2

Epstein-Barr Virus BRLF1 Inhibits Transcription of IRF3 and IRF7 and Suppresses Induction of Interferon-β. These results suggest that EBV Rta is capable of regulating the activation of the IFN-β promoter.

SIGNOR-266646

P45983

Q96KB5

0

phosphorylation

up-regulates activity

0.303

Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.

SIGNOR-280061

Q96RT7

O00444

0

phosphorylation

up-regulates activity

0.701

Plk4 interacts with and phosphorylates GCP6. we show that GCP6 is an integral component of the centriole and required for centriole duplication. Moreover, we find that GCP6 interacts in vitro and in vivo with Plk4. We show that phosphorylation of GCP6 by Plk4 is required for Plk4-induced centriole overduplication.

SIGNOR-262902

Q8IW41

Q16539

0

phosphorylation

up-regulates activity

0.637

In hela cells, prak was activated in response to cellular stress and proinflammatory cytokines. 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-58135

Q13535

P04637

1

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

P05198

Q9UI10

0

guanine nucleotide exchange factor

up-regulates activity

0.869

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269127

P35221

Q06124

0

dephosphorylation

down-regulates

0.435

Tyr148 of beta-catenin is an shp2 target dephosphorylation site. Together, these results suggest that beta-catenin plays a suppressor role in cell transformation and that shp2, by dephosphorylating beta-catenin, promotes mitogenic, cell survival and transformation signals.

SIGNOR-147075

Q05397

P09619

0

phosphorylation

up-regulates

0.553

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

SIGNOR-167658

P05129

P49768

1

phosphorylation

up-regulates activity

0.2

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-249238

P55085

P08311

0

cleavage

down-regulates activity

0.526

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263585

Q9H4A3

Q9Y3S1

0

phosphorylation

up-regulates activity

0.546

WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.

SIGNOR-260790

Q86Y01

Q96J02

0

ubiquitination

down-regulates

0.7

Itch/aip4 mediates deltex degradation through the formation of k29-linked polyubiquitin chains.

SIGNOR-150002

P35579

P35222

1

transcriptional regulation

up-regulates quantity by expression

0.274

Nuclear MYH9 bound to the CTNNB1 promoter through its DNA-binding domain, and interacted with myosin light chain 9, β-actin and RNA polymerase II to promote CTNNB1 transcription, which conferred resistance to anoikis in GC cells in vitro and in vivo.

SIGNOR-278896

Q16654

P11498

1

phosphorylation

down-regulates activity

0.373

PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.

SIGNOR-278974

Q13115

P45984

1

dephosphorylation

down-regulates

0.606

We assayed the relative ability of mkp-2, pac1, and mkp-1 to dephosphorylate erk2 and the other related map kinases, jnk2 and p38. . Mkp-2 had detectable activity against jnk2, although full inactivation of jnk2 was not observed even at the higher phosphatase concentration.

SIGNOR-40929

Q13363

Q13131

0

phosphorylation

down-regulates

0.2

We found that an activated amp-activated protein kinase (ampk) phosphorylates ctbp1 on ser-158 upon metabolic stresses. Moreover, ampk-mediated phosphorylation of ctbp1 (s158) attenuates the repressive function of ctbp1

SIGNOR-200250

P28482

P24941

1

phosphorylation

up-regulates

0.497

In addition to its role in stimulating cyclin d1 expression and nuclear translocation of cdk2, erk regulates thr-160 phosphorylation of cdk2-cyclin e.

SIGNOR-94003

Q13501

Q14145

1

ubiquitination

down-regulates quantity by destabilization

0.712

When autophagy is impaired, accumulated SQSTM1 interacts with KEAP1, leading to the proteasomal degradation of KEAP1. This interaction sequesters KEAP1 away from NFE2L2, preventing the ubiquitination and degradation of NFE2L2. Consequently, NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins.

SIGNOR-279849

Q8N103

P63000

1

gtpase-activating protein

down-regulates activity

0.402

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-260524

P46019

P22612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267414

P49356

P01112

1

null

up-regulates activity

0.46

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-242565

O14965

P35222

1

phosphorylation

up-regulates quantity

0.346

In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic \u03b2-catenin expression in esophageal squamous cell carcinoma tissues.|We also demonstrate for the first time that Aurora-A directly interacts with \u03b2-catenin and phosphorylates \u03b2-catenin at Ser552 and Ser675.

SIGNOR-278468

Q9HC98

Q9HC35

1

phosphorylation

up-regulates activity

0.253

The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression.

SIGNOR-273883

Q13153

Q14247

1

phosphorylation

up-regulates

0.707

Strikingly, we find that pak1 phosphorylation of cortactin on serine residues 405 and 418 increases its association with n-wasp. Thus, pak1, by controlling the interaction between cortactin and n-wasp, could regulate the polymerization of actin during clathrin-independent endocytosis.

SIGNOR-169690

P49841

P11308

1

phosphorylation

down-regulates quantity by destabilization

0.2

Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively.

SIGNOR-277528

P63000

Q9Y3L3

0

gtpase-activating protein

down-regulates activity

0.38

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-260514

Q9UBK2

P31749

0

phosphorylation

down-regulates activity

0.447

Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1alpha At ser570 Is required for akt to inhibit recruitment of pgc-1alpha To chromatin.

SIGNOR-252502

Q96QP1

Q96CG3

1

phosphorylation

up-regulates activity

0.247

The authors proposed that binding of ADP-Hep caused a conformational change exposing the catalytic cleft and allowing for ALPK1 to phosphorylate and activate TIFA leading to downstream NF-kB activation.

SIGNOR-279789

P06239

Q13444

1

phosphorylation

up-regulates

0.349

Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.

SIGNOR-112931

P17252

P35367

1

phosphorylation

down-regulates

0.2

In this study, we demonstrated that ser396 and ser398 are phosphorylated by pkc and, that phosphorylation of ser398 is particularly involved in pmainduced desensitization of the h1r.

SIGNOR-66015

P12931

Q16595

1

phosphorylation

down-regulates quantity by destabilization

0.2

We found that frataxin can be phosphorylated by Src. Phosphorylation occurs primarily on Y118 and promotes frataxin ubiquitination, a signal for degradation.

SIGNOR-275585

P46937

Q14164

0

phosphorylation

down-regulates quantity by destabilization

0.44

Virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response.

SIGNOR-277355

O15111

Q04206

1

phosphorylation

up-regulates activity

0.847

Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.

SIGNOR-129931

P52565

P17252

0

phosphorylation

down-regulates activity

0.449

PKCalpha phosphorylates RhoGDIalpha at Ser34 to reduce its affinity for RhoA (but not for Rac1 or Cdc42) .

SIGNOR-279097

P36507

P28482

1

phosphorylation

up-regulates

0.744

Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.

SIGNOR-86709

P49336

P68431

1

phosphorylation

down-regulates activity

0.2

However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.

SIGNOR-273171

P12931

O75581

1

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

P67809

P51812

0

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

Q14258

Q7Z434

1

polyubiquitination

down-regulates quantity by destabilization

0.77

We report here that RLR activation triggers MAVS ubiquitination on lysine 7 and 10 by the E3 ubiquitin ligase TRIM25 and marks it for proteasomal degradation concomitantly with downstream signaling.

SIGNOR-272042

P01106

P45984

0

phosphorylation

up-regulates

0.359

The jnk pathway is selectively involved in the c-myc-mediated apoptosis and that the apoptotic function of c-myc is directly regulated by jnk pathway through phosphorylation at ser-62 and ser-71.

SIGNOR-72108

O00308

P24928

1

ubiquitination

down-regulates quantity

0.387

WWP2 ubiquitylates RNA polymerase II for DNA-PK-dependent transcription arrest and repair at DNA breaks|In response to DSBs, WWP2 targets the RNAPII subunit RPB1 for K48-linked ubiquitylation, thereby driving DNA-PK- and proteasome-dependent eviction of RNAPII.

SIGNOR-268851

P31749

P38936

1

phosphorylation

up-regulates quantity by stabilization

0.84

Pim-1, PKC, and Akt1 kinases phosphorylate Thr-145 and Ser-146 sites on p21 protein. Phosphorylation at Thr-145 promotes cytoplasmic translocation and stability of p21. Ser-146 phosphorylation mediated by Akt1 enhances p21 stabilization and promotes cell survival.

SIGNOR-157790

P16885

P07333

0

null

up-regulates

0.369

Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway

SIGNOR-255570

O96017

P54132

1

phosphorylation

down-regulates quantity by destabilization

0.526

We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges.

SIGNOR-276908

P53350

P54274

1

phosphorylation

up-regulates

0.373

Plk1 phosphorylation of trf1 is essential for its binding to telomeres

SIGNOR-179461

Q13164

Q06413

1

phosphorylation

up-regulates

0.766

Bmk1 dramatically enhances the transactivation activity of mef2c by phosphorylating a serine residue at amino acid position 387 in this transcription factor.

SIGNOR-53545

Q92900

Q9Y243

0

phosphorylation

up-regulates activity

0.2

AKT-Mediated UPF1 Phosphorylation at T151 Promotes UPF1 Helicase Activity

SIGNOR-277596

Q13835

P31751

0

phosphorylation

up-regulates quantity by stabilization

0.267

Akt2 phosphorylates PKP1 in vitro. Phosphorylated PKP1 is more resistant to degradation. PKP1 phosphorylation sites identified by peptide microarray analyses and mass spectrometry.

SIGNOR-273494

Q15796

Q9H4A3

0

phosphorylation

up-regulates quantity

0.2

In addition, WNK1 and WNK4 can phosphorylate Smad2, and silencing of WNK1 reduces Smad2 protein levels in HeLa cells, suggesting that WNKs have complex effects on TGFbeta signaling, which itself can promote cancer or act in a tumor suppressing manner.

SIGNOR-280164

P13349

P68400

0

phosphorylation

up-regulates activity

0.307

Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.

SIGNOR-250922

P10415

P45983

0

phosphorylation

down-regulates

0.582

G(2)/m-phase cells proved more susceptible to death signals, and phosphorylation of bcl-2 appeared to be responsible, as a ser70ala substitution restored resistance to apoptosis. We noted that ask1 and jnk1 were normally activated at g(2)/m phase, and jnk was capable of phosphorylating bcl-2..

SIGNOR-72361

P42261

Q13237

0

phosphorylation

up-regulates activity

0.44

In cultured hippocampal neurons, activation of cGKII induces an accumulation of GluR1 on the cellular plasma membrane at extrasynaptic sites, and blockage of cGKII activity prevents the surface increase of GluR1, and also the increase in mEPSC frequency and amplitude, that follows a chemical form of LTP (chemLTP).|In this complex, cGKII phosphorylates GluR1 at serine 845 (S845), a site known to be phosphorylated also by PKA.

SIGNOR-278427

Q9C0H9

P12931

0

phosphorylation

up-regulates activity

0.496

Phosphorylation of multiple tyrosine-containing motifs found on Sin correlated with c-Crk and cellular phosphoprotein binding to Sin as well as increased c-Src activity. These data suggest that (1) SH2 and SH3 ligand sites on Sin cooperatively activate the signaling potential of c-Src, (2) Sin acts as both an activator and a substrate for c-Src, and (3) phosphorylated Sin may serve as a signaling effector molecule for Src by binding to multiple cellular proteins.

SIGNOR-263196

Q7LBC6

Q07869

1

transcriptional regulation

up-regulates quantity by expression

0.2

We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression.

SIGNOR-266637

P68104

P05771

0

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263167

P27361

Q8IZP0

1

phosphorylation

up-regulates

0.454

We show that erk colocalizes with the wrc at lamellipodial leading edges and directly phosphorylates two wrc components: wave2 and abi1.

SIGNOR-172881

P31749

P55265

1

phosphorylation

down-regulates activity

0.281

AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively

SIGNOR-276193