GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P42224	Q13554	0	phosphorylation	up-regulates	0.406	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154771
Q9BYX4	Q96EQ8	0	polyubiquitination	down-regulates quantity by destabilization	0.657	Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.	SIGNOR-271646
Q14449	P49841	0	phosphorylation	down-regulates activity	0.323	Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor\| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.	SIGNOR-264867
Q9Y2T3	P16220	0	transcriptional regulation	up-regulates quantity by expression	0.2	In addition, exposure of the neurons to BDNF increased CREB binding to the cypin promoter and, in line with these data, expression of a dominant negative form of CREB blocked BDNF-promoted increases in cypin protein levels and proximal dendrite branches.	SIGNOR-268968
P20645	O60664	0	relocalization	up-regulates activity	0.73	TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.	SIGNOR-253093
Q04759	O15530	0	phosphorylation	up-regulates	0.572	We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts.	SIGNOR-134869
O14649	Q02156	0	phosphorylation	down-regulates activity	0.2	We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.	SIGNOR-276431
Q8N2W9	Q12888	1	sumoylation	up-regulates	0.637	Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation	SIGNOR-162167
Q969U6	O00444	0	phosphorylation	down-regulates activity	0.543	The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6.	SIGNOR-275476
P15173	Q96NX9	0	transcriptional regulation	down-regulates quantity by repression	0.367	We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.	SIGNOR-261579
P78527	Q9NUW8	1	phosphorylation	up-regulates	0.537	Optimal function of the dna repair enzyme tdp1 requires its phosphorylation by atm and/or dna-pk. Here we show that top1-associated dna double-stranded breaks (dsbs) induce the phosphorylation of tdp1 at s81. This phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated (atm) and dna-dependent protein kinase (dna-pk)	SIGNOR-188776
Q00535	Q8NEB9	1	phosphorylation	down-regulates	0.357	Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.	SIGNOR-165772
P12931	Q06187	1	phosphorylation	up-regulates activity	0.529	This interaction of BTK with SRC kinases transphosphorylated BTK on tyrosine at residue 551, which led to BTK activation.	SIGNOR-251100
Q13114	Q96G74	0	deubiquitination	down-regulates activity	0.775	TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1.	SIGNOR-265873
O00141	P43003	1	phosphorylation	up-regulates activity	0.415	Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1.	SIGNOR-263075
O14965	P25963	1	phosphorylation	down-regulates activity	0.541	The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).\|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through activation of the PI3K and AKT pathway 35, our data demonstrate, for the first time, that AURKA directly binds and phosphorylates the IkappaBalpha subunit, leading to activation of NF-kappaB.	SIGNOR-278912
P31749	P45985	1	phosphorylation	down-regulates	0.594	Akt phosphorylated sek1 on serine 78.	SIGNOR-236494
P16220	P49137	0	phosphorylation	up-regulates activity	0.691	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2.	SIGNOR-166619
Q05655	P18433	1	phosphorylation	up-regulates activity	0.328	In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232.	SIGNOR-249113
Q05513	P09211	1	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276017
Q15418	Q15831	1	phosphorylation	down-regulates activity	0.288	Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cellsBRAFV600E activates downstream molecules, including ERK and p90 ribosomal S6 kinase (RSK), and leads to the phosphorylation of LKB-1 at Ser428 by these kinases. This cascade results in the dissociation of LKB1 from AMPK.	SIGNOR-209871
Q13158	P53350	0	phosphorylation	down-regulates activity	0.459	Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation\| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD	SIGNOR-168204
P49810	P55210	0	cleavage	up-regulates activity	0.318	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261751
P22612	Q92934	1	phosphorylation	down-regulates	0.434	Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.	SIGNOR-81153
Q99814	P41229	1	transcriptional regulation	up-regulates quantity by expression	0.278	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271579
P12931	Q5TCZ1	1	phosphorylation	up-regulates activity	0.64	First, we observed that the co-expression of both activated Src and wild-type Tks5 stimulated gelatin degradation beyond that of Tks5 overexpression alone ( ).\|In melanoma cells Src dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck, for Nck recruitment to invadopodia, and for invadopodia associated matrix degradation activity .	SIGNOR-280134
P35813	P84022	1	dephosphorylation	down-regulates activity	0.622	Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads.	SIGNOR-232110
Q8IYT8	P54646	1	phosphorylation	down-regulates	0.304	We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I	SIGNOR-173089
P49841	P16615	1	phosphorylation	down-regulates activity	0.283	GSK3β-dependent phosphorylation of SERCA2 at serine 663 in human and mouse hearts. Phosphorylation of SERCA2 at serine 663 regulates SERCA2 activity.	SIGNOR-277886
P00519	O00429	1	phosphorylation	up-regulates activity	0.26	In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation.	SIGNOR-277328
Q8IX03	Q15418	0	phosphorylation	up-regulates	0.335	Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.	SIGNOR-203298
P06241	P40259	1	phosphorylation	up-regulates activity	0.672	CD79b cytoplasmic tail-containing GST fusion proteins were phosphorylated in vitro by baculovirus-produced Fyn, >80% of phosphorylation occurred on the N-terminal ITAM tyrosine. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM). pY195 and pY206 in CD79b	SIGNOR-251154
P03952	P14210	1	cleavage	up-regulates activity	0.323	the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.	SIGNOR-256513
Q4G0P3	P43694	1	transcriptional regulation	up-regulates quantity by expression	0.2	HYDIN promotes expression of Gata4 in cardiomyocyte differentiation. HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. GATA4 is a fundamental TF in embryonic heart development and cardiac differentiation, and reduction in GATA4 function results in a diverse range of CHDs	SIGNOR-265479
P16070	Q9UQM7	0	phosphorylation	up-regulates activity	0.2	In previous studies we have demonstrated that a key control point for this receptor is the phosphorylation of CD44 on a conserved cytoplasmic serine residue, Ser(325). This modification is not required for efficient ligand binding, but is an essential component of CD44-dependent cell migration on a hyaluronan substratum. We demonstrate here that cd44 is phosphorylated to high stoichiometry in resting cells and that ca(2+)/calmodulin-dependent protein kinase ii is a cd44 ser(325) kinase.	SIGNOR-109502
Q14493	P62807	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265377
P12931	P20701	1	phosphorylation	down-regulates activity	0.421	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254741
Q15139	P00519	0	phosphorylation	up-regulates	0.339	By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd	SIGNOR-99255
P31749	P24941	1	phosphorylation	up-regulates	0.328	Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity.	SIGNOR-178058
P00533	Q32MZ4	0	transcriptional regulation	down-regulates quantity by repression	0.293	GC-binding factor 2 (GCF2) is a transcriptional repressor that decreases activity of the epidermal growth factor receptor (EGFR) and other genes. \|Deletion mutants of GCF2 revealed that amino acids 429–528 are required for both DNA binding and repression of the EGFR promoter.	SIGNOR-266057
Q8IVH8	Q13233	1	phosphorylation	up-regulates	0.453	With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation	SIGNOR-61814
Q13131	Q16236	1	phosphorylation	up-regulates activity	0.2	MS-based analysis of immunoprecipitated Nrf2 revealed serine 374, 408 and 433 in human Nrf2 to be hyperphosphorylated as a function of activated AMPK. A direct phosphate-transfer by AMPK to those sites was indicated by in vitro kinase assays with recombinant proteins as well as interaction of AMPK and Nrf2 in cells, evident by co-immunoprecipitation. Mutation of serine 374, 408 and 433 to alanine did not markedly affect half-life, nuclear accumulation or induction of reporter gene expression upon Nrf2 activation with sulforaphane. However, some selected endogenous Nrf2 target genes responded with decreased induction when the identified phosphosites were mutated, whereas others remained unaffected.	SIGNOR-277496
Q9H4B4	P60484	1	phosphorylation	down-regulates activity	0.335	Plk3 phosphorylates pten on thr-366 and ser-370. Plk3-mediated phosphorylation facilitates pten stabilization, thereby negatively regulating the pi3k/pdk1/akt1 signaling axis	SIGNOR-168473
P84022	Q9Y5K5	0	deubiquitination	up-regulates activity	0.397	Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases	SIGNOR-232101
P54764	P11362	1	phosphorylation	up-regulates activity	0.402	EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.\|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling.	SIGNOR-280007
O00459	Q13191	0	ubiquitination	down-regulates activity	0.499	Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. it can be postulated that Cbl-b, as an E3 Ub ligase, may play a general role in functional regulation of its target proteins through ubiquitination in a protein degradation-independent manner.	SIGNOR-271424
O75604	P36897	1	deubiquitination	up-regulates activity	0.2	Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.	SIGNOR-273605
Q6IQ22	A2RUS2	0	guanine nucleotide exchange factor	up-regulates activity	0.624	ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.\|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.	SIGNOR-264734
P35222	P31751	0	phosphorylation	up-regulates	0.57	Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.	SIGNOR-152958
O15111	O43524	1	phosphorylation	down-regulates	0.572	Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation.	SIGNOR-124203
Q9UQM7	O95180	1	phosphorylation	down-regulates activity	0.272	we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin.	SIGNOR-277871
Q9P2J9	Q15797	1	dephosphorylation	down-regulates	0.243	We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1.	SIGNOR-144909
Q14232	P05198	1	guanine nucleotide exchange factor	up-regulates activity	0.83	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-269124
P06239	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.586	Loss of tyrosine kinase p56lck in Jurkat cells abolished NFkappaB activation and partially suppressed and delayed phosphorylation of Tyr-42 of IkappaB upon pervanadate treatment. \|Transfection of these cells with wild type Lck but not with mutant Lck F394 followed by H/R induces the tyrosine phosphorylation of inhibitor of nuclear factor kappaB (IkappaBalpha) and transcriptional activation of NFkappaB, and these are inhibited by Lck inhibitors	SIGNOR-249374
P00519	O43586	1	phosphorylation	up-regulates activity	0.597	PSTPIP1 was phosphorylated by c-Abl. Tyr-344 is a major c-Abl phosphorylation site.PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs.	SIGNOR-251431
P17252	Q15139	1	phosphorylation	up-regulates	0.441	These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.	SIGNOR-66666
Q9H4B4	P11388	1	phosphorylation	up-regulates	0.268	The direct phosphorylation of thr(1342) of topoisomerase iialpha by plk3 was demonstrated with an in vitro kinase assay, and overexpression of plk3 induced the phosphorylation of thr(1342) in cellular topoisomerase iialpha. it is possible that plk3 regulates the activity of topoisomerase iia by phosphorylation in a cell-cycle dependent manner. Another possibility is that plk3 regulates the activity of topoisomerase iia when the checkpoint is activated.	SIGNOR-159596
Q00535	O00429	1	phosphorylation	up-regulates activity	0.464	CDK5 activates DRP1 in BTICs.\|To determine if CDK5 could directly phosphorylate DRP1, we performed an in vitro kinase assay with CDK5, its regulatory partner p25 and GST-DRP1 (wild type or S616A mutant) and found that CDK5 directly phosphorylates DRP1 on the S616 site (Fig. 7d).	SIGNOR-278275
Q08378	Q16584	0	phosphorylation	up-regulates activity	0.361	In vitro kinase assays demonstrated that MLK3 directly phosphorylates golgin-160 in the N-terminal head region between residues 96 and 259.	SIGNOR-279065
P52564	P53778	1	phosphorylation	up-regulates	0.659	Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub of the mitogen-activated protein kinase superfamily . the p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms . p38mapks are activated by dual phosphorylation on a t-x-y motif in the activation loop through the action of map kinase kinases	SIGNOR-184134
Q16539	O15297	0	dephosphorylation	down-regulates activity	0.444	Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue	SIGNOR-84793
Q9UGI0	P48729	0	phosphorylation	up-regulates activity	0.2	Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity.	SIGNOR-273621
Q16620	O43559	1	phosphorylation	up-regulates activity	0.602	The tyrosine phosphoryla tion of FRS2/SNT2 was stimulated dependently on the TrkB activation. to explore the possibility that tyrosine residues 417 and 455 on FRS2/SNT2 function as the binding sites for Shp2, we coexpressed Y417F or Y455F phenylalanine mutants and the Y417/455F double phenylalanine mutant of Myc/Histagged FRS2/SNT2 with TrkB. The active TrkB induced somewhat reduced tyrosine phosphorylation of all of the phenylalanine mutants of FRS2/SNT2 in comparison with tyrosine phosphorylation of the wild type	SIGNOR-250202
P46937	Q15208	0	phosphorylation	down-regulates activity	0.383	We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.	SIGNOR-259855
Q13535	P27707	1	phosphorylation	up-regulates activity	0.2	Since activation of dCK by IR was not prevented by KU-60019 at longer times, but could be suppressed if the ATR inhibitor was combined with the ATM inhibitor, we propose that dCK is activated by ATR when ATM is inhibited.\|Taken together, these data indicate that ATR, like ATM [15], can directly phosphorylate dCK at Ser 74 in vitro and thereby increase its activity.Most dCK activators share the feature of inducing DNA damage followed by DNA damage response, a complex signaling network aimed to preserve genome integrity.	SIGNOR-279494
P23327	Q8IXL6	0	phosphorylation	up-regulates activity	0.404	Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.	SIGNOR-273639
P18848	Q9HA77	1	transcriptional regulation	up-regulates quantity by expression	0.257	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-269417
Q8WZ64	P61586	1	gtpase-activating protein	down-regulates activity	0.514	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-260453
P51955	Q96CN5	1	phosphorylation	down-regulates activity	0.37	Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.	SIGNOR-273707
Q96EP1	Q13547	1	polyubiquitination	down-regulates quantity by destabilization	0.394	Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.	SIGNOR-271465
Q5T0F9	P08908	1	transcriptional regulation	down-regulates quantity by repression	0.335	Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression\|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells.	SIGNOR-268298
P04150	P62136	0	dephosphorylation	up-regulates activity	0.291	The current study assessed whether PP1\u03b1 can stimulate GR function and tested two different hypotheses: First, that PP1\u03b1 regulates GR activity through suppression of MDM2 activity by dephosphorylating it at Ser166, thereby reducing the MDM2-mediated ubiquitination of GR and the subsequent proteasomal degradation of the receptor, as shown for the MR and AR ( xref ; xref ); and second, that PP1\u03b1 directly dephosphorylates the GR at a particular site to relieve functional repression as demonstrated for PP2A and PP5 ( xref ; xref ; xref ).\|The involvement of GR-Ser211 phosphorylation supports the assumption that altered subcellular trafficking is a mechanism less likely contributing to the PP1\u03b1-dependent GR activation.	SIGNOR-277161
P27708	P28482	0	phosphorylation	up-regulates	0.382	Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol	SIGNOR-137171
Q9UM73	P23246	1	phosphorylation	down-regulates	0.2	Furthermore, psf was shown to be a direct substrate of purified alk kinase domain in vitro, and psf tyr293 was identified as the site of phosphorylation. Psf phosphorylation also increased its binding to rna and decreased the psf-mediated suppression of gage6 expression.	SIGNOR-155298
P68400	P08238	1	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
Q96E17	Q86UR5	0	relocalization	up-regulates activity	0.416	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264382
Q00987	O15055	1	polyubiquitination	down-regulates quantity by destabilization	0.356	We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation.	SIGNOR-277421
P49137	P07101	1	phosphorylation	up-regulates activity	0.52	MAPKAP-K2 phosphorylates both Ser19 and Ser40 of TH. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation.	SIGNOR-250149
P24821	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Sp1 and Ets1 are potent transactivators of the TN-C promoter.	SIGNOR-261600
P02671	P50281	0	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.\|MMP-14 27YVATRDN g-chain\| 105XDAATLKSR g-chain \| 92LTYNPDES g-chain \|105LTTNIXEXL a-chain\|433LVTSKGDKE a-chain\| 117FXSANNRD a-chain	SIGNOR-263620
Q9NP62	Q9BVJ7	0	dephosphorylation	up-regulates quantity by stabilization	0.464	DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.\|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1.	SIGNOR-276982
O15264	O14733	0	phosphorylation	up-regulates activity	0.436	p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.	SIGNOR-273954
O00141	P17612	0	phosphorylation	up-regulates activity	0.297	In this publication, we demonstrate that cAMP can activate Sgk and that this effect is mediated by PKA, which directly phosphorylates Thr369 in Sgk.	SIGNOR-275972
P08922	P29350	0	dephosphorylation	down-regulates	0.368	Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.	SIGNOR-105922
Q00839	P78527	0	phosphorylation	up-regulates	0.375	We identify heterogeneous nuclear ribonucleoprotein u (hnrnp-u), also termed scaffold attachment factor a (saf-a), as a specific substrate for dna-pk. We show that hnrnp-u is phosphorylated at ser59 by dna-pk in vitro and in cells in response to dna double-strand breaks	SIGNOR-185058
P28827	P40763	1	dephosphorylation	down-regulates activity	0.262	Thus PTPRM suppresses STAT3 signaling in DDIAS-knockdown cells, suggesting that DDIAS promotes the IL-6\u2013mediated STAT3 signaling in malignant cancer cells by inhibiting the PTPRM function.\|We report that PTPRM is a novel STAT3 tyrosine phosphatase and that it negatively regulates STAT3 activation by dephosphorylating Y705 of STAT3 in the presence of IL-6.	SIGNOR-277016
P06241	P18433	0	dephosphorylation	up-regulates	0.658	Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells.	SIGNOR-154796
P60510	Q04206	1	dephosphorylation	up-regulates activity	0.361	Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation	SIGNOR-248549
P15056	P23760	1	phosphorylation	up-regulates activity	0.308	BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.\|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG).	SIGNOR-278435
Q15303	P42229	1	phosphorylation	up-regulates activity	0.811	ERBB4 directly activates STAT5A, in part, through phosphorylation of STAT5A at the regulatory Tyr-694.\|ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.	SIGNOR-279711
P30307	Q9H4B4	0	phosphorylation	up-regulates	0.731	Cdc25c phosphorylation on serine 191 by plk3 promotes its nuclear translocation	SIGNOR-122090
Q9BUB5	P27361	0	phosphorylation	up-regulates	0.576	Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1	SIGNOR-48360
P53350	P41279	0	phosphorylation	up-regulates	0.2	Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210	SIGNOR-92274
P18848	P35638	1	transcriptional regulation	up-regulates quantity by expression	0.816	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260170
P49959	Q15349	0	phosphorylation	down-regulates activity	0.2	Rsk can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with DSBs.\|ribosomal s6 kinase can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with double-stranded breaks.	SIGNOR-280116
Q15797	P28482	0	phosphorylation	down-regulates	0.608	Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3	SIGNOR-161597
P36897	Q15796	1	phosphorylation	up-regulates activity	0.825	Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I receptor, TbetaRI. Phosphorylation sites on Smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals.	SIGNOR-235995
P54646	P49815	1	phosphorylation	up-regulates	0.577	We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.	SIGNOR-149388
O43524	P31749	0	phosphorylation	down-regulates activity	0.91	Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14?3?3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function	SIGNOR-252523
P28482	Q14934	1	phosphorylation	up-regulates	0.283	We demonstrate that p90 ribosomal s6 kinase (rsk) is recruited to the nfat-dna transcription complex upon activation.Bound Rsk phosphorylates ser(676) and potentiates nfatc4 dna binding. Ser(676) is also targeted by the erk map kinase.	SIGNOR-133272

P42224

Q13554

0

phosphorylation

up-regulates

0.406

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154771

Q9BYX4

Q96EQ8

0

polyubiquitination

down-regulates quantity by destabilization

0.657

Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.

SIGNOR-271646

Q14449

P49841

0

phosphorylation

down-regulates activity

0.323

Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.

SIGNOR-264867

Q9Y2T3

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.2

In addition, exposure of the neurons to BDNF increased CREB binding to the cypin promoter and, in line with these data, expression of a dominant negative form of CREB blocked BDNF-promoted increases in cypin protein levels and proximal dendrite branches.

SIGNOR-268968

P20645

O60664

0

relocalization

up-regulates activity

0.73

TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.

SIGNOR-253093

Q04759

O15530

0

phosphorylation

up-regulates

0.572

We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts.

SIGNOR-134869

O14649

Q02156

0

phosphorylation

down-regulates activity

0.2

We have previously shown that carbamylated PAF-induced repolarization abnormalities result from the protein kinase C (PKC) ε-dependent phosphorylation of the two-pore domain potassium channel TASK-1. Further studies identified threonine 383 in the C terminus of human and canine TASK-1 as the phosphorylation site required for PAF-dependent inhibition of the channel.

SIGNOR-276431

Q8N2W9

Q12888

1

sumoylation

up-regulates

0.637

Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation

SIGNOR-162167

Q969U6

O00444

0

phosphorylation

down-regulates activity

0.543

The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6.

SIGNOR-275476

P15173

Q96NX9

0

transcriptional regulation

down-regulates quantity by repression

0.367

We confirmed Dach2 is a Mgn transcriptional repressor that mediates HDAC-dependent regulation by (i) overexpressing Dach2 in myotubes harboring the 133-bp Mgn promoter and (ii) rescuing TSA-mediated Mgn repression by Dach2 knockdown.

SIGNOR-261579

P78527

Q9NUW8

1

phosphorylation

up-regulates

0.537

Optimal function of the dna repair enzyme tdp1 requires its phosphorylation by atm and/or dna-pk. Here we show that top1-associated dna double-stranded breaks (dsbs) induce the phosphorylation of tdp1 at s81. This phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated (atm) and dna-dependent protein kinase (dna-pk)

SIGNOR-188776

Q00535

Q8NEB9

1

phosphorylation

down-regulates

0.357

Thr159 phosphorylation negatively regulates the ptdins3 kinase activity of vps34 and autophagy cdk5/p25, a neuronal cdk shown to play a role in alzheimer's disease, can also phosphorylate thr159 of vps34.

SIGNOR-165772

P12931

Q06187

1

phosphorylation

up-regulates activity

0.529

This interaction of BTK with SRC kinases transphosphorylated BTK on tyrosine at residue 551, which led to BTK activation.

SIGNOR-251100

Q13114

Q96G74

0

deubiquitination

down-regulates activity

0.775

TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1.

SIGNOR-265873

O00141

P43003

1

phosphorylation

up-regulates activity

0.415

Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1.

SIGNOR-263075

O14965

P25963

1

phosphorylation

down-regulates activity

0.541

The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through activation of the PI3K and AKT pathway 35, our data demonstrate, for the first time, that AURKA directly binds and phosphorylates the IkappaBalpha subunit, leading to activation of NF-kappaB.

SIGNOR-278912

P31749

P45985

1

phosphorylation

down-regulates

0.594

Akt phosphorylated sek1 on serine 78.

SIGNOR-236494

P16220

P49137

0

phosphorylation

up-regulates activity

0.691

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2.

SIGNOR-166619

Q05655

P18433

1

phosphorylation

up-regulates activity

0.328

In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232.

SIGNOR-249113

Q05513

P09211

1

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276017

Q15418

Q15831

1

phosphorylation

down-regulates activity

0.288

Negative regulation of the LKB1/AMPK pathway by ERK in human acute myeloid leukemia cellsBRAFV600E activates downstream molecules, including ERK and p90 ribosomal S6 kinase (RSK), and leads to the phosphorylation of LKB-1 at Ser428 by these kinases. This cascade results in the dissociation of LKB1 from AMPK.

SIGNOR-209871

Q13158

P53350

0

phosphorylation

down-regulates activity

0.459

Fas-associated death domain-containing protein (FADD) was first identified as an adapter molecule involved in formation of a death-inducing signaling complex upon Fas stimulation| Plk1 phosphorylates fadd at ser-194 in response to treatment with taxol Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD

SIGNOR-168204

P49810

P55210

0

cleavage

up-regulates activity

0.318

In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.

SIGNOR-261751

P22612

Q92934

1

phosphorylation

down-regulates

0.434

Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.

SIGNOR-81153

Q99814

P41229

1

transcriptional regulation

up-regulates quantity by expression

0.278

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271579

P12931

Q5TCZ1

1

phosphorylation

up-regulates activity

0.64

First, we observed that the co-expression of both activated Src and wild-type Tks5 stimulated gelatin degradation beyond that of Tks5 overexpression alone ( ).|In melanoma cells Src dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck, for Nck recruitment to invadopodia, and for invadopodia associated matrix degradation activity .

SIGNOR-280134

P35813

P84022

1

dephosphorylation

down-regulates activity

0.622

Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads.

SIGNOR-232110

Q8IYT8

P54646

1

phosphorylation

down-regulates

0.304

We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I

SIGNOR-173089

P49841

P16615

1

phosphorylation

down-regulates activity

0.283

GSK3β-dependent phosphorylation of SERCA2 at serine 663 in human and mouse hearts. Phosphorylation of SERCA2 at serine 663 regulates SERCA2 activity.

SIGNOR-277886

P00519

O00429

1

phosphorylation

up-regulates activity

0.26

In this study, we found that c-Abl phosphorylated Drp1 at tyrosine 266, 368 and 449 in vitro and in vivo, which augmented the GTPase activity of Drp1 and promoted Drp1-mediated mitochondrial fragmentation.

SIGNOR-277328

Q8IX03

Q15418

0

phosphorylation

up-regulates

0.335

Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2.

SIGNOR-203298

P06241

P40259

1

phosphorylation

up-regulates activity

0.672

CD79b cytoplasmic tail-containing GST fusion proteins were phosphorylated in vitro by baculovirus-produced Fyn, >80% of phosphorylation occurred on the N-terminal ITAM tyrosine. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM). pY195 and pY206 in CD79b

SIGNOR-251154

P03952

P14210

1

cleavage

up-regulates activity

0.323

the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.

SIGNOR-256513

Q4G0P3

P43694

1

transcriptional regulation

up-regulates quantity by expression

0.2

HYDIN promotes expression of Gata4 in cardiomyocyte differentiation. HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. GATA4 is a fundamental TF in embryonic heart development and cardiac differentiation, and reduction in GATA4 function results in a diverse range of CHDs

SIGNOR-265479

P16070

Q9UQM7

0

phosphorylation

up-regulates activity

0.2

In previous studies we have demonstrated that a key control point for this receptor is the phosphorylation of CD44 on a conserved cytoplasmic serine residue, Ser(325). This modification is not required for efficient ligand binding, but is an essential component of CD44-dependent cell migration on a hyaluronan substratum. We demonstrate here that cd44 is phosphorylated to high stoichiometry in resting cells and that ca(2+)/calmodulin-dependent protein kinase ii is a cd44 ser(325) kinase.

SIGNOR-109502

Q14493

P62807

1

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265377

P12931

P20701

1

phosphorylation

down-regulates activity

0.421

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254741

Q15139

P00519

0

phosphorylation

up-regulates

0.339

By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd

SIGNOR-99255

P31749

P24941

1

phosphorylation

up-regulates

0.328

Akt phosphorylates cdk2 at threonine 39 residue both in vitro and in vivo. Although cdk2 threonine 39 phosphorylation mediated by akt enhances cyclin-a binding, it is dispensable for its basal binding and the kinase activity.

SIGNOR-178058

P00533

Q32MZ4

0

transcriptional regulation

down-regulates quantity by repression

0.293

GC-binding factor 2 (GCF2) is a transcriptional repressor that decreases activity of the epidermal growth factor receptor (EGFR) and other genes. |Deletion mutants of GCF2 revealed that amino acids 429–528 are required for both DNA binding and repression of the EGFR promoter.

SIGNOR-266057

Q8IVH8

Q13233

1

phosphorylation

up-regulates

0.453

With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation

SIGNOR-61814

Q13131

Q16236

1

phosphorylation

up-regulates activity

0.2

MS-based analysis of immunoprecipitated Nrf2 revealed serine 374, 408 and 433 in human Nrf2 to be hyperphosphorylated as a function of activated AMPK. A direct phosphate-transfer by AMPK to those sites was indicated by in vitro kinase assays with recombinant proteins as well as interaction of AMPK and Nrf2 in cells, evident by co-immunoprecipitation. Mutation of serine 374, 408 and 433 to alanine did not markedly affect half-life, nuclear accumulation or induction of reporter gene expression upon Nrf2 activation with sulforaphane. However, some selected endogenous Nrf2 target genes responded with decreased induction when the identified phosphosites were mutated, whereas others remained unaffected.

SIGNOR-277496

Q9H4B4

P60484

1

phosphorylation

down-regulates activity

0.335

Plk3 phosphorylates pten on thr-366 and ser-370. Plk3-mediated phosphorylation facilitates pten stabilization, thereby negatively regulating the pi3k/pdk1/akt1 signaling axis

SIGNOR-168473

P84022

Q9Y5K5

0

deubiquitination

up-regulates activity

0.397

Here, we report a novel interaction between smads and ubiquitin c-terminal hydrolase uch37, a deubiquitinating enzyme that could potentially reverse smurf-mediated ubiquitination. In gst pull down experiments, uch37 bound weakly to smad2 and smad3, and bound very strongly to smad7 in a region that is distinct from the -py- motif in smad7 that interacts with smurf ubiquitin ligases

SIGNOR-232101

P54764

P11362

1

phosphorylation

up-regulates activity

0.402

EphA4 and FGFR1 heterodimer promotes FGFR1 signaling in glioma cell line.|Ligand stimulation of EphA4 stimulates FGFR1 phosphorylation and signaling.

SIGNOR-280007

O00459

Q13191

0

ubiquitination

down-regulates activity

0.499

Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. it can be postulated that Cbl-b, as an E3 Ub ligase, may play a general role in functional regulation of its target proteins through ubiquitination in a protein degradation-independent manner.

SIGNOR-271424

O75604

P36897

1

deubiquitination

up-regulates activity

0.2

Here, we report the role of USP2a in promoting metastasis by facilitating TGF-β-triggered signaling. USP2a interacts with TGFBR1 and TGFBR2 upon TGF-β stimulation and removes K33-linked polyubiquitin chains from Lys502 of TGFBR1, promoting the recruitment of SMAD2/3. Simultaneously, TGFBR2 phosphorylates Ser207/Ser225 of USP2a, leading to the disassociation of SMAD2/3 from TGFBR1.

SIGNOR-273605

Q6IQ22

A2RUS2

0

guanine nucleotide exchange factor

up-regulates activity

0.624

ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.

SIGNOR-264734

P35222

P31751

0

phosphorylation

up-regulates

0.57

Phosphorylation of beta-catenin by akt promotes beta-catenin transcriptional activitywe have demonstrated that akt phosphorylates beta-catenin at ser552 in vitro and in vivo.

SIGNOR-152958

O15111

O43524

1

phosphorylation

down-regulates

0.572

Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation.

SIGNOR-124203

Q9UQM7

O95180

1

phosphorylation

down-regulates activity

0.272

we also discovered that a novel CaMKII-phosphorylated site, S2137, underwent dephosphorylation by calcineurin.

SIGNOR-277871

Q9P2J9

Q15797

1

dephosphorylation

down-regulates

0.243

We show that the mammalian pdps are important in dephosphorylation of bmp-activated smad1 but not tgf-beta-activated smad2 or smad3. Thus, pdps specifically inactivate smads in the bmp/dpp pathway. [...] These observations suggest that pdp1 and pdp2 are important for dephosphorylation of smad1.

SIGNOR-144909

Q14232

P05198

1

guanine nucleotide exchange factor

up-regulates activity

0.83

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-269124

P06239

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.586

Loss of tyrosine kinase p56lck in Jurkat cells abolished NFkappaB activation and partially suppressed and delayed phosphorylation of Tyr-42 of IkappaB upon pervanadate treatment. |Transfection of these cells with wild type Lck but not with mutant Lck F394 followed by H/R induces the tyrosine phosphorylation of inhibitor of nuclear factor kappaB (IkappaBalpha) and transcriptional activation of NFkappaB, and these are inhibited by Lck inhibitors

SIGNOR-249374

P00519

O43586

1

phosphorylation

up-regulates activity

0.597

PSTPIP1 was phosphorylated by c-Abl. Tyr-344 is a major c-Abl phosphorylation site.PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs.

SIGNOR-251431

P17252

Q15139

1

phosphorylation

up-regulates

0.441

These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.

SIGNOR-66666

Q9H4B4

P11388

1

phosphorylation

up-regulates

0.268

The direct phosphorylation of thr(1342) of topoisomerase iialpha by plk3 was demonstrated with an in vitro kinase assay, and overexpression of plk3 induced the phosphorylation of thr(1342) in cellular topoisomerase iialpha. it is possible that plk3 regulates the activity of topoisomerase iia by phosphorylation in a cell-cycle dependent manner. Another possibility is that plk3 regulates the activity of topoisomerase iia when the checkpoint is activated.

SIGNOR-159596

Q00535

O00429

1

phosphorylation

up-regulates activity

0.464

CDK5 activates DRP1 in BTICs.|To determine if CDK5 could directly phosphorylate DRP1, we performed an in vitro kinase assay with CDK5, its regulatory partner p25 and GST-DRP1 (wild type or S616A mutant) and found that CDK5 directly phosphorylates DRP1 on the S616 site (Fig. 7d).

SIGNOR-278275

Q08378

Q16584

0

phosphorylation

up-regulates activity

0.361

In vitro kinase assays demonstrated that MLK3 directly phosphorylates golgin-160 in the N-terminal head region between residues 96 and 259.

SIGNOR-279065

P52564

P53778

1

phosphorylation

up-regulates

0.659

Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub of the mitogen-activated protein kinase superfamily . the p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms . p38mapks are activated by dual phosphorylation on a t-x-y motif in the activation loop through the action of map kinase kinases

SIGNOR-184134

Q16539

O15297

0

dephosphorylation

down-regulates activity

0.444

Wip1 selectively inactivates p38 by specific dephosphorylation of its conserved threonine residue

SIGNOR-84793

Q9UGI0

P48729

0

phosphorylation

up-regulates activity

0.2

Interestingly, ZRANB1 is phosphorylated at Thr35, and Ser209 residues by CSNK1A1, and this phosphorylation activates its deubiquitinating activity.

SIGNOR-273621

Q16620

O43559

1

phosphorylation

up-regulates activity

0.602

The tyrosine phosphoryla tion of FRS2/SNT2 was stimulated dependently on the TrkB activation. to explore the possibility that tyrosine residues 417 and 455 on FRS2/SNT2 function as the binding sites for Shp2, we coexpressed Y417F or Y455F phenylalanine mutants and the Y417/455F double phenylalanine mutant of Myc/Histagged FRS2/SNT2 with TrkB. The active TrkB induced somewhat reduced tyrosine phosphorylation of all of the phenylalanine mutants of FRS2/SNT2 in comparison with tyrosine phosphorylation of the wild type

SIGNOR-250202

P46937

Q15208

0

phosphorylation

down-regulates activity

0.383

We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.

SIGNOR-259855

Q13535

P27707

1

phosphorylation

up-regulates activity

0.2

Since activation of dCK by IR was not prevented by KU-60019 at longer times, but could be suppressed if the ATR inhibitor was combined with the ATM inhibitor, we propose that dCK is activated by ATR when ATM is inhibited.|Taken together, these data indicate that ATR, like ATM [15], can directly phosphorylate dCK at Ser 74 in vitro and thereby increase its activity.Most dCK activators share the feature of inducing DNA damage followed by DNA damage response, a complex signaling network aimed to preserve genome integrity.

SIGNOR-279494

P23327

Q8IXL6

0

phosphorylation

up-regulates activity

0.404

Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.

SIGNOR-273639

P18848

Q9HA77

1

transcriptional regulation

up-regulates quantity by expression

0.257

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-269417

Q8WZ64

P61586

1

gtpase-activating protein

down-regulates activity

0.514

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-260453

P51955

Q96CN5

1

phosphorylation

down-regulates activity

0.37

Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.

SIGNOR-273707

Q96EP1

Q13547

1

polyubiquitination

down-regulates quantity by destabilization

0.394

Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.

SIGNOR-271465

Q5T0F9

P08908

1

transcriptional regulation

down-regulates quantity by repression

0.335

Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells.

SIGNOR-268298

P04150

P62136

0

dephosphorylation

up-regulates activity

0.291

The current study assessed whether PP1\u03b1 can stimulate GR function and tested two different hypotheses: First, that PP1\u03b1 regulates GR activity through suppression of MDM2 activity by dephosphorylating it at Ser166, thereby reducing the MDM2-mediated ubiquitination of GR and the subsequent proteasomal degradation of the receptor, as shown for the MR and AR ( xref ; xref ); and second, that PP1\u03b1 directly dephosphorylates the GR at a particular site to relieve functional repression as demonstrated for PP2A and PP5 ( xref ; xref ; xref ).|The involvement of GR-Ser211 phosphorylation supports the assumption that altered subcellular trafficking is a mechanism less likely contributing to the PP1\u03b1-dependent GR activation.

SIGNOR-277161

P27708

P28482

0

phosphorylation

up-regulates

0.382

Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol

SIGNOR-137171

Q9UM73

P23246

1

phosphorylation

down-regulates

0.2

Furthermore, psf was shown to be a direct substrate of purified alk kinase domain in vitro, and psf tyr293 was identified as the site of phosphorylation. Psf phosphorylation also increased its binding to rna and decreased the psf-mediated suppression of gage6 expression.

SIGNOR-155298

P68400

P08238

1

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

Q96E17

Q86UR5

0

relocalization

up-regulates activity

0.416

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

SIGNOR-264382

Q00987

O15055

1

polyubiquitination

down-regulates quantity by destabilization

0.356

We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation.

SIGNOR-277421

P49137

P07101

1

phosphorylation

up-regulates activity

0.52

MAPKAP-K2 phosphorylates both Ser19 and Ser40 of TH. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation.

SIGNOR-250149

P24821

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Sp1 and Ets1 are potent transactivators of the TN-C promoter.

SIGNOR-261600

P02671

P50281

0

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-14 27YVATRDN g-chain| 105XDAATLKSR g-chain | 92LTYNPDES g-chain |105LTTNIXEXL a-chain|433LVTSKGDKE a-chain| 117FXSANNRD a-chain

SIGNOR-263620

Q9NP62

Q9BVJ7

0

dephosphorylation

up-regulates quantity by stabilization

0.464

DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1.

SIGNOR-276982

O15264

O14733

0

phosphorylation

up-regulates activity

0.436

p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.

SIGNOR-273954

O00141

P17612

0

phosphorylation

up-regulates activity

0.297

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

SIGNOR-275972

P08922

P29350

0

dephosphorylation

down-regulates

0.368

Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.

SIGNOR-105922

Q00839

P78527

0

phosphorylation

up-regulates

0.375

We identify heterogeneous nuclear ribonucleoprotein u (hnrnp-u), also termed scaffold attachment factor a (saf-a), as a specific substrate for dna-pk. We show that hnrnp-u is phosphorylated at ser59 by dna-pk in vitro and in cells in response to dna double-strand breaks

SIGNOR-185058

P28827

P40763

1

dephosphorylation

down-regulates activity

0.262

Thus PTPRM suppresses STAT3 signaling in DDIAS-knockdown cells, suggesting that DDIAS promotes the IL-6\u2013mediated STAT3 signaling in malignant cancer cells by inhibiting the PTPRM function.|We report that PTPRM is a novel STAT3 tyrosine phosphatase and that it negatively regulates STAT3 activation by dephosphorylating Y705 of STAT3 in the presence of IL-6.

SIGNOR-277016

P06241

P18433

0

dephosphorylation

up-regulates

0.658

Ptpalpha is a more widely expressed transmembrane ptp that has been shown to regulate the src family kinases, src and fyn, and is also present in t cells.

SIGNOR-154796

P60510

Q04206

1

dephosphorylation

up-regulates activity

0.361

Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation

SIGNOR-248549

P15056

P23760

1

phosphorylation

up-regulates activity

0.308

BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development.|We found that BRAF clearly induced phosphorylation of PAX3 at Ser205 in both cell types (XREF_FIG).

SIGNOR-278435

Q15303

P42229

1

phosphorylation

up-regulates activity

0.811

ERBB4 directly activates STAT5A, in part, through phosphorylation of STAT5A at the regulatory Tyr-694.|ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events.

SIGNOR-279711

P30307

Q9H4B4

0

phosphorylation

up-regulates

0.731

Cdc25c phosphorylation on serine 191 by plk3 promotes its nuclear translocation

SIGNOR-122090

Q9BUB5

P27361

0

phosphorylation

up-regulates

0.576

Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1

SIGNOR-48360

P53350

P41279

0

phosphorylation

up-regulates

0.2

Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210

SIGNOR-92274

P18848

P35638

1

transcriptional regulation

up-regulates quantity by expression

0.816

ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.

SIGNOR-260170

P49959

Q15349

0

phosphorylation

down-regulates activity

0.2

Rsk can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with DSBs.|ribosomal s6 kinase can phosphorylate the Mre11 protein directly at S676 both in vitro and in intact cells and thereby can inhibit the binding of Mre11 to DNA with double-stranded breaks.

SIGNOR-280116

Q15797

P28482

0

phosphorylation

down-regulates

0.608

Phosphorylation of the linker region of smads mediated by erk2, gsk3?, And cdk2/4 negatively regulates smad activity by preventing their relocation to the nucleus, by inhibiting their interactions with coactivators, or by accelerating their degradation;in contrast, erk2 phosphorylated all four smad1 residues almost evenly, while showing a preference for s204 over s208 and s213 in smad3

SIGNOR-161597

P36897

Q15796

1

phosphorylation

up-regulates activity

0.825

Recently, it was demonstrated that Smad2 interacts transiently with and is a direct substrate of the transforming growth factor-beta (TGF-beta) type I receptor, TbetaRI. Phosphorylation sites on Smad2 were localized to a carboxyl-terminal fragment containing three serine residues at positions 464, 465, and 467. These results indicate that receptor-dependent phosphorylation of Smad2 on serines 465 and 467 is required in mammalian cells to permit association with Smad4 and to propagate TGF-_ signals.

SIGNOR-235995

P54646

P49815

1

phosphorylation

up-regulates

0.577

We have observed that ampk directly phosphorylates tsc2, and the ampk-dependent phosphorylation of tsc2 is critical for the coordination between cell growth and cellular energy levels.

SIGNOR-149388

O43524

P31749

0

phosphorylation

down-regulates activity

0.91

Akt-dependent phosphorylation of foxo3a (thr32, ser253, and ser315 for human foxo3) enhances foxo3a/14?3?3 Interaction and promotes foxo3a nuclear export to the cytoplasm, resulting in the repression of foxo3a transcriptional function

SIGNOR-252523

P28482

Q14934

1

phosphorylation

up-regulates

0.283

We demonstrate that p90 ribosomal s6 kinase (rsk) is recruited to the nfat-dna transcription complex upon activation.Bound Rsk phosphorylates ser(676) and potentiates nfatc4 dna binding. Ser(676) is also targeted by the erk map kinase.

SIGNOR-133272