GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P25963	P19525	0	phosphorylation	down-regulates quantity by destabilization	0.532	As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kappa B inhibitor I kappa B alpha at serine 32 before degradation.	SIGNOR-249335
P51114	Q13153	0	phosphorylation	up-regulates activity	0.271	Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.	SIGNOR-273713
Q13541	Q9P1W9	0	phosphorylation	up-regulates activity	0.414	Further, PIM2 triggered phosphorylation of AKT and 4EBP1 (XREF_FIG) clearly demonstrating the activation of PI3K pathway.	SIGNOR-279091
P09936	P0CG48	1	cleavage	up-regulates quantity	0.864	These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains	SIGNOR-249693
P55087	P68400	0	phosphorylation	down-regulates activity	0.416	We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression. \| To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4-Cter proteins in which only one out of the three C-terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII.	SIGNOR-250827
O00763	P54646	0	phosphorylation	down-regulates activity	0.649	The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK.	SIGNOR-250318
P23769	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.355	GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).	SIGNOR-276884
Q9UM73	P31939	1	phosphorylation	up-regulates activity	0.377	ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.	SIGNOR-276171
Q16549	P67775	1	phosphorylation	up-regulates	0.2	This together with the rapid kinetics of pp1-pp2a activation following p38 activation suggests that pp1 and/or pp2a complexes are direct targets for p38-mediated phosphorylation	SIGNOR-105783
P07101	Q00535	0	phosphorylation	up-regulates activity	0.408	In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.\|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.	SIGNOR-279022
P17612	P01100	1	phosphorylation	up-regulates activity	0.518	Human c-Fos protein is phosphorylated in vitro by PKA. phosphorylation of Fos occurs at serine residue 362. Modification of the Fos protein by phosphorylation with PKA then allows it to act as a regulator of its own synthesis by downregulating fos gene expression at a transcriptional level	SIGNOR-250356
O15350	Q96J02	0	ubiquitination	down-regulates quantity by destabilization	0.566	Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells	SIGNOR-278699
P52945	P78527	0	phosphorylation	down-regulates quantity by destabilization	0.307	The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.	SIGNOR-225542
P46531	P78536	0	cleavage	up-regulates activity	0.739	... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases.	SIGNOR-78903
P31749	O14746	1	phosphorylation	up-regulates	0.732	Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins.	SIGNOR-67313
Q9NYY3	P04637	1	phosphorylation	up-regulates activity	0.592	Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop.	SIGNOR-278980
P35125	P63000	0	relocalization	up-regulates	0.338	In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.	SIGNOR-98938
Q13535	P09874	1	phosphorylation	down-regulates	0.357	Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.\|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.	SIGNOR-278506
Q6UB99	P51153	1	transcriptional regulation	up-regulates quantity by expression	0.2	Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.	SIGNOR-266738
P53350	Q8IWB6	1	phosphorylation	down-regulates quantity by destabilization	0.354	We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.	SIGNOR-273529
Q13489	Q99558	1	ubiquitination	down-regulates	0.65	Ciap1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate nik for degradation.	SIGNOR-167298
P17252	Q13188	0	phosphorylation	up-regulates activity	0.2	Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.	SIGNOR-277176
O15550	P31276	1	transcriptional regulation	up-regulates quantity by expression	0.267	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260027
P37231	P25025	1	transcriptional regulation	up-regulates quantity by expression	0.264	EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE).	SIGNOR-271682
Q13131	P10636-2	1	phosphorylation	down-regulates activity	0.2	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275438
P31749	Q9BPZ7	1	phosphorylation	up-regulates activity	0.703	Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.	SIGNOR-276932
Q4G163	Q9UQM7	0	phosphorylation	up-regulates activity	0.403	CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. \| these results implicate the 192RSST motif of Emi2 as a critical molecular target of CaMKII during CSF release	SIGNOR-260907
P67809	Q7Z6E9	0	ubiquitination	down-regulates quantity by destabilization	0.317	RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1	SIGNOR-271773
Q15661	O75030	0	transcriptional regulation	up-regulates quantity by expression	0.2	The transcription of tryptase gene in human mast cells is regulated by mi transcription factor \|Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A.	SIGNOR-251725
P28482	Q02548	1	phosphorylation	down-regulates activity	0.351	In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.	SIGNOR-269087
P06493	P18754	1	phosphorylation	up-regulates activity	0.504	We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of hum an RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. However, when both S2 and S11 were simultaneously mutated to As, the resulting 6His-RCC1S2,11A failed to be phosphorylated, whereas all of the other double mutants were phosphorylated (Fig. 1C). As expected, mutating all four sites to As (the 6His-RCC1S2,11,387A-T274A) also blocked phosphorylation (Fig. 1C).	SIGNOR-262704
P28482	O75030	1	phosphorylation	down-regulates	0.705	The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73the results suggested that s1p reduced melanin synthesis via s1p(3) receptor-mediated erk and rsk-1 activation, and subsequent mitf dual phosphorylation and degradation.	SIGNOR-75030
Q13485	P01106	1	transcriptional regulation	down-regulates quantity by repression	0.64	Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter.	SIGNOR-251493
P24385	P03372	0	transcriptional regulation	up-regulates quantity by expression	0.754	Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1.	SIGNOR-135053
Q05397	P23470	0	dephosphorylation	up-regulates activity	0.243	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254719
P17302	P27361	0	phosphorylation	down-regulates activity	0.637	These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication.	SIGNOR-249466
Q15554	P55795	0	post transcriptional regulation	down-regulates quantity	0.332	During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.	SIGNOR-266806
Q9NP97	P17612	0	phosphorylation	up-regulates	0.2	Our results show that km23-1 is required for camp-responsive element (cre) transcriptional activation by tgf_, with s73-km23-1 being required for the cre-dependent tgf_ stimulation of fibronectin (fn) transcription.	SIGNOR-200456
Q9NP77	P24928	1	dephosphorylation	up-regulates activity	0.855	Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.\| Depletion of Ssu72 impairs transcription in vitro	SIGNOR-248815
O75569	P19525	0	phosphorylation	up-regulates activity	0.796	In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR.	SIGNOR-280003
Q6P0Q8	P60484	1	phosphorylation	up-regulates	0.666	We further demonstrate that binding of pten to specific pdz domains diminishes its degradation rate and facilitates its phosphorylation by mast kinases. Our results suggest a regulatory role of pdz domain binding on pten function by controlling its stability and phosphorylation status.	SIGNOR-138051
P40763	P00519	0	phosphorylation	up-regulates activity	0.445	Previously, we showed that c-Abl and Arg promote phosphorylation of the STAT3 transcription factor (Y705) in a variety of cancer cell lines , .\|Since c-Abl and Arg activate STAT3, we investigated whether c-Abl and Arg regulate NF-kappaB signaling.	SIGNOR-279675
Q9NQC7	Q12933	1	deubiquitination	down-regulates activity	0.677	Cyld also interacts directly with tumour-necrosis factor receptor (tnfr)-associated factor 2 (traf2), an adaptor molecule involved in by members of the family of tnf/nerve growth factor receptors. (articolo-abstract)	SIGNOR-117860
Q14155	P05129	0	phosphorylation	up-regulates	0.2	Pkc_ directly phosphorylates _pix at ser583 and indirectly at ser340 in cells. herefore, we propose that pkc_ positively modulates dopamine release through _2pix phosphorylation. The pkc_-_pix-cdc42/rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome	SIGNOR-205238
Q13547	P00519	0	phosphorylation	up-regulates activity	0.507	Despite the fact that HDAC1 was phosphorylated by co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by mutations in its sites phosphorylated by c-Abl.\|c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity dependent manner.	SIGNOR-280169
P12270	P28482	0	phosphorylation	up-regulates	0.374	Tpr is phosphorylated by erk2 at four different sites. / because phosphorylation of tpr by activated erk stabilizes their interaction, we hypothesize that this phosphorylation is not part of a signal amplification cascade but rather positions activated erk to perform a continuing function in the nuclear pore.	SIGNOR-181022
O15111	P35222	1	phosphorylation	up-regulates quantity	0.485	Interestingly, while IKK2 negatively regulates beta-catenin stability similar to GSK3beta, IKK1 seems to increase beta-catenin protein level and downstream signal, such as cyclin D1 transcription.\|These results suggested IKK1 may phosphorylate beta-catenin at different residues and protect it from ubiquitination mediated degradation.	SIGNOR-280230
P53350	O60566	1	phosphorylation	up-regulates	0.84	We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.	SIGNOR-157646
P84022	Q9H6Z4	0	relocalization	down-regulates	0.389	Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner	SIGNOR-184608
P06239	Q9UHD2	1	phosphorylation	down-regulates activity	0.2	The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.	SIGNOR-276724
Q9Y4C1	O60674	0	phosphorylation	up-regulates activity	0.2	KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2 phosphorylates KDM3A at tyrosine 1101 residue.	SIGNOR-277884
Q14790	P27361	0	phosphorylation	down-regulates	0.717	We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity	SIGNOR-203480
P06493	P36956	1	phosphorylation	up-regulates	0.287	Cdk1/cyclin b-mediated phosphorylation stabilizes srebp1 during mitosis.	SIGNOR-148354
Q8TD19	Q92974	1	phosphorylation	up-regulates activity	0.2	The phosphorylation of ARHGEF2 by NEK9 is the key step of this process.	SIGNOR-279638
Q15349	P42345	0	phosphorylation	up-regulates activity	0.392	Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref	SIGNOR-279232
P0DTC2	P07858	0	cleavage	up-regulates activity	0.2	SARS-2-S can use both CatB/L as well as TMPRSS2 for priming in these cell lines.	SIGNOR-260738
Q96PM5	P50750	0	phosphorylation	down-regulates	0.46	We showed that cdk9 phosphorylates pirh2 on ser-211 and thr-217 residues through their physical interaction. Phosphorylation of pirh2 renders it inactive and may contribute to p53-inhibition of transcriptional elongation of the hiv-1 ltr.	SIGNOR-201923
P29350	P78314	1	dephosphorylation	down-regulates	0.57	Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling	SIGNOR-146508
P68400	Q9Y365	1	phosphorylation	down-regulates	0.409	Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity	SIGNOR-155740
O60674	P20701	1	phosphorylation	up-regulates activity	0.268	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-254739
Q9UQD0	Q13555	0	phosphorylation	up-regulates activity	0.271	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275794
O95644	Q16539	0	phosphorylation	down-regulates	0.622	We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.	SIGNOR-74560
Q12802	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.744	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-260527
Q9UHC6	Q6ZVD7	0	transcriptional regulation	down-regulates quantity by repression	0.2	In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.	SIGNOR-269065
Q13451	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.306	These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.	SIGNOR-264542
Q05655	P15941	1	phosphorylation	up-regulates	0.336	We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin	SIGNOR-115501
Q9Y572	Q8NB16	1	phosphorylation	up-regulates activity	0.753	MLKL comprises a four-helical bundle tethered to the pseudokinase domain, which contains an unusual pseudoactive site. Although the pseudokinase domain binds ATP, it is catalytically inactive and its essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation.[...]S345, S347, and T349 in the MLKL activation loop were phosphorylated by RIPK3 in in vitro kinase assays	SIGNOR-266427
P55036	O43255	0	polyubiquitination	down-regulates quantity by destabilization	0.432	S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.	SIGNOR-272748
P32927	P29350	0	dephosphorylation	down-regulates	0.522	However, inhibition of shp2 binding to betac, did not prevent tyrosine phosphorylation of shp2. Interestingly, this same phosphopeptide served as a substrate for the tyrosine phosphatase activity of both shp1 and shp2.	SIGNOR-114597
P07947	P09086	1	phosphorylation	up-regulates activity	0.2	These data suggest that Yes1 is the TKI-sensitive kinase that can directly phosphorylate OCT2.	SIGNOR-279664
O14950	O75116	0	phosphorylation	up-regulates activity	0.598	In addition, an in vitro kinase assay with mixed recombinant GST-ROCK2 and MLC2 revealed that ROCK2 phosphorylated WT MLC2, but not MLC2 S15A mutant, indicating that it phosphorylates MLC2 at S15 in vitro (XREF_FIG).	SIGNOR-279103
Q9UNE7	Q15797	1	ubiquitination	down-regulates	0.328	These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins.	SIGNOR-120731
P14923	P06241	0	phosphorylation	up-regulates activity	0.561	Phosphorylation of plakoglobin by Fer and Fyn kinases decreases plakoglobin-desmoplakin interaction and increases plakoglobin-α-catenin association. Fyn mainly phosphorylated Tyr549 and that it phosphorylated Tyr133 with a much lower activity	SIGNOR-251176
Q8NBP7	Q8IXL6	0	phosphorylation	up-regulates activity	0.537	Herein, we report that Fam20C and Fam20A significantly eliminate the Furin-cleavage of PCSK9 (XREF_FIG, lanes 5, 6), thereby enhancing the pPCSK9 activity\|Herein, we show that Fam20C phosphorylates PCSK9 at Serines 47, 666, 668 and 688.	SIGNOR-278935
Q6IQ55	Q99550	1	phosphorylation	down-regulates quantity	0.2	Additionally, in vivo ubiquitin assays showed that expression of either the kinase-dead TTBK2 or the MPP9-S629 and S636-2A mutant significantly decreased the ubiquitination level of MPP9.\|Also, the S629A mutant almost abolished the phosphorylation of MPP9 by TTBK2 in the kinase assay in vitro, suggesting that S629 is the main site for MPP9 phosphorylation by TTBK2.	SIGNOR-278998
P46937	P35813	0	dephosphorylation	up-regulates activity	0.269	Although the authors show an in vitro kinase assay where PPM1A supposedly dephosphorylates YAP on Ser127, Fig. 4A lacks a positive control to ensure that PPM1A purified from cells is active.\|The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration.	SIGNOR-276984
Q9HD43	P10912	1	dephosphorylation	down-regulates activity	0.295	Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR	SIGNOR-248802
Q15797	O15194	0	dephosphorylation	down-regulates activity	0.498	Smad proteins transduce bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFbeta) signals upon phosphorylation of their C-terminal SXS motif by receptor kinases.\|Phosphatases that dephosphorylate the linker region are therefore likely to play an integral part in the regulation of Smad activity. We reported previously that small C-terminal domain phosphatases 1, 2, and 3 (SCP1-3) dephosphorylate Smad1 C-terminal tail, thereby attenuating BMP signaling. \|The linker region of Smad1 consists of four MAPK phosphorylation sites (Ser-187, Ser-195, Ser-206, and Ser-214)	SIGNOR-248314
P48730	P04637	1	phosphorylation	up-regulates	0.578	Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).	SIGNOR-75889
P24941	P12272	1	phosphorylation	down-regulates	0.372	Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization	SIGNOR-68548
P12931	P52735	1	phosphorylation	up-regulates activity	0.527	Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.\|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2.	SIGNOR-280138
P07202	Q06710	0	transcriptional regulation	up-regulates quantity by expression	0.399	TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.	SIGNOR-267277
P36507	P67775	0	dephosphorylation	down-regulates	0.493	In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.	SIGNOR-166652
O14994	P27361	0	phosphorylation	up-regulates	0.2	A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.	SIGNOR-121402
P03372	P00533	0	phosphorylation	up-regulates	0.59	Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er	SIGNOR-115734
P11168	P52945	0	transcriptional regulation	up-regulates quantity by expression	0.522	In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.	SIGNOR-255540
P29353	P09619	0	phosphorylation	up-regulates	0.659	In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc.	SIGNOR-36906
Q16665	P01588	1	transcriptional regulation	up-regulates quantity by expression	0.643	Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates hypoxia-inducible genes including the human erythropoietin (EPO) gene.	SIGNOR-253695
P28482	Q96RK0	1	phosphorylation	down-regulates	0.372	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3	SIGNOR-169875
P48729	O60346	1	phosphorylation	down-regulates quantity by destabilization	0.309	We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.	SIGNOR-276262
P06493	P16949	1	phosphorylation	up-regulates activity	0.641	null	SIGNOR-279803
P00519	P23470	0	dephosphorylation	down-regulates activity	0.341	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254691
Q12778	Q9HCP0	0	phosphorylation	down-regulates activity	0.494	Phosphorylation of Ser319 forms a consensus sequence for phosphorylation by CK1, allowing it to phosphorylate Ser322, which in turn primes the CK1-catalysed phosphorylation of Ser325 \| Multisite phosphorylation of the region containing Ser319, Ser322, Ser325 and Ser329 provides a signal for the nuclear exclusion of FKHR	SIGNOR-250822
Q5TEC6	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-265415
P24941	O75533	1	phosphorylation	up-regulates	0.346	To map the set of phosphorylation sites in sap155-(223-322) that determine its interaction with nipp1, we have identified phosphorylation sites of cyclin e-cdk2 by the sequencing of proteolytically derived phosphopeptide). Three phosphorylation sites were identified as thr244, thr248, and thr313	SIGNOR-90434
P17252	Q9UQL6	1	phosphorylation	down-regulates activity	0.2	We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. \| Finally, we assessed the ability of PKD to phosphorylate HDAC5 in cells by employing an antibody that specifically recognizes HDAC5 that has been phosphorylated at serine 259. HDAC5 was basally phosphorylated at serine 259, and phosphorylation at this site was dramatically increased by coexpression of constitutively active PKD S/E	SIGNOR-249269
P60891	P50053	0	phosphorylation	up-regulates activity	0.348	Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development	SIGNOR-265735
O95747	Q96J92	0	phosphorylation	up-regulates activity	0.48	In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].\|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].	SIGNOR-278389
P06239	P03372	1	phosphorylation	up-regulates	0.382	On the basis of these data and other reports describing the structure and activity of y537 mutations, as well as knowledge of the three-dimensional structure of the her ligand binding domain, we propose an alternate model wherein y537f mutation favors an open pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active closed pocket conformation.	SIGNOR-55853
Q9H4B4	P15336	1	phosphorylation	up-regulates	0.2	Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.	SIGNOR-163274

P25963

P19525

0

phosphorylation

down-regulates quantity by destabilization

0.532

As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kappa B inhibitor I kappa B alpha at serine 32 before degradation.

SIGNOR-249335

P51114

Q13153

0

phosphorylation

up-regulates activity

0.271

Identification of Ser420 in FXR1 as a PAK1 Kinase Target. During zebrafish muscle development, FXR1 Ser420 phosphorylation is needed for protein function.

SIGNOR-273713

Q13541

Q9P1W9

0

phosphorylation

up-regulates activity

0.414

Further, PIM2 triggered phosphorylation of AKT and 4EBP1 (XREF_FIG) clearly demonstrating the activation of PI3K pathway.

SIGNOR-279091

P09936

P0CG48

1

cleavage

up-regulates quantity

0.864

These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains

SIGNOR-249693

P55087

P68400

0

phosphorylation

down-regulates activity

0.416

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

SIGNOR-250827

O00763

P54646

0

phosphorylation

down-regulates activity

0.649

The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK.

SIGNOR-250318

P23769

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.355

GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).

SIGNOR-276884

Q9UM73

P31939

1

phosphorylation

up-regulates activity

0.377

ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity. ATIC activity is enhanced in the presence of NPM-ALK in vitro.The ATIC activity is enhanced by NPM-ALK in HEK-293T-Rex cells.

SIGNOR-276171

Q16549

P67775

1

phosphorylation

up-regulates

0.2

This together with the rapid kinetics of pp1-pp2a activation following p38 activation suggests that pp1 and/or pp2a complexes are direct targets for p38-mediated phosphorylation

SIGNOR-105783

P07101

Q00535

0

phosphorylation

up-regulates activity

0.408

In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.

SIGNOR-279022

P17612

P01100

1

phosphorylation

up-regulates activity

0.518

Human c-Fos protein is phosphorylated in vitro by PKA. phosphorylation of Fos occurs at serine residue 362. Modification of the Fos protein by phosphorylation with PKA then allows it to act as a regulator of its own synthesis by downregulating fos gene expression at a transcriptional level

SIGNOR-250356

O15350

Q96J02

0

ubiquitination

down-regulates quantity by destabilization

0.566

Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells

SIGNOR-278699

P52945

P78527

0

phosphorylation

down-regulates quantity by destabilization

0.307

The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.

SIGNOR-225542

P46531

P78536

0

cleavage

up-regulates activity

0.739

... here we show that an additional processing event occurs in the extracellular part of the receptor, preceding cleavage by the gamma-secretase-like activity. Purification of the activity accounting for this cleavage in vitro shows that it is due to tace (tnfalpha-converting enzyme), a member of the adam (a disintegrin and metalloprotease domain) family of metalloproteases.

SIGNOR-78903

P31749

O14746

1

phosphorylation

up-regulates

0.732

Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins.

SIGNOR-67313

Q9NYY3

P04637

1

phosphorylation

up-regulates activity

0.592

Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop.

SIGNOR-278980

P35125

P63000

0

relocalization

up-regulates

0.338

In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.

SIGNOR-98938

Q13535

P09874

1

phosphorylation

down-regulates

0.357

Specifically, ATR binds to and phosphorylates PARP1 at Ser179 after the ionophore treatments.|These data suggest that the phosphorylation of S179 is necessary and sufficient for ATR inhibition of PARP1 PARylation activity.

SIGNOR-278506

Q6UB99

P51153

1

transcriptional regulation

up-regulates quantity by expression

0.2

Neurite growth-related genes such as Trkb, Bdnf, Gap43, Coronin 1B, and Rab13 are downregulated in ANKRD11-deficient neurons.

SIGNOR-266738

P53350

Q8IWB6

1

phosphorylation

down-regulates quantity by destabilization

0.354

We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.

SIGNOR-273529

Q13489

Q99558

1

ubiquitination

down-regulates

0.65

Ciap1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate nik for degradation.

SIGNOR-167298

P17252

Q13188

0

phosphorylation

up-regulates activity

0.2

Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.

SIGNOR-277176

O15550

P31276

1

transcriptional regulation

up-regulates quantity by expression

0.267

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260027

P37231

P25025

1

transcriptional regulation

up-regulates quantity by expression

0.264

EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE).

SIGNOR-271682

Q13131

P10636-2

1

phosphorylation

down-regulates activity

0.2

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275438

P31749

Q9BPZ7

1

phosphorylation

up-regulates activity

0.703

Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt.

SIGNOR-276932

Q4G163

Q9UQM7

0

phosphorylation

up-regulates activity

0.403

CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. | these results implicate the 192RSST motif of Emi2 as a critical molecular target of CaMKII during CSF release

SIGNOR-260907

P67809

Q7Z6E9

0

ubiquitination

down-regulates quantity by destabilization

0.317

RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1

SIGNOR-271773

Q15661

O75030

0

transcriptional regulation

up-regulates quantity by expression

0.2

The transcription of tryptase gene in human mast cells is regulated by mi transcription factor |Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A.

SIGNOR-251725

P28482

Q02548

1

phosphorylation

down-regulates activity

0.351

In this study, we demonstrated that PAX5 was phosphorylated by ERK1/2 in vitro and in vivo at serines 189 and 283. This phosphorylation attenuated the transcriptional repression of BLIMP1 by PAX5.

SIGNOR-269087

P06493

P18754

1

phosphorylation

up-regulates activity

0.504

We show here that Cdc2 kinase phosphorylates the serines located in or near the nuclear localization signal (NLS) of hum an RCC1, the nucleotide exchange factor for Ran. This phosphorylation is necessary for RCC1 to generate RanGTP on mitotic chromosomes in mammalian cells, which in turn is required for spindle assembly and chromosome segregation. However, when both S2 and S11 were simultaneously mutated to As, the resulting 6His-RCC1S2,11A failed to be phosphorylated, whereas all of the other double mutants were phosphorylated (Fig. 1C). As expected, mutating all four sites to As (the 6His-RCC1S2,11,387A-T274A) also blocked phosphorylation (Fig. 1C).

SIGNOR-262704

P28482

O75030

1

phosphorylation

down-regulates

0.705

The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73the results suggested that s1p reduced melanin synthesis via s1p(3) receptor-mediated erk and rsk-1 activation, and subsequent mitf dual phosphorylation and degradation.

SIGNOR-75030

Q13485

P01106

1

transcriptional regulation

down-regulates quantity by repression

0.64

Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter.

SIGNOR-251493

P24385

P03372

0

transcriptional regulation

up-regulates quantity by expression

0.754

Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1.

SIGNOR-135053

Q05397

P23470

0

dephosphorylation

up-regulates activity

0.243

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254719

P17302

P27361

0

phosphorylation

down-regulates activity

0.637

These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication.

SIGNOR-249466

Q15554

P55795

0

post transcriptional regulation

down-regulates quantity

0.332

During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels.

SIGNOR-266806

Q9NP97

P17612

0

phosphorylation

up-regulates

0.2

Our results show that km23-1 is required for camp-responsive element (cre) transcriptional activation by tgf_, with s73-km23-1 being required for the cre-dependent tgf_ stimulation of fibronectin (fn) transcription.

SIGNOR-200456

Q9NP77

P24928

1

dephosphorylation

up-regulates activity

0.855

Phosphorylation of serine-2 (S2) and serine-5 (S5) of the C-terminal domain (CTD) of RNA polymerase II (RNAP II) is a dynamic process that regulates the transcription cycle and coordinates recruitment of RNA processing factors. The Fcp1 CTD phosphatase catalyzes dephosphorylation of S2-P.| Depletion of Ssu72 impairs transcription in vitro

SIGNOR-248815

O75569

P19525

0

phosphorylation

up-regulates activity

0.796

In stressed cells, this activation occurs when PACT, a PKR-binding protein, is phosphorylated and activates PKR.

SIGNOR-280003

Q6P0Q8

P60484

1

phosphorylation

up-regulates

0.666

We further demonstrate that binding of pten to specific pdz domains diminishes its degradation rate and facilitates its phosphorylation by mast kinases. Our results suggest a regulatory role of pdz domain binding on pten function by controlling its stability and phosphorylation status.

SIGNOR-138051

P40763

P00519

0

phosphorylation

up-regulates activity

0.445

Previously, we showed that c-Abl and Arg promote phosphorylation of the STAT3 transcription factor (Y705) in a variety of cancer cell lines , .|Since c-Abl and Arg activate STAT3, we investigated whether c-Abl and Arg regulate NF-kappaB signaling.

SIGNOR-279675

Q9NQC7

Q12933

1

deubiquitination

down-regulates activity

0.677

Cyld also interacts directly with tumour-necrosis factor receptor (tnfr)-associated factor 2 (traf2), an adaptor molecule involved in by members of the family of tnf/nerve growth factor receptors. (articolo-abstract)

SIGNOR-117860

Q14155

P05129

0

phosphorylation

up-regulates

0.2

Pkc_ directly phosphorylates _pix at ser583 and indirectly at ser340 in cells. herefore, we propose that pkc_ positively modulates dopamine release through _2pix phosphorylation. The pkc_-_pix-cdc42/rac1 phosphorylation axis may provide a new therapeutic target for the treatment of parkinsonian syndrome

SIGNOR-205238

Q13547

P00519

0

phosphorylation

up-regulates activity

0.507

Despite the fact that HDAC1 was phosphorylated by co-expression with c-Abl, stabilization of HDAC1 by c-Abl was not affected by mutations in its sites phosphorylated by c-Abl.|c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity dependent manner.

SIGNOR-280169

P12270

P28482

0

phosphorylation

up-regulates

0.374

Tpr is phosphorylated by erk2 at four different sites. / because phosphorylation of tpr by activated erk stabilizes their interaction, we hypothesize that this phosphorylation is not part of a signal amplification cascade but rather positions activated erk to perform a continuing function in the nuclear pore.

SIGNOR-181022

O15111

P35222

1

phosphorylation

up-regulates quantity

0.485

Interestingly, while IKK2 negatively regulates beta-catenin stability similar to GSK3beta, IKK1 seems to increase beta-catenin protein level and downstream signal, such as cyclin D1 transcription.|These results suggested IKK1 may phosphorylate beta-catenin at different residues and protect it from ubiquitination mediated degradation.

SIGNOR-280230

P53350

O60566

1

phosphorylation

up-regulates

0.84

We identify s676 as a plk1-specific phosphorylation site on bubr1. These findings describe the first in vivo verified phosphorylation site for human bubr1, identify plk1 as the kinase responsible for causing the characteristic mitotic bubr1 upshift, and attribute a kt-specific function to the hyperphosphorylated form of bubr1 in the stabilization of kt-mt interactions.

SIGNOR-157646

P84022

Q9H6Z4

0

relocalization

down-regulates

0.389

Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner

SIGNOR-184608

P06239

Q9UHD2

1

phosphorylation

down-regulates activity

0.2

The Src family kinases (SFKs) Lck, Hck, and Fgr directly phosphorylate TBK1 at Tyr354/394, to prevent TBK1 dimerization and activation.

SIGNOR-276724

Q9Y4C1

O60674

0

phosphorylation

up-regulates activity

0.2

KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2 phosphorylates KDM3A at tyrosine 1101 residue.

SIGNOR-277884

Q14790

P27361

0

phosphorylation

down-regulates

0.717

We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity

SIGNOR-203480

P06493

P36956

1

phosphorylation

up-regulates

0.287

Cdk1/cyclin b-mediated phosphorylation stabilizes srebp1 during mitosis.

SIGNOR-148354

Q8TD19

Q92974

1

phosphorylation

up-regulates activity

0.2

The phosphorylation of ARHGEF2 by NEK9 is the key step of this process.

SIGNOR-279638

Q15349

P42345

0

phosphorylation

up-regulates activity

0.392

Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref

SIGNOR-279232

P0DTC2

P07858

0

cleavage

up-regulates activity

0.2

SARS-2-S can use both CatB/L as well as TMPRSS2 for priming in these cell lines.

SIGNOR-260738

Q96PM5

P50750

0

phosphorylation

down-regulates

0.46

We showed that cdk9 phosphorylates pirh2 on ser-211 and thr-217 residues through their physical interaction. Phosphorylation of pirh2 renders it inactive and may contribute to p53-inhibition of transcriptional elongation of the hiv-1 ltr.

SIGNOR-201923

P29350

P78314

1

dephosphorylation

down-regulates

0.57

Shp-1 dephosphorylates 3bp2 and potentially downregulates 3bp2-mediated t cell antigen receptor signaling

SIGNOR-146508

P68400

Q9Y365

1

phosphorylation

down-regulates

0.409

Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity

SIGNOR-155740

O60674

P20701

1

phosphorylation

up-regulates activity

0.268

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-254739

Q9UQD0

Q13555

0

phosphorylation

up-regulates activity

0.271

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

SIGNOR-275794

O95644

Q16539

0

phosphorylation

down-regulates

0.622

We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.

SIGNOR-74560

Q12802

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.744

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-260527

Q9UHC6

Q6ZVD7

0

transcriptional regulation

down-regulates quantity by repression

0.2

In this study we performed chromatin immunoprecipitation coupled to shotgun cloning to discover novel STOX1A target genes. Our results show that CNTNAP2, a member of the neurexin family, is directly downregulated by STOX1A.

SIGNOR-269065

Q13451

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.306

These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.

SIGNOR-264542

Q05655

P15941

1

phosphorylation

up-regulates

0.336

We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin

SIGNOR-115501

Q9Y572

Q8NB16

1

phosphorylation

up-regulates activity

0.753

MLKL comprises a four-helical bundle tethered to the pseudokinase domain, which contains an unusual pseudoactive site. Although the pseudokinase domain binds ATP, it is catalytically inactive and its essential nonenzymatic role in necroptotic signaling is induced by receptor-interacting serine-threonine kinase 3 (RIPK3)-mediated phosphorylation.[...]S345, S347, and T349 in the MLKL activation loop were phosphorylated by RIPK3 in in vitro kinase assays

SIGNOR-266427

P55036

O43255

0

polyubiquitination

down-regulates quantity by destabilization

0.432

S5a/Rpn10 is a ubiquitin (Ub)-binding protein that is a subunit of the 26S proteasome but also exists free in the cytosol. It binds poly-Ub chains through its two Ub-interacting motifs (UIMs). We discovered that, unlike typical substrates of Ub ligases (E3s), S5a can be ubiquitinated by all E3s tested including multimeric and monomeric Ring finger E3s (MuRF1, Siah2, Parkin, APC, and SCF(betaTRCP1)), the U-box E3, CHIP, and HECT domain E3s (E6AP and Nedd4) when assayed with UbcH5 or related Ub-conjugating enzymes.The short half-life of S5a presumably is because of the presence of the UIM domain and reflects the ubiquitination of free S5a by many E3s.

SIGNOR-272748

P32927

P29350

0

dephosphorylation

down-regulates

0.522

However, inhibition of shp2 binding to betac, did not prevent tyrosine phosphorylation of shp2. Interestingly, this same phosphopeptide served as a substrate for the tyrosine phosphatase activity of both shp1 and shp2.

SIGNOR-114597

P07947

P09086

1

phosphorylation

up-regulates activity

0.2

These data suggest that Yes1 is the TKI-sensitive kinase that can directly phosphorylate OCT2.

SIGNOR-279664

O14950

O75116

0

phosphorylation

up-regulates activity

0.598

In addition, an in vitro kinase assay with mixed recombinant GST-ROCK2 and MLC2 revealed that ROCK2 phosphorylated WT MLC2, but not MLC2 S15A mutant, indicating that it phosphorylates MLC2 at S15 in vitro (XREF_FIG).

SIGNOR-279103

Q9UNE7

Q15797

1

ubiquitination

down-regulates

0.328

These results suggest that chip can interact with the smad1/smad4 proteins and block bmp signal transduction through the ubiquitin-mediated degradation of smad proteins.

SIGNOR-120731

P14923

P06241

0

phosphorylation

up-regulates activity

0.561

Phosphorylation of plakoglobin by Fer and Fyn kinases decreases plakoglobin-desmoplakin interaction and increases plakoglobin-α-catenin association. Fyn mainly phosphorylated Tyr549 and that it phosphorylated Tyr133 with a much lower activity

SIGNOR-251176

Q8NBP7

Q8IXL6

0

phosphorylation

up-regulates activity

0.537

Herein, we report that Fam20C and Fam20A significantly eliminate the Furin-cleavage of PCSK9 (XREF_FIG, lanes 5, 6), thereby enhancing the pPCSK9 activity|Herein, we show that Fam20C phosphorylates PCSK9 at Serines 47, 666, 668 and 688.

SIGNOR-278935

Q6IQ55

Q99550

1

phosphorylation

down-regulates quantity

0.2

Additionally, in vivo ubiquitin assays showed that expression of either the kinase-dead TTBK2 or the MPP9-S629 and S636-2A mutant significantly decreased the ubiquitination level of MPP9.|Also, the S629A mutant almost abolished the phosphorylation of MPP9 by TTBK2 in the kinase assay in vitro, suggesting that S629 is the main site for MPP9 phosphorylation by TTBK2.

SIGNOR-278998

P46937

P35813

0

dephosphorylation

up-regulates activity

0.269

Although the authors show an in vitro kinase assay where PPM1A supposedly dephosphorylates YAP on Ser127, Fig. 4A lacks a positive control to ensure that PPM1A purified from cells is active.|The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration.

SIGNOR-276984

Q9HD43

P10912

1

dephosphorylation

down-regulates activity

0.295

Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR

SIGNOR-248802

Q15797

O15194

0

dephosphorylation

down-regulates activity

0.498

Smad proteins transduce bone morphogenetic protein (BMP) and transforming growth factor-beta (TGFbeta) signals upon phosphorylation of their C-terminal SXS motif by receptor kinases.|Phosphatases that dephosphorylate the linker region are therefore likely to play an integral part in the regulation of Smad activity. We reported previously that small C-terminal domain phosphatases 1, 2, and 3 (SCP1-3) dephosphorylate Smad1 C-terminal tail, thereby attenuating BMP signaling. |The linker region of Smad1 consists of four MAPK phosphorylation sites (Ser-187, Ser-195, Ser-206, and Ser-214)

SIGNOR-248314

P48730

P04637

1

phosphorylation

up-regulates

0.578

Here we show that the direct association between a p53 n-terminal peptide and mdm2 is disrupted by phosphorylation of the peptide on thr(18) but not by phosphorylation at other n-terminal sites, including ser(15) and ser(37). Thr(18) was phosphorylated in vitro by casein kinase (ck1).

SIGNOR-75889

P24941

P12272

1

phosphorylation

down-regulates

0.372

Phosphorylation at the cyclin-dependent kinases site (thr85) of parathyroid hormone-related protein negatively regulates its nuclear localization

SIGNOR-68548

P12931

P52735

1

phosphorylation

up-regulates activity

0.527

Since we find that Vav2 is necessary for cell spreading and Src activity is necessary for Vav2 activation of Rac and lamellipodia formation, our data suggest a model of Rac activation by integrins that depends on Src phosphorylation of Vav2.|We did not detect increased Rac activation when Vav2 was cotransfected with activated Src, although Vav2 tyrosine phosphorylation was increased (data not shown), indicating that endogenous Src activity is sufficient to fully activate Vav2.

SIGNOR-280138

P07202

Q06710

0

transcriptional regulation

up-regulates quantity by expression

0.399

TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8.

SIGNOR-267277

P36507

P67775

0

dephosphorylation

down-regulates

0.493

In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.

SIGNOR-166652

O14994

P27361

0

phosphorylation

up-regulates

0.2

A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.

SIGNOR-121402

P03372

P00533

0

phosphorylation

up-regulates

0.59

Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er

SIGNOR-115734

P11168

P52945

0

transcriptional regulation

up-regulates quantity by expression

0.522

In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.

SIGNOR-255540

P29353

P09619

0

phosphorylation

up-regulates

0.659

In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc.

SIGNOR-36906

Q16665

P01588

1

transcriptional regulation

up-regulates quantity by expression

0.643

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates hypoxia-inducible genes including the human erythropoietin (EPO) gene.

SIGNOR-253695

P28482

Q96RK0

1

phosphorylation

down-regulates

0.372

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3))[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3

SIGNOR-169875

P48729

O60346

1

phosphorylation

down-regulates quantity by destabilization

0.309

We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.

SIGNOR-276262

P06493

P16949

1

phosphorylation

up-regulates activity

0.641

null

SIGNOR-279803

P00519

P23470

0

dephosphorylation

down-regulates activity

0.341

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254691

Q12778

Q9HCP0

0

phosphorylation

down-regulates activity

0.494

Phosphorylation of Ser319 forms a consensus sequence for phosphorylation by CK1, allowing it to phosphorylate Ser322, which in turn primes the CK1-catalysed phosphorylation of Ser325 | Multisite phosphorylation of the region containing Ser319, Ser322, Ser325 and Ser329 provides a signal for the nuclear exclusion of FKHR

SIGNOR-250822

Q5TEC6

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-265415

P24941

O75533

1

phosphorylation

up-regulates

0.346

To map the set of phosphorylation sites in sap155-(223-322) that determine its interaction with nipp1, we have identified phosphorylation sites of cyclin e-cdk2 by the sequencing of proteolytically derived phosphopeptide). Three phosphorylation sites were identified as thr244, thr248, and thr313

SIGNOR-90434

P17252

Q9UQL6

1

phosphorylation

down-regulates activity

0.2

We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. | Finally, we assessed the ability of PKD to phosphorylate HDAC5 in cells by employing an antibody that specifically recognizes HDAC5 that has been phosphorylated at serine 259. HDAC5 was basally phosphorylated at serine 259, and phosphorylation at this site was dramatically increased by coexpression of constitutively active PKD S/E

SIGNOR-249269

P60891

P50053

0

phosphorylation

up-regulates activity

0.348

Ketohexokinase-A (KHK-A; also known as fructokinase-A) phosphorylates PRPS1 T225 and activates PRPS1 by blocking the binding of ADP, AMP, and GDP, which is required for hepatocellular carcinoma development

SIGNOR-265735

O95747

Q96J92

0

phosphorylation

up-regulates activity

0.48

In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].

SIGNOR-278389

P06239

P03372

1

phosphorylation

up-regulates

0.382

On the basis of these data and other reports describing the structure and activity of y537 mutations, as well as knowledge of the three-dimensional structure of the her ligand binding domain, we propose an alternate model wherein y537f mutation favors an open pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active closed pocket conformation.

SIGNOR-55853

Q9H4B4

P15336

1

phosphorylation

up-regulates

0.2

Phosphorylation of thr-69 by mapk14 and mapk11, and at thr-71 by mapk1/erk2, mapk3/erk1, mapk11, mapk12 and mapk14 in response to external stimulus like insulin causes increased transcriptional activity.

SIGNOR-163274