GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P62993	Q07889	1	relocalization	up-regulates activity	0.912	Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate.	SIGNOR-235773
Q00535	Q99490	1	phosphorylation	up-regulates	0.262	Here, we demonstrate that cyclin dependent kinase 5 (cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates pike-a at ser-279 in its gtpase domain in glioblastoma cells. This phosphorylation event stimulates pike-a gtpase activity and the activity of its downstream effector akt.	SIGNOR-178660
Q99878	Q14493	0	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-265404
P30307	P45984	0	phosphorylation	down-regulates	0.376	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164093
P22681	P29376	0	phosphorylation	up-regulates	0.369	Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.	SIGNOR-49528
Q92820	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.	SIGNOR-261350
Q01813	Q9Y4P1	1	phosphorylation	up-regulates activity	0.2	In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells.	SIGNOR-275832
O60260	Q9Y6H5	1	ubiquitination	down-regulates quantity by destabilization	0.2	Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1.	SIGNOR-278550
P35968	P12931	0	phosphorylation	up-regulates activity	0.614	In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).\|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).	SIGNOR-279120
P68400	Q96HZ4	1	phosphorylation	up-regulates activity	0.498	Hes6 inhibits the interaction of Hes1 with its transcriptional corepressor Gro/TLE. Moreover, it promotes proteolytic degradation of Hes1. This effect is maximal when both Hes1 and Hes6 contain the WRPW motif and is reduced when Hes6 is mutated to eliminate a conserved site (Ser183) that can be phosphorylated by protein kinase CK2.	SIGNOR-250890
Q9UJQ4	Q9H9S0	1	transcriptional regulation	up-regulates quantity by expression	0.792	We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.	SIGNOR-266079
P31751	P99999	1	phosphorylation	down-regulates activity	0.293	Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.	SIGNOR-277236
Q9UNE7	Q9ULG1	1	ubiquitination	up-regulates activity	0.2	Then, by an in vivo ubiquitination assay under denaturing conditions (hereafter, all in vivo ubiquitination assays were carried out under denaturing conditions), we determined whether CHIP ubiquitinates Ino80.\|We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding.	SIGNOR-278646
P35568	P29376	0	phosphorylation	up-regulates	0.314	Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.	SIGNOR-49531
Q9GZY8	Q13131	0	phosphorylation	up-regulates activity	0.2	A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission.	SIGNOR-245953
P68400	Q9UGP8	1	phosphorylation	up-regulates activity	0.291	Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.	SIGNOR-265267
Q00535	P15311	1	phosphorylation	up-regulates activity	0.464	Increased ezrin expression and activation by CDK5 coincident with acquisition of the senescent phenotype.	SIGNOR-250665
Q16555	P49841	0	phosphorylation	down-regulates activity	0.724	Here, we showed that glycogen synthase kinase-3beta (gsk-3beta) phosphorylated crmp-2 at thr-514 and inactivated it	SIGNOR-133255
P12318	P07948	0	phosphorylation	up-regulates activity	0.608	Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn.	SIGNOR-249379
Q13315	Q13362-3	1	phosphorylation	up-regulates activity	0.378	In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.	SIGNOR-276320
Q8WZ42	P17252	0	phosphorylation	up-regulates activity	0.271	In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.\|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.	SIGNOR-278382
Q99683	P31751	0	phosphorylation	down-regulates activity	0.646	Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity	SIGNOR-100588
P49841	P52630	1	phosphorylation	down-regulates quantity by destabilization	0.289	GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.	SIGNOR-276764
Q7Z6Z7	P43405	0	phosphorylation	up-regulates activity	0.2	Collectively, these data suggest that TNF induced tyrosine phosphorylation of Mule by Syk contributes to its E3 ligase activity.	SIGNOR-280150
P43405	P36888	1	phosphorylation	up-regulates activity	0.407	Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).\|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.	SIGNOR-278431
P78527	P11387	1	phosphorylation	down-regulates quantity by destabilization	0.448	Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1.	SIGNOR-277352
Q9NYA4	P84022	1	dephosphorylation	down-regulates	0.517	Here we demonstrate that myotubularin-related protein 4	SIGNOR-163034
Q16539	Q16829	0	dephosphorylation	down-regulates	0.657	The activity of mapks can be also regulated by a family of dusps, which dephosphorylates bot phosphotyrosine and phopsphothreonine residues	SIGNOR-166577
P08069	P35568	1	phosphorylation	up-regulates	0.868	Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor.	SIGNOR-175665
P84022	Q8NG27	0	ubiquitination	down-regulates activity	0.391	In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).	SIGNOR-278832
Q02750	Q5TCX8	0	phosphorylation	up-regulates activity	0.2	These experiments showed that MEK1 is phosphorylated by MLK4 on Ser217/221	SIGNOR-260767
P38936	Q9P1W9	0	phosphorylation	up-regulates quantity by stabilization	0.402	Pim-2 phosphorylation of p21(cip1/waf1) enhances its stability and inhibits cell proliferation in hct116 cellsere we demonstrate that like pim-1, pim-2 also phosphorylates the cell cycle inhibitor p21(cip1/waf1) (p21) on thr145 in vitro and in vivo	SIGNOR-164646
Q8IZL9	P24941	1	phosphorylation	up-regulates	0.387	P42 is essential for the phosphorylation of thr-160 and activation of cdk2.	SIGNOR-118986
Q9ULZ1	Q9BYF1	0	cleavage	up-regulates activity	0.422	ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.	SIGNOR-256316
P56537	P05771	0	phosphorylation	down-regulates activity	0.307	Our results show that release of eIF6 from 60S subunits may operate, in mammalian cells, through a RACK1–PKC betaII pathway. \|Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. \|S235A eIF6 inhibits ribosomal joining in the presence of RACK1–PKCbetaII	SIGNOR-249245
P28329	Q13555	0	phosphorylation	up-regulates activity	0.307	Using mass spectrometry, we identified threonine 456 as a new phosphorylation site in choline acetyltransferase from A beta-(1-42)-treated cells and in purified recombinant ChAT phosphorylated in vitro by calcium/calmodulin-dependent protein kinase II (CaM kinase II). \| This phosphorylation combination was observed in choline acetyltransferase from A beta-(1-42)-treated cells. Treatment of cells with A beta-(1-42) resulted in two phases of activation of choline acetyltransferase, the first within 30 min and associated with phosphorylation by protein kinase C and the second by 10 h and associated with phosphorylation by both CaM kinase II and protein kinase C.	SIGNOR-250693
Q92995	P49761	0	phosphorylation	up-regulates activity	0.2	CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes.	SIGNOR-274122
Q6ZNA4	O15105	1	ubiquitination	down-regulates	0.736	Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia	SIGNOR-119666
P28329	Q05655	0	phosphorylation	up-regulates quantity	0.311	Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.	SIGNOR-249272
Q96BY6	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.522	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-260549
P19784	Q16543	1	phosphorylation	up-regulates activity	0.489	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250982
P14859	P12882	1	transcriptional regulation	up-regulates quantity by expression	0.2	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238760
Q8IXH6	P25098	0	phosphorylation	down-regulates activity	0.2	In conclusion, experimental results demonstrate that GRK2 chronically downregulates DOR functional competence at the PM in peripheral sensory neurons, as well as peripheral DOR anti-nociception in vivo.\|These data demonstrate that BK does not affect GRK2 mediated phosphorylation of DOR at its primary desensitization site.	SIGNOR-279739
Q92753	P04001	1	transcriptional regulation	up-regulates quantity by expression	0.2	These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.	SIGNOR-266851
P41221	Q12857	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268877
P17252	P52566	1	phosphorylation	down-regulates	0.2	These results reveal a mechanism of downregulation of rhogdi2 activity through pkc-mediated phosphorylation of ser31.	SIGNOR-196765
P10398	Q02750	1	phosphorylation	up-regulates	0.74	Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling\|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222.	SIGNOR-235944
P17252	P17302	1	phosphorylation	down-regulates	0.535	Using immunoblotting and phosphospecific antibodies we were able to show that serine-262 (s262) on cx43 becomes phosphorylated in response to growth factor or pkc stimulation of cardiomyocytes.In cell-cell contact forming cultures, the s262d mutation reversed while the s262a mutation increased the inhibitory effect of cx43.Phosphorylation at s262, a pkc site that becomes phosphorylated in the cell environment in response to growth factor stimulation, cancels cx43 inhibition only in contact-forming myocytes.	SIGNOR-120907
Q13315	P37275	1	phosphorylation	up-regulates activity	0.474	Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation.\|Therefore, ATM dependent phosphorylation of ZEB1 at S585 is crucial for IR induced stabilization of ZEB1 but not the interaction between ZEB1 and USP7.	SIGNOR-278329
Q14004	Q13541	1	phosphorylation	up-regulates activity	0.2	CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.	SIGNOR-273113
P01106	P24941	0	phosphorylation	up-regulates quantity by stabilization	0.749	Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ].	SIGNOR-279808
Q04206	Q9P286	0	phosphorylation	up-regulates activity	0.2	PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo\|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1	SIGNOR-275657
P15173	Q12857	0	transcriptional regulation	up-regulates quantity by expression	0.2	NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma\|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,	SIGNOR-263983
P27361	Q13480	1	phosphorylation	up-regulates activity	0.633	Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. \|serine and threonine phosphorylation are capable of modulating the initial signal	SIGNOR-249464
Q9NQ88	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.2	TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. TIGAR is the only known phosphatase glycolytic modulator regulated by TP53. The current study delineates the role of TIGAR in OXPHOS and glycolytic metabolic reprogramming in breast cancer.	SIGNOR-267365
P40763	Q16539	0	phosphorylation	up-regulates	0.621	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-154783
Q8IXJ6	P15259	1	deacetylation	up-regulates activity	0.2	Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.	SIGNOR-266518
P0C0S8	Q5FBB7	1	relocalization	up-regulates activity	0.2	The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.\|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.	SIGNOR-265262
Q96BR1	P49840	1	phosphorylation	down-regulates activity	0.354	Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity\|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.\|The effect of SGK1 was mimicked by PKB and SGK3.	SIGNOR-249165
P06241	P35222	1	phosphorylation	down-regulates activity	0.851	Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins.	SIGNOR-251162
Q13315	Q9H981	1	phosphorylation	down-regulates activity	0.2	These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.\|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.	SIGNOR-279437
P10071	P55075	1	transcriptional regulation	down-regulates quantity	0.445	Whereas Fgf8 expression was almost absent in Shh-/- mutants, it was up-regulated in Gli3-/-;Shh-/- double mutants, suggesting that SHH is not required for Fgf8 induction, and that GLI3 normally represses Fgf8 independently of SHH	SIGNOR-268949
P31749	P12755	1	phosphorylation	down-regulates	0.337	The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7	SIGNOR-252527
P01100	O75676	0	phosphorylation	up-regulates activity	0.392	Serine 374 and serine 362 are the primary sites targeted by Erk1/2 and the mitogen-activated protein kinase-activated kinases Rsk1/2 (12, 13, 37, 38, 41), respectively. Their phosphorylation leads to protein stabilization (3, 13, 20, 41). Threonine 325 and threonine 331 are secondary targets of Erk1/2; their modification occurs only when serines 362 and 374 are phosphorylated and Erk1/2 activation is sufficiently sustained (37, 38). This enhances the transcriptional activity of c-Fos	SIGNOR-263000
Q00535	P47989	1	phosphorylation	up-regulates activity	0.2	Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.\|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.	SIGNOR-280221
Q13418	Q9UMS6	1	phosphorylation	up-regulates activity	0.503	Fourth, ILK dependent phosphorylation of myopodin is found both in vivo and in vitro.\|The ILK dependent activation of myopodin provides a novel link between extracellular matrix-integrin-ILK signaling and myopodin tumor suppression.	SIGNOR-279622
Q5SGD2	Q9Y5P4	1	dephosphorylation	up-regulates activity	0.2	The expression of PP2Cepsilon also enhanced the association between CERT and VAPA.\|These results suggest that CERT is a physiological substrate of PP2Cepsilon and that dephosphorylation of CERT by PP2Cepsilon may play an important role in the regulation of ceramide trafficking from the ER to the Golgi apparatus.	SIGNOR-277113
P45984	O95140	1	phosphorylation	down-regulates	0.351	Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process	SIGNOR-198054
P45985	P05412	1	phosphorylation	up-regulates activity	0.537	SEK1 phosphorylates and activates both p38 and c-Jun NH(2)-terminal kinase (JNK), whereas MKK3 and MKK6 selectively phosphorylate and activate p38.	SIGNOR-279063
P09874	P49959	1	relocalization	up-regulates activity	0.2	PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA.	SIGNOR-272478
P54646	P06241	0	phosphorylation	down-regulates activity	0.257	Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.	SIGNOR-277279
O76064	Q96AP0	1	polyubiquitination	up-regulates quantity by stabilization	0.2	The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres.	SIGNOR-272722
P63000	Q9C0H5	0	gtpase-activating protein	down-regulates activity	0.501	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-260494
Q96CW1	Q5S007	0	phosphorylation	up-regulates activity	0.259	These data confirmed that LRRK2 phosphorylates AP2M1 at Thr 156 in vitro.	SIGNOR-278183
P06241	P36888	1	phosphorylation	up-regulates activity	0.292	FYN phosphorylates FLT3 on tyrosine residues (A\u2013B) COS1 cells were transfected with plasmids expressing FLT3 wild-type and FYN wild-type or mutants.\|It was not completely unexpected that FYN associates wild-type FLT3 in the absence of ligand stimulation in COS-1 cells, as overexpression of wild-type FLT3 results in ligand independent activation of FLT3 (data not shown).	SIGNOR-279715
Q00535	P17600	1	phosphorylation	up-regulates	0.563	Synapsin i (syni), a major sv phosphoprotein involved in the regulation of sv trafficking and neurotransmitter release, is one of the presynaptic substrates of cdk5, which phosphorylates it in its c-terminal region at ser(549) (site 6) and ser(551) (site 7). Phosphorylation of syni by cdk5 is physiologically regulated and enhances its binding to f-actin.	SIGNOR-78883
Q13546	Q6GQQ9	0	deubiquitination	down-regulates activity	0.538	NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne\|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.	SIGNOR-268411
O75582	P27361	0	phosphorylation	up-regulates	0.585	In the present study, we show that, in addition to being phosphorylated on thr-581 and ser-360 by erk1/2 or p38, msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758.	SIGNOR-131379
P31751	Q00987	1	phosphorylation	up-regulates quantity by stabilization	0.56	Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186.	SIGNOR-109732
Q8IWT3	O15392	1	ubiquitination	down-regulates quantity	0.489	CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.\|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.	SIGNOR-278808
O60674	P08887	0	phosphorylation	up-regulates activity	0.569	On binding of IL-6 to its receptor IL-6R, JAK2 is phosphorylated, then STAT3 is phosphorylated by JAK2	SIGNOR-254405
P28482	P22736	1	phosphorylation	up-regulates activity	0.669	NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro.	SIGNOR-249430
Q13127	P53350	0	phosphorylation	down-regulates activity	0.309	Mass spectrometry revealed that PLK1 phosphorylates REST on serine-1030 ( xref and xref ).\|Notably, PLK1 depletion significantly increased REST protein half-life (XREF_FIG, XREF_SUPPLEMENTARY), indicating PLK1 antagonizes REST abundance by restraining REST protein stability.	SIGNOR-279380
Q15303	Q96J02	0	ubiquitination	down-regulates quantity by destabilization	0.606	Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and stimulated degradation of ErbB4 CYT-1	SIGNOR-271416
Q13309	P10244	1	polyubiquitination	down-regulates quantity by destabilization	0.378	P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.	SIGNOR-272572
O14965	Q9UPY8	1	phosphorylation	up-regulates	0.442	Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.	SIGNOR-187657
Q02790	P17706	0	dephosphorylation	down-regulates	0.399	We have documented that a cellular protein that binds the immunosuppressant drug fk506, termed the fk506-binding protein (fkbp52), interacts with the single-stranded d sequence within the aav inverted terminal repeats, inhibits viral second-strand dna synthesis, and consequently limits high-efficiency transgene expression. Deliberate overexpression of the murine wild-type (wt) tc-ptp gene, but not that of a cysteine-to-serine (c-s) mutant, caused tyrosine dephosphorylation of fkbp52, leading to efficient viral second-strand dna synthesis and resulting in a significant increase in aav-mediated transduction efficiency in hela cells in vitro.	SIGNOR-97794
O60741	Q13127	0	transcriptional regulation	down-regulates quantity by repression	0.2	Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites.	SIGNOR-268970
P46937	P31947	0	relocalization	down-regulates activity	0.461	Verteporfin increases the level of 14-3-3σ, which promotes the translocation of YAP from nucleus to cytoplasm.	SIGNOR-278130
Q02556	P19474	0	ubiquitination	down-regulates quantity	0.638	From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.\|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .	SIGNOR-278791
O14757	Q13263	1	phosphorylation	up-regulates activity	0.282	These data suggested that KAP1 Ser473 phosphorylation by Chk1 and Chk2 does not take place predominantly at sites of DNA damage, and are consistent with previous work indicating that, following their DNA-damage-localized phosphorylation and activation by ATR and ATM, Chk1 and Chk2 dissociate from chromatin to phosphorylate their substrates , ].\|These results therefore indicated that both Chk1 and Chk2 can target KAP1 Ser473, and are in agreement with IR triggering both the ATM and Chk2 and ATR and Chk1 pathways .	SIGNOR-280226
Q9Y6H5	P49841	0	phosphorylation	down-regulates	0.487	Synphilin-1 s556a mutant, which is less phosphorylated by gsk3beta, formed more inclusion bodies than wild type synphilin-1. Mutation analysis showed that ser556 is a major gsk3beta phosphorylation site in synphilin-1	SIGNOR-140609
P25098	P25025	1	phosphorylation	down-regulates activity	0.2	Upon activation, GRK2 phosphorylates CXCR2 and causes receptor desensitization and internalization, leading to down-regulation of neutrophil chemotaxis	SIGNOR-260647
Q15796	P27361	0	phosphorylation	down-regulates	0.748	These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3	SIGNOR-66778
P08047	P28482	0	phosphorylation	up-regulates	0.644	Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1.	SIGNOR-116158
O75164	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.339	SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation	SIGNOR-273442
O15455	P00533	0	phosphorylation	up-regulates activity	0.426	Although both the ErbB1 and the ErbB2 isoforms of EGFR can bind to activated TLR3, functionally, only ErbB1 can trigger TLR3 signaling.\|There is a high degree of specificity of the targets of the two PTKs, EGFR and Src	SIGNOR-278932
Q9H257	Q05655	0	phosphorylation	up-regulates activity	0.432	Here we demonstrated that protein kinase C-delta (PKCdelta) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9 and Bcl10 complex assembly and canonical NF-kappaB control.	SIGNOR-278383
P02686	P27361	0	phosphorylation	down-regulates	0.502	Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The identification of myelin basic protein (phosphorylation at -pro-arg-thr-pro-) as a substrate for the erk kinases (fig. 1) demonstrates that there are other determinants important for substrate recognition than those present in the originally identified consensus sequence.	SIGNOR-143481
Q9BUB5	Q13177	0	phosphorylation	down-regulates activity	0.42	Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. When 293T cells are subjected to apoptotic induction by hydrogen peroxide, Mnk1 is phosphorylated at both Thr(22) and Ser(27). These results indicate a role for Pak2 in the down-regulation of translation initiation in apoptosis by phosphorylation of Mnk1.	SIGNOR-250221

P62993

Q07889

1

relocalization

up-regulates activity

0.912

Interaction domains of sos1/grb2 are finely tuned for cooperative control of embryonic stem cell fate.

SIGNOR-235773

Q00535

Q99490

1

phosphorylation

up-regulates

0.262

Here, we demonstrate that cyclin dependent kinase 5 (cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates pike-a at ser-279 in its gtpase domain in glioblastoma cells. This phosphorylation event stimulates pike-a gtpase activity and the activity of its downstream effector akt.

SIGNOR-178660

Q99878

Q14493

0

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-265404

P30307

P45984

0

phosphorylation

down-regulates

0.376

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164093

P22681

P29376

0

phosphorylation

up-regulates

0.369

Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.

SIGNOR-49528

Q92820

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Overexpression of Sp1 led to enhanced GGH promoter activity and GGH mRNA expression in allele-specific manners. These findings suggested that Sp1 acted as a positive regulator of human GGH transcription through the rs3758149 polymorphism in CEM/C1 cells.

SIGNOR-261350

Q01813

Q9Y4P1

1

phosphorylation

up-regulates activity

0.2

In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells.

SIGNOR-275832

O60260

Q9Y6H5

1

ubiquitination

down-regulates quantity by destabilization

0.2

Here we show that parkin interacts with and ubiquitinates the alpha-synuclein-interacting protein, synphilin-1.

SIGNOR-278550

P35968

P12931

0

phosphorylation

up-regulates activity

0.614

In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).

SIGNOR-279120

P68400

Q96HZ4

1

phosphorylation

up-regulates activity

0.498

Hes6 inhibits the interaction of Hes1 with its transcriptional corepressor Gro/TLE. Moreover, it promotes proteolytic degradation of Hes1. This effect is maximal when both Hes1 and Hes6 contain the WRPW motif and is reduced when Hes6 is mutated to eliminate a conserved site (Ser183) that can be phosphorylated by protein kinase CK2.

SIGNOR-250890

Q9UJQ4

Q9H9S0

1

transcriptional regulation

up-regulates quantity by expression

0.792

We conclude that the Nanog enhancer activity is regulated by both Sall4 and Nanog.

SIGNOR-266079

P31751

P99999

1

phosphorylation

down-regulates activity

0.293

Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.

SIGNOR-277236

Q9UNE7

Q9ULG1

1

ubiquitination

up-regulates activity

0.2

Then, by an in vivo ubiquitination assay under denaturing conditions (hereafter, all in vivo ubiquitination assays were carried out under denaturing conditions), we determined whether CHIP ubiquitinates Ino80.|We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding.

SIGNOR-278646

P35568

P29376

0

phosphorylation

up-regulates

0.314

Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.

SIGNOR-49531

Q9GZY8

Q13131

0

phosphorylation

up-regulates activity

0.2

A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission.

SIGNOR-245953

P68400

Q9UGP8

1

phosphorylation

up-regulates activity

0.291

Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.

SIGNOR-265267

Q00535

P15311

1

phosphorylation

up-regulates activity

0.464

Increased ezrin expression and activation by CDK5 coincident with acquisition of the senescent phenotype.

SIGNOR-250665

Q16555

P49841

0

phosphorylation

down-regulates activity

0.724

Here, we showed that glycogen synthase kinase-3beta (gsk-3beta) phosphorylated crmp-2 at thr-514 and inactivated it

SIGNOR-133255

P12318

P07948

0

phosphorylation

up-regulates activity

0.608

Phosphorylation of FcgammaRIIa/c by Lyn is clearly dependent on the presence of Y-298, since all mutants lacking this residue are not phosphorylated by this PTK. This result suggests that Y-298 might be the only tyrosine residue of FcgammaRIIa/c phos- phorylated by Lyn.

SIGNOR-249379

Q13315

Q13362-3

1

phosphorylation

up-regulates activity

0.378

In the present study, we demonstrate that ataxia-telangiectasia mutated (ATM) directly phosphorylates and specifically regulates B56γ3, B56γ2 and B56δ, after DNA damage. We further show that phosphorylation of B56γ3 at Ser510 leads to an increase in B56γ3-PP2A complexes, and direction of PP2A phosphatase activity toward the substrate p53, activating its tumor-suppressive functions. we show that Ser510 phosphorylation significantly enhances the ability of B56γ3 to inhibit cell proliferation and anchorage-independent growth.

SIGNOR-276320

Q8WZ42

P17252

0

phosphorylation

up-regulates activity

0.271

In summary, titin is a PKC substrate with PKCalpha phosphorylating predominately the full-length titin molecule.|Mechanical experiments with skinned LV myocardium revealed that PKCalpha significantly increases titin based passive tension, an effect that is reversed by PP1.

SIGNOR-278382

Q99683

P31751

0

phosphorylation

down-regulates activity

0.646

Akt2 interacts with and phosphorylates ask1 at ser-83 resulting in inhibition of its kinase activity

SIGNOR-100588

P49841

P52630

1

phosphorylation

down-regulates quantity by destabilization

0.289

GSK3α/β are critical kinases to regulate STAT2 protein stability mediated by FBXW7.The 4-point mutant (STAT2-4A) of STAT2 at S381A/T385A/E389A/S393A inhibited GSK3α/β-mediated STAT2 phosphorylation.

SIGNOR-276764

Q7Z6Z7

P43405

0

phosphorylation

up-regulates activity

0.2

Collectively, these data suggest that TNF induced tyrosine phosphorylation of Mule by Syk contributes to its E3 ligase activity.

SIGNOR-280150

P43405

P36888

1

phosphorylation

up-regulates activity

0.407

Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.

SIGNOR-278431

P78527

P11387

1

phosphorylation

down-regulates quantity by destabilization

0.448

Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1.

SIGNOR-277352

Q9NYA4

P84022

1

dephosphorylation

down-regulates

0.517

Here we demonstrate that myotubularin-related protein 4

SIGNOR-163034

Q16539

Q16829

0

dephosphorylation

down-regulates

0.657

The activity of mapks can be also regulated by a family of dusps, which dephosphorylates bot phosphotyrosine and phopsphothreonine residues

SIGNOR-166577

P08069

P35568

1

phosphorylation

up-regulates

0.868

Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor.

SIGNOR-175665

P84022

Q8NG27

0

ubiquitination

down-regulates activity

0.391

In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).

SIGNOR-278832

Q02750

Q5TCX8

0

phosphorylation

up-regulates activity

0.2

These experiments showed that MEK1 is phosphorylated by MLK4 on Ser217/221

SIGNOR-260767

P38936

Q9P1W9

0

phosphorylation

up-regulates quantity by stabilization

0.402

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

SIGNOR-164646

Q8IZL9

P24941

1

phosphorylation

up-regulates

0.387

P42 is essential for the phosphorylation of thr-160 and activation of cdk2.

SIGNOR-118986

Q9ULZ1

Q9BYF1

0

cleavage

up-regulates activity

0.422

ACE2 hydrolyzes the hormone apelin-13 with high catalytic efficiency and cleaves apelin-36, whose C-terminal 13 amino acids are identical to those of apelin-13.

SIGNOR-256316

P56537

P05771

0

phosphorylation

down-regulates activity

0.307

Our results show that release of eIF6 from 60S subunits may operate, in mammalian cells, through a RACK1–PKC betaII pathway. |Loading 60S subunits with eIF6 caused a dose-dependent translational block and impairment of 80S formation, which were reversed by expression of RACK1 and stimulation of PKC in vivo and in vitro. PKC stimulation led to eIF6 phosphorylation, and mutation of a serine residue in the carboxy terminus of eIF6 impaired RACK1/PKC-mediated translational rescue. |S235A eIF6 inhibits ribosomal joining in the presence of RACK1–PKCbetaII

SIGNOR-249245

P28329

Q13555

0

phosphorylation

up-regulates activity

0.307

Using mass spectrometry, we identified threonine 456 as a new phosphorylation site in choline acetyltransferase from A beta-(1-42)-treated cells and in purified recombinant ChAT phosphorylated in vitro by calcium/calmodulin-dependent protein kinase II (CaM kinase II). | This phosphorylation combination was observed in choline acetyltransferase from A beta-(1-42)-treated cells. Treatment of cells with A beta-(1-42) resulted in two phases of activation of choline acetyltransferase, the first within 30 min and associated with phosphorylation by protein kinase C and the second by 10 h and associated with phosphorylation by both CaM kinase II and protein kinase C.

SIGNOR-250693

Q92995

P49761

0

phosphorylation

up-regulates activity

0.2

CLK3 directly phosphorylated USP13 at Y708, which promoted its binding to c-Myc, thereby preventing Fbxl14-mediated c-Myc ubiquitination and activating the transcription of purine metabolic genes.

SIGNOR-274122

Q6ZNA4

O15105

1

ubiquitination

down-regulates

0.736

Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia

SIGNOR-119666

P28329

Q05655

0

phosphorylation

up-regulates quantity

0.311

Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.

SIGNOR-249272

Q96BY6

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.522

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-260549

P19784

Q16543

1

phosphorylation

up-regulates activity

0.489

Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. | In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.

SIGNOR-250982

P14859

P12882

1

transcriptional regulation

up-regulates quantity by expression

0.2

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238760

Q8IXH6

P25098

0

phosphorylation

down-regulates activity

0.2

In conclusion, experimental results demonstrate that GRK2 chronically downregulates DOR functional competence at the PM in peripheral sensory neurons, as well as peripheral DOR anti-nociception in vivo.|These data demonstrate that BK does not affect GRK2 mediated phosphorylation of DOR at its primary desensitization site.

SIGNOR-279739

Q92753

P04001

1

transcriptional regulation

up-regulates quantity by expression

0.2

These observations indicate that RORβ is required for the induction of S opsin and support the conclusion that RORβ regulates Opn1sw transcription in a direct manner through ROREs within its proximal promoter region. In addition, they explain the greatly diminished expression of Opn1sw observed in the retina of RORβ-/- mice.

SIGNOR-266851

P41221

Q12857

0

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268877

P17252

P52566

1

phosphorylation

down-regulates

0.2

These results reveal a mechanism of downregulation of rhogdi2 activity through pkc-mediated phosphorylation of ser31.

SIGNOR-196765

P10398

Q02750

1

phosphorylation

up-regulates

0.74

Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222.

SIGNOR-235944

P17252

P17302

1

phosphorylation

down-regulates

0.535

Using immunoblotting and phosphospecific antibodies we were able to show that serine-262 (s262) on cx43 becomes phosphorylated in response to growth factor or pkc stimulation of cardiomyocytes.In cell-cell contact forming cultures, the s262d mutation reversed while the s262a mutation increased the inhibitory effect of cx43.Phosphorylation at s262, a pkc site that becomes phosphorylated in the cell environment in response to growth factor stimulation, cancels cx43 inhibition only in contact-forming myocytes.

SIGNOR-120907

Q13315

P37275

1

phosphorylation

up-regulates activity

0.474

Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation.|Therefore, ATM dependent phosphorylation of ZEB1 at S585 is crucial for IR induced stabilization of ZEB1 but not the interaction between ZEB1 and USP7.

SIGNOR-278329

Q14004

Q13541

1

phosphorylation

up-regulates activity

0.2

CDK13 directly phosphorylates 4E-BP1 at Thr46 and eIF4B at Ser422; genetically or pharmacologically inhibiting CDK13 disrupts mRNA translation.

SIGNOR-273113

P01106

P24941

0

phosphorylation

up-regulates quantity by stabilization

0.749

Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ].

SIGNOR-279808

Q04206

Q9P286

0

phosphorylation

up-regulates activity

0.2

PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1

SIGNOR-275657

P15173

Q12857

0

transcriptional regulation

up-regulates quantity by expression

0.2

NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma|NFIA has at least three functions on the transcriptional regulation of brown fat [2]. First, NFIA activates adipogenesis per se, through activating the transcription of Pparg, which encodes PPARgamma. Second, NFIA also activates the brown-fat-specific gene expression (such as Ucp1 and Ppargc1a) independent of the degree of adipocyte differentiation, through facilitating the binding of PPARgamma to the brown-fat-specific enhancers. Third, NFIA represses myogenesis through suppression of myogenic transcription factors such as Myod1 as well as Myog,

SIGNOR-263983

P27361

Q13480

1

phosphorylation

up-regulates activity

0.633

Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal

SIGNOR-249464

Q9NQ88

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.2

TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. TIGAR is the only known phosphatase glycolytic modulator regulated by TP53. The current study delineates the role of TIGAR in OXPHOS and glycolytic metabolic reprogramming in breast cancer.

SIGNOR-267365

P40763

Q16539

0

phosphorylation

up-regulates

0.621

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-154783

Q8IXJ6

P15259

1

deacetylation

up-regulates activity

0.2

Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2.

SIGNOR-266518

P0C0S8

Q5FBB7

1

relocalization

up-regulates activity

0.2

The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis, binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1, dephosphorylates cohesin-bound sororin, and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl.|The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1.

SIGNOR-265262

Q96BR1

P49840

1

phosphorylation

down-regulates activity

0.354

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

SIGNOR-249165

P06241

P35222

1

phosphorylation

down-regulates activity

0.851

Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins.

SIGNOR-251162

Q13315

Q9H981

1

phosphorylation

down-regulates activity

0.2

These findings indicate that ATM dependent phosphorylation on ARP8-S412 reduces ARP8 INO80 interaction.|These findings raised the possibility that ATM negatively regulates the interaction of ARP8 with INO80 after etoposide treatment.

SIGNOR-279437

P10071

P55075

1

transcriptional regulation

down-regulates quantity

0.445

Whereas Fgf8 expression was almost absent in Shh-/- mutants, it was up-regulated in Gli3-/-;Shh-/- double mutants, suggesting that SHH is not required for Fgf8 induction, and that GLI3 normally represses Fgf8 independently of SHH

SIGNOR-268949

P31749

P12755

1

phosphorylation

down-regulates

0.337

The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7

SIGNOR-252527

P01100

O75676

0

phosphorylation

up-regulates activity

0.392

Serine 374 and serine 362 are the primary sites targeted by Erk1/2 and the mitogen-activated protein kinase-activated kinases Rsk1/2 (12, 13, 37, 38, 41), respectively. Their phosphorylation leads to protein stabilization (3, 13, 20, 41). Threonine 325 and threonine 331 are secondary targets of Erk1/2; their modification occurs only when serines 362 and 374 are phosphorylated and Erk1/2 activation is sufficiently sustained (37, 38). This enhances the transcriptional activity of c-Fos

SIGNOR-263000

Q00535

P47989

1

phosphorylation

up-regulates activity

0.2

Finally, threonine 222 of XOR is the critical target site for CDK5 dependent activation of XOR.|Once we determined CDK5 was necessary for hypoxia induced hyperactivation of XOR, we tested whether CDK5 was sufficient to phosphorylate XOR and induce increased enzymatic activity in a cell free system.

SIGNOR-280221

Q13418

Q9UMS6

1

phosphorylation

up-regulates activity

0.503

Fourth, ILK dependent phosphorylation of myopodin is found both in vivo and in vitro.|The ILK dependent activation of myopodin provides a novel link between extracellular matrix-integrin-ILK signaling and myopodin tumor suppression.

SIGNOR-279622

Q5SGD2

Q9Y5P4

1

dephosphorylation

up-regulates activity

0.2

The expression of PP2Cepsilon also enhanced the association between CERT and VAPA.|These results suggest that CERT is a physiological substrate of PP2Cepsilon and that dephosphorylation of CERT by PP2Cepsilon may play an important role in the regulation of ceramide trafficking from the ER to the Golgi apparatus.

SIGNOR-277113

P45984

O95140

1

phosphorylation

down-regulates

0.351

Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process

SIGNOR-198054

P45985

P05412

1

phosphorylation

up-regulates activity

0.537

SEK1 phosphorylates and activates both p38 and c-Jun NH(2)-terminal kinase (JNK), whereas MKK3 and MKK6 selectively phosphorylate and activate p38.

SIGNOR-279063

P09874

P49959

1

relocalization

up-regulates activity

0.2

PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA.

SIGNOR-272478

P54646

P06241

0

phosphorylation

down-regulates activity

0.257

Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.

SIGNOR-277279

O76064

Q96AP0

1

polyubiquitination

up-regulates quantity by stabilization

0.2

The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres.

SIGNOR-272722

P63000

Q9C0H5

0

gtpase-activating protein

down-regulates activity

0.501

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-260494

Q96CW1

Q5S007

0

phosphorylation

up-regulates activity

0.259

These data confirmed that LRRK2 phosphorylates AP2M1 at Thr 156 in vitro.

SIGNOR-278183

P06241

P36888

1

phosphorylation

up-regulates activity

0.292

FYN phosphorylates FLT3 on tyrosine residues (A\u2013B) COS1 cells were transfected with plasmids expressing FLT3 wild-type and FYN wild-type or mutants.|It was not completely unexpected that FYN associates wild-type FLT3 in the absence of ligand stimulation in COS-1 cells, as overexpression of wild-type FLT3 results in ligand independent activation of FLT3 (data not shown).

SIGNOR-279715

Q00535

P17600

1

phosphorylation

up-regulates

0.563

Synapsin i (syni), a major sv phosphoprotein involved in the regulation of sv trafficking and neurotransmitter release, is one of the presynaptic substrates of cdk5, which phosphorylates it in its c-terminal region at ser(549) (site 6) and ser(551) (site 7). Phosphorylation of syni by cdk5 is physiologically regulated and enhances its binding to f-actin.

SIGNOR-78883

Q13546

Q6GQQ9

0

deubiquitination

down-regulates activity

0.538

NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination.

SIGNOR-268411

O75582

P27361

0

phosphorylation

up-regulates

0.585

In the present study, we show that, in addition to being phosphorylated on thr-581 and ser-360 by erk1/2 or p38, msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758.

SIGNOR-131379

P31751

Q00987

1

phosphorylation

up-regulates quantity by stabilization

0.56

Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.. Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186.

SIGNOR-109732

Q8IWT3

O15392

1

ubiquitination

down-regulates quantity

0.489

CUL9 promotes the ubiquitylation and degradation of survivin and is inhibited by CUL7.|Together, these results demonstrate the specificity of survivin ubiquitylation by CUL9 E3 ligase complex.

SIGNOR-278808

O60674

P08887

0

phosphorylation

up-regulates activity

0.569

On binding of IL-6 to its receptor IL-6R, JAK2 is phosphorylated, then STAT3 is phosphorylated by JAK2

SIGNOR-254405

P28482

P22736

1

phosphorylation

up-regulates activity

0.669

NGFI-B is an inducible orphan nuclear receptor that initiates apoptosis. Growth factors such as EGF activate the MAP kinase ERK, whose activity may determine if a cell survives or undergoes apoptosis. EGF stimulation of cells leads to phosphorylation of threonine in NGFI-B. Thr-142 of NGFI-B is comprised in a consensus MAP kinase site and was identified as a preferred substrate for ERK2 (but not ERK1) in vitro.

SIGNOR-249430

Q13127

P53350

0

phosphorylation

down-regulates activity

0.309

Mass spectrometry revealed that PLK1 phosphorylates REST on serine-1030 ( xref and xref ).|Notably, PLK1 depletion significantly increased REST protein half-life (XREF_FIG, XREF_SUPPLEMENTARY), indicating PLK1 antagonizes REST abundance by restraining REST protein stability.

SIGNOR-279380

Q15303

Q96J02

0

ubiquitination

down-regulates quantity by destabilization

0.606

Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and stimulated degradation of ErbB4 CYT-1

SIGNOR-271416

Q13309

P10244

1

polyubiquitination

down-regulates quantity by destabilization

0.378

P19Skp1 and Cul-1 bind to the F-box protein p45Skp2 to form a complex (SCF) that functions as E3 ubiquitin ligase.We show that B-Myb physically and functionally interacts with components of the Cdc34-SCFp45Skp2 ubiquitin pathway and propose that B-Myb degradation may be required for controlling the correct alternation of events during progression through the cell division cycle.

SIGNOR-272572

O14965

Q9UPY8

1

phosphorylation

up-regulates

0.442

Aurora-a and aurora-b phosphorylate eb3 at ser-176 in a spatial and cell cycle-specific manner, respectively during mitosis two kinases, aurora-a and aurora-b, phosphorylate eb3 at ser-176, and the resulting phosphorylation disrupts the eb3-siah-1 complex. Indeed, eb3 is stabilized during mitosis and facilitates cell cycle progression.

SIGNOR-187657

Q02790

P17706

0

dephosphorylation

down-regulates

0.399

We have documented that a cellular protein that binds the immunosuppressant drug fk506, termed the fk506-binding protein (fkbp52), interacts with the single-stranded d sequence within the aav inverted terminal repeats, inhibits viral second-strand dna synthesis, and consequently limits high-efficiency transgene expression. Deliberate overexpression of the murine wild-type (wt) tc-ptp gene, but not that of a cysteine-to-serine (c-s) mutant, caused tyrosine dephosphorylation of fkbp52, leading to efficient viral second-strand dna synthesis and resulting in a significant increase in aav-mediated transduction efficiency in hela cells in vitro.

SIGNOR-97794

O60741

Q13127

0

transcriptional regulation

down-regulates quantity by repression

0.2

Levels of NRSF and its physical binding to the Hcn1 gene were augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1 pyramidal cell dendrites.

SIGNOR-268970

P46937

P31947

0

relocalization

down-regulates activity

0.461

Verteporfin increases the level of 14-3-3σ, which promotes the translocation of YAP from nucleus to cytoplasm.

SIGNOR-278130

Q02556

P19474

0

ubiquitination

down-regulates quantity

0.638

From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref .

SIGNOR-278791

O14757

Q13263

1

phosphorylation

up-regulates activity

0.282

These data suggested that KAP1 Ser473 phosphorylation by Chk1 and Chk2 does not take place predominantly at sites of DNA damage, and are consistent with previous work indicating that, following their DNA-damage-localized phosphorylation and activation by ATR and ATM, Chk1 and Chk2 dissociate from chromatin to phosphorylate their substrates , ].|These results therefore indicated that both Chk1 and Chk2 can target KAP1 Ser473, and are in agreement with IR triggering both the ATM and Chk2 and ATR and Chk1 pathways .

SIGNOR-280226

Q9Y6H5

P49841

0

phosphorylation

down-regulates

0.487

Synphilin-1 s556a mutant, which is less phosphorylated by gsk3beta, formed more inclusion bodies than wild type synphilin-1. Mutation analysis showed that ser556 is a major gsk3beta phosphorylation site in synphilin-1

SIGNOR-140609

P25098

P25025

1

phosphorylation

down-regulates activity

0.2

Upon activation, GRK2 phosphorylates CXCR2 and causes receptor desensitization and internalization, leading to down-regulation of neutrophil chemotaxis

SIGNOR-260647

Q15796

P27361

0

phosphorylation

down-regulates

0.748

These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3

SIGNOR-66778

P08047

P28482

0

phosphorylation

up-regulates

0.644

Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1.

SIGNOR-116158

O75164

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.339

SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal degradation

SIGNOR-273442

O15455

P00533

0

phosphorylation

up-regulates activity

0.426

Although both the ErbB1 and the ErbB2 isoforms of EGFR can bind to activated TLR3, functionally, only ErbB1 can trigger TLR3 signaling.|There is a high degree of specificity of the targets of the two PTKs, EGFR and Src

SIGNOR-278932

Q9H257

Q05655

0

phosphorylation

up-regulates activity

0.432

Here we demonstrated that protein kinase C-delta (PKCdelta) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9 and Bcl10 complex assembly and canonical NF-kappaB control.

SIGNOR-278383

P02686

P27361

0

phosphorylation

down-regulates

0.502

Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The identification of myelin basic protein (phosphorylation at -pro-arg-thr-pro-) as a substrate for the erk kinases (fig. 1) demonstrates that there are other determinants important for substrate recognition than those present in the originally identified consensus sequence.

SIGNOR-143481

Q9BUB5

Q13177

0

phosphorylation

down-regulates activity

0.42

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

SIGNOR-250221