GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P09769	Q9UK17	1	phosphorylation	up-regulates activity	0.2	These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.	SIGNOR-276394
Q15796	O15194	0	dephosphorylation	down-regulates activity	0.498	Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248310
P11362	Q15118	1	phosphorylation	up-regulates	0.347	Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1	SIGNOR-193454
Q8IZP0	P60484	0	dephosphorylation	down-regulates quantity by destabilization	0.241	After dephosphorylation by PTEN, Abi1 is degraded by calpains.\|We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway.	SIGNOR-276948
P02533	P06850	0	transcriptional regulation	down-regulates quantity by repression	0.2	CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.	SIGNOR-251899
Q9UHD2	P12830	1	phosphorylation	down-regulates activity	0.272	Inhibition of TBK1 increases association of Cdh1 with APC1.\|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).	SIGNOR-278996
Q9NPH5	P06241	0	phosphorylation	down-regulates activity	0.271	We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation.	SIGNOR-277273
Q9Y222	P07996	1	transcriptional regulation	up-regulates quantity by expression	0.2	Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.	SIGNOR-261587
Q13237	P48764	1	phosphorylation	down-regulates activity	0.377	CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.\|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.	SIGNOR-280096
P49336	Q01094	1	phosphorylation	down-regulates	0.483	E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.	SIGNOR-181078
O76070	P25098	0	phosphorylation	down-regulates activity	0.2	GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2	SIGNOR-251204
Q14004	P24928	1	phosphorylation	up-regulates activity	0.541	Together, these studies demonstrate the important, yet largely redundant, role for CDK12 and CDK13 for the regulation of POLII CTD phosphorylation at multiple residues, as well as the global role for both of these kinases in regulating POLII occupancy across the genome.\|CDK12 and CDK13 are thus evolutionarily related and structurally similar kinases, and biochemical assays have demonstrated that both have POLII C-terminal domain (CTD) kinase activity and the ability to phosphorylate the Ser2 residue of the repetitive CTD heptad sequence	SIGNOR-273054
P38398	Q13535	0	phosphorylation	up-regulates activity	0.8	Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.	SIGNOR-106432
P28482	Q99814	1	phosphorylation	up-regulates quantity by stabilization	0.25	The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.	SIGNOR-277585
P17655	P10636	1	cleavage	down-regulates activity	0.433	Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains	SIGNOR-251611
Q15139	Q13563	1	phosphorylation	up-regulates activity	0.458	Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation.We confirmed previous studies showing that PC2 mediated Ca2+ release from the ER can be stimulated by ATP.Phosphorylation at Ser801 seems to be permissive for this activity without altering the subcellular localization nor homophilic and heterophilic (with PC1) interactions of wild-type PC2.	SIGNOR-259829
P06241	P51812	1	phosphorylation	up-regulates	0.326	Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.	SIGNOR-160048
Q8IWW6	P63000	1	gtpase-activating protein	down-regulates activity	0.546	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-260469
P43699	P07202	1	transcriptional regulation	up-regulates quantity by expression	0.379	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-267278
Q12888	P53350	0	phosphorylation	down-regulates activity	0.596	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|Addition of the inhibitors for PLK1 and the p38 MAPK leads to a complete loss of pT1609/pS1618 signal within 3 hr in mitotic cells	SIGNOR-264413
P30304	O96017	0	phosphorylation	down-regulates quantity by destabilization	0.843	We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.	SIGNOR-106808
P14598	P05771	0	phosphorylation	up-regulates	0.565	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89197
Q96JP5	Q99558	1	ubiquitination	up-regulates	0.5	Zfp91 interacts with and promotes the lys(63)-linked ubiquitination of nik and subsequent processing of p100 to p52.	SIGNOR-167331
Q92769	P29475	0	s-nitrosylation	down-regulates activity	0.265	we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation	SIGNOR-236919
P00533	Q14457	1	phosphorylation	down-regulates activity	0.521	The mechanism by which EGFR suppresses Beclin 1 function involves EGFR interaction with two domains (BH3 and ECD) of Beclin 1; EGFR mediated multisite tyrosine phosphorylation of Beclin 1 on residues Y229, Y233 and Y352; and EGFR mediated alterations in the Beclin 1 interactome (increased binding to the negative regulators, Bcl-2 and Rubicon, and decreased binding to the VPS34 lipid kinase).\|Thus, EGFR signaling suppresses autophagy via its interaction with Beclin 1 during normal mitogenic signaling as well as during aberrant cell proliferation in cancer cells.	SIGNOR-278357
Q9NRM7	P38936	1	phosphorylation	down-regulates quantity	0.417	Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis.\|Subsequently, Lats2 phosphorylates p21 at S146.	SIGNOR-279530
P15941	P00533	0	phosphorylation	up-regulates activity	0.577	We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells	SIGNOR-109538
Q14493	P16104	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265405
Q14653	P01574	1	transcriptional regulation	up-regulates quantity by expression	0.665	Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants	SIGNOR-252257
P06493	O95997	1	phosphorylation	up-regulates	0.598	Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation.	SIGNOR-74619
P11802	P43694	1	phosphorylation	up-regulates activity	0.356	In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).\|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.	SIGNOR-279148
Q86V86	Q92934	1	phosphorylation	down-regulates activity	0.346	Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.	SIGNOR-250399
P16284	P41240	0	phosphorylation	up-regulates activity	0.55	We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.	SIGNOR-262741
Q12888	Q13315	0	phosphorylation	up-regulates	0.873	Here we report phosphorylation of 53bp1 at several novel residues, using mass spectrometry and phospho-specific antibodies, and show that ionising radiation-stimulated phosphorylation of these residues requires atm.	SIGNOR-197615
Q15759	P00533	1	phosphorylation	down-regulates	0.334	P38 map kinase mediates stress-induced internalization of egfrthe underlying mechanism entails phosphorylation of egfr at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two rab5 effectors, eea1 and gdi.	SIGNOR-149086
Q96KS0	P45984	0	phosphorylation	up-regulates activity	0.2	Interestingly, we found that docetaxel induced JNK2 activation increased phosphorylation of PHD1 at Ser 74 and Ser 162 in hypoxic cancer cells (XREF_FIG).	SIGNOR-279077
Q9BUB5	P28482	0	phosphorylation	up-regulates	0.594	We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor-4e (eif-4e).	SIGNOR-48298
P13639	P67775	0	dephosphorylation	up-regulates	0.404	Protein phosphatases-2a and -2c (pp-2a and pp-2c) can each efficiently dephosphorylate phosphorylated eef-2	SIGNOR-38566
Q05209	P04626	1	dephosphorylation	down-regulates activity	0.619	In MDA-MB-231 cells, a human triple negative breast cancer cell line, phosphorylation of PTPN12 on Ser 19 was increased in response to cyclin dependent kinase 2 (CDK2), and this impaired PTPN12 's ability to dephosphorylate HER2 on Y1196.\|PTPN12 negatively regulates Her2, by dephosphorylation on Tyr 1196 on Her2.	SIGNOR-277038
Q14004	Q86VE9	1	phosphorylation	down-regulates quantity by destabilization	0.2	In addition, CDK13-KD disrupted Nef downregulation of SERINC5 from the cell surface, whereas CDK12-KD did not (Figures 2D and 2E).\|Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.\|Thus, we conclude that CycK/CDK13 phosphorylates the S360 residue of SERINC5.	SIGNOR-278918
Q63HK5	O00213	0	relocalization	up-regulates activity	0.366	We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.	SIGNOR-264813
P06127	P06239	0	phosphorylation	up-regulates activity	0.541	Tyrosine phosphorylation of cd5 requires lck activity. We propose that t cell activation mediates cd5 tyrosine phosphorylation at residues y429 and y463 mainly through the activation of lck	SIGNOR-106799
P60510	Q12888	1	dephosphorylation	up-regulates activity	0.357	Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.\|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks \|Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618	SIGNOR-264450
Q8WXX7	O15409	0	transcriptional regulation	up-regulates quantity by expression	0.325	By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.	SIGNOR-266832
P31749	Q12906	1	phosphorylation	up-regulates activity	0.367	Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.\|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.	SIGNOR-252512
P28482	P17655	1	phosphorylation	up-regulates	0.628	Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo.	SIGNOR-123079
P14921	Q13554	0	phosphorylation	down-regulates activity	0.309	Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites \| Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1	SIGNOR-250684
Q12974	P24941	1	dephosphorylation	up-regulates	0.2	Cells overexpressing prl-2 exhibited enhanced cyclin-dependent kinase 2 (cdk2) activity	SIGNOR-119478
Q9H4B4	Q14790	1	phosphorylation	up-regulates activity	0.338	Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.	SIGNOR-272995
P47712	P17252	0	phosphorylation	up-regulates	0.564	Pkcalfa, but not pkcbeta, is the predominant cpkc isoenzyme required for cpla2 protein phosphorylation and maximal induction of cpla2 enzymatic activity.	SIGNOR-149406
P55075	Q9BYU1	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265806
P42685	P46937	1	phosphorylation	down-regulates quantity by destabilization	0.275	Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.	SIGNOR-275456
Q08881	Q06124	0	dephosphorylation	down-regulates activity	0.324	Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions.	SIGNOR-277174
Q9NZQ7	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.307	We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP.	SIGNOR-277275
O14490	Q9UQM7	0	phosphorylation	down-regulates quantity by destabilization	0.397	CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP.	SIGNOR-276429
P35367	Q13976	0	phosphorylation	down-regulates	0.2	Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995	SIGNOR-66019
Q06187	P42768	1	phosphorylation	up-regulates activity	0.743	These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.	SIGNOR-273958
P07948	O75807	1	phosphorylation	up-regulates	0.334	Gadd34 was tyrosine-phosphorylated in vivo in a lyn-dependent manner.	SIGNOR-109934
Q00987	P46695	1	ubiquitination	down-regulates quantity by destabilization	0.349	FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.\|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.	SIGNOR-278824
P42771	P01106	0	transcriptional regulation	down-regulates quantity by repression	0.766	C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a	SIGNOR-102743
P12931	P05106	1	phosphorylation	down-regulates activity	0.661	The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength.	SIGNOR-247207
Q9Y446	P12931	0	phosphorylation	up-regulates activity	0.306	We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.	SIGNOR-273807
Q9H0K1	Q53ET0	1	phosphorylation	down-regulates	0.743	Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2	SIGNOR-142218
P17252	Q13131	1	phosphorylation	down-regulates activity	0.2	Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.	SIGNOR-276459
Q7Z2W7	P67775	0	dephosphorylation	down-regulates activity	0.2	Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.	SIGNOR-273793
Q9UBF8	Q15139	0	phosphorylation	up-regulates	0.405	Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity.	SIGNOR-148876
P53350	Q38SD2	1	phosphorylation	up-regulates activity	0.345	Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes	SIGNOR-275467
Q15797	P23771	1	transcriptional regulation	up-regulates quantity	0.291	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268938
Q16665	Q9Y3V2	0	sumoylation	up-regulates	0.457	Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia	SIGNOR-158590
Q9UQM7	P28329	1	phosphorylation	up-regulates	0.372	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-96628
P05129	P41594	1	phosphorylation	up-regulates activity	0.415	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249289
Q13153	P67775	0	dephosphorylation	down-regulates activity	0.357	Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.	SIGNOR-248641
P49137	Q9Y385	1	phosphorylation	down-regulates quantity by destabilization	0.334	Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFα production. These findings strongly suggest that MK2 directly phosphorylates Ube2j1 at Ser(184) upon p38-activating stress in vivo.	SIGNOR-263091
Q9NQX3	P49841	0	phosphorylation	down-regulates	0.283	Identification of gsk3_ as the kinase targeting ser-270 /phosphorylation at ser-270 promotes gephyrin processing by calpain	SIGNOR-200957
Q8NFU7	O15294	0	glycosylation	up-regulates activity	0.44	The DNA demethylation enzyme Tet1 interacts with Ogt and is O-GlcNAcylated. Tet1 protein stability is positively regulated by O-GlcNAcylation, and its repression function on targeting genes is dependent on Ogt.	SIGNOR-259184
Q01094	P27361	0	phosphorylation	up-regulates	0.292	Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1	SIGNOR-121991
O75385	Q13501	1	phosphorylation	down-regulates quantity by destabilization	0.567	ULK1 phosphorylates p62 at the Ser403 site.	SIGNOR-278349
P27361-3	P06493	0	phosphorylation	up-regulates activity	0.314	We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB).	SIGNOR-277185
P00519	P35637	1	phosphorylation	down-regulates activity	0.325	Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS.	SIGNOR-280168
P11362	P28482	0	phosphorylation	down-regulates	0.309	Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling	SIGNOR-200880
P19525	O75569	1	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
P07737	P61586	0	null	up-regulates activity	0.569	We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.\|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells.	SIGNOR-253109
P40763	Q15678	0	dephosphorylation	down-regulates activity	0.271	Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus.\|The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells.	SIGNOR-277088
Q16665	P98170	0	ubiquitination	up-regulates activity	0.284	HIF1alpha is ubiquitinated by XIAP.\|Lys 63 -linked ubiquitination of HIF1alpha by XIAP is dependent on the activity of E2 ubiquitin conjugating enzyme Ubc13.\|We find that XIAP and Ubc13 dependent Lys 63 -linked polyubiquitination promotes HIF1alpha nuclear retention leading to an increase in the expression of HIF1 responsive genes.\|The data indicate that XIAP promotes the formation of the non-degradative Lys63-linked ubiquitin chains onto hypoxia inducible factor1\u03b1, but does not affect the formation of Lys48-linked chains.	SIGNOR-278740
P14635	P50539	0	transcriptional regulation	down-regulates quantity by repression	0.266	Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression \| Mxi1 inhibits the promoter activity of the cyclin B1 gene.	SIGNOR-266064
P12931	O14757	0	phosphorylation	up-regulates activity	0.338	In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity.	SIGNOR-278332
Q8IWV8	Q9H410	1	ubiquitination	down-regulates quantity	0.2	Mub1 and Ubr2 mediate Dsn1 ubiquitylation and degradation.\|The levels of WT Dsn1 were also increased in the mub1Delta and ubr2Delta strains, suggesting that Mub1 and Ubr2 mediate the degradation of WT Dsn1 protein.	SIGNOR-278795
P38432	P24941	0	phosphorylation	up-regulates	0.381	In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed	SIGNOR-84949
Q5JU85	P42262	1	relocalization	up-regulates quantity	0.2	BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.	SIGNOR-264913
P62993	P35968	0	relocalization	up-regulates activity	0.686	In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.	SIGNOR-261948
P62136	Q00535	0	phosphorylation	down-regulates activity	0.395	Pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.	SIGNOR-92269
O60260	O43175	1	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin binds to PHGDH and degrades it through ubiquitination to inhibit serine synthesis, which contributes greatly to the tumor-suppressive function of Parkin.	SIGNOR-269075
Q9UNE7	P53350	1	ubiquitination	down-regulates quantity by destabilization	0.252	As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.\|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.	SIGNOR-278532
P01019	P24158	0	cleavage	up-regulates activity	0.259	Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.	SIGNOR-256314
Q9Y698	P17612	0	phosphorylation	down-regulates activity	0.432	phosphorylation of stargazin at T321 by PKA inhibits its interaction with PSD-95.	SIGNOR-250342
Q9NXR1	P28482	0	phosphorylation	up-regulates activity	0.374	Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro. In the case of Nudel, the phosphorylation sites were also located in the S/TP motifs. Detailed mutagenesis study indicated that T219, S242, and T245 were phosphorylated by Cdc2, while T219 and T245 were phosphorylated by Erk2.\|Phosphorylation of Nudel in M phase appears to positively modulate dynein motor activity. Both phosphorylated and unphosphorylated forms of Nudel were transported by dynein (Fig. 7 and 9 and data not shown), indicating that neither of them inactivated the dynein motor. On the other hand, both phospho-Nudel and Nudelpmt5 bound Lis1 more strongly than Nudel or Nudelmt5 did	SIGNOR-249422
Q9Y4K3	Q8IUC6	1	polyubiquitination	up-regulates	0.83	Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1	SIGNOR-271428
Q92831	P08151	1	acetylation	down-regulates activity	0.469	NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase	SIGNOR-269270
Q13418	Q13765	1	phosphorylation	up-regulates	0.426	Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.	SIGNOR-127694
P54646	O00418	1	phosphorylation	up-regulates activity	0.498	Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398. phosphorylation of eEF2 kinase at Ser-398 leads to an increase in its activity.	SIGNOR-250158

P09769

Q9UK17

1

phosphorylation

up-regulates activity

0.2

These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels.

SIGNOR-276394

Q15796

O15194

0

dephosphorylation

down-regulates activity

0.498

Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248310

P11362

Q15118

1

phosphorylation

up-regulates

0.347

Mitochondrial pdhk1 is tyrosine phosphorylated and activated by fgfr1 in cancer cells further mass spectrometric analysis identified three tyrosine residues of pdhk1, including y136, y243 and y244, that are phosphorylated by fgfr1

SIGNOR-193454

Q8IZP0

P60484

0

dephosphorylation

down-regulates quantity by destabilization

0.241

After dephosphorylation by PTEN, Abi1 is degraded by calpains.|We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway.

SIGNOR-276948

P02533

P06850

0

transcriptional regulation

down-regulates quantity by repression

0.2

CRH stimulated the expression of cytokeratin 1 and involucrin, and inhibited cytokeratin 14 on both mRNA and protein levels.

SIGNOR-251899

Q9UHD2

P12830

1

phosphorylation

down-regulates activity

0.272

Inhibition of TBK1 increases association of Cdh1 with APC1.|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).

SIGNOR-278996

Q9NPH5

P06241

0

phosphorylation

down-regulates activity

0.271

We found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation.

SIGNOR-277273

Q9Y222

P07996

1

transcriptional regulation

up-regulates quantity by expression

0.2

Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.

SIGNOR-261587

Q13237

P48764

1

phosphorylation

down-regulates activity

0.377

CGMP and cGKII increased NHE3 phosphorylation at three sites (rabbit Ser (554), Ser (607), and Ser (663), equivalent to mouse Ser (552), Ser (605), and Ser (659)), all of which had to be present at the same time for cGMP to inhibit NHE3.|cGMP and cGKII rapidly inhibited NHE3, which was associated with reduced surface NHE3.

SIGNOR-280096

P49336

Q01094

1

phosphorylation

down-regulates

0.483

E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein. Elevated levels of CDK8 protect beta-catenin/TCF-dependent transcription from inhibition by E2F1.

SIGNOR-181078

O76070

P25098

0

phosphorylation

down-regulates activity

0.2

GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser124 dramatically inhibits γ-synuclein phosphorylation by GRK2

SIGNOR-251204

Q14004

P24928

1

phosphorylation

up-regulates activity

0.541

Together, these studies demonstrate the important, yet largely redundant, role for CDK12 and CDK13 for the regulation of POLII CTD phosphorylation at multiple residues, as well as the global role for both of these kinases in regulating POLII occupancy across the genome.|CDK12 and CDK13 are thus evolutionarily related and structurally similar kinases, and biochemical assays have demonstrated that both have POLII C-terminal domain (CTD) kinase activity and the ability to phosphorylate the Ser2 residue of the repetitive CTD heptad sequence

SIGNOR-273054

P38398

Q13535

0

phosphorylation

up-regulates activity

0.8

Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.

SIGNOR-106432

P28482

Q99814

1

phosphorylation

up-regulates quantity by stabilization

0.25

The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33.Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells.

SIGNOR-277585

P17655

P10636

1

cleavage

down-regulates activity

0.433

Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains

SIGNOR-251611

Q15139

Q13563

1

phosphorylation

up-regulates activity

0.458

Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation.We confirmed previous studies showing that PC2 mediated Ca2+ release from the ER can be stimulated by ATP.Phosphorylation at Ser801 seems to be permissive for this activity without altering the subcellular localization nor homophilic and heterophilic (with PC1) interactions of wild-type PC2.

SIGNOR-259829

P06241

P51812

1

phosphorylation

up-regulates

0.326

Epidermal growth factor stimulates rsk2 activation through activation of the mek/erk pathway and src-dependent tyrosine phosphorylation of rsk2 at tyr-529. By mass spectroscopy-based studies, we identified src tyrosine kinase family members src and fyn as upstream kinases of rsk2 tyr-529.

SIGNOR-160048

Q8IWW6

P63000

1

gtpase-activating protein

down-regulates activity

0.546

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-260469

P43699

P07202

1

transcriptional regulation

up-regulates quantity by expression

0.379

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-267278

Q12888

P53350

0

phosphorylation

down-regulates activity

0.596

Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |Addition of the inhibitors for PLK1 and the p38 MAPK leads to a complete loss of pT1609/pS1618 signal within 3 hr in mitotic cells

SIGNOR-264413

P30304

O96017

0

phosphorylation

down-regulates quantity by destabilization

0.843

We show that IR-induced destruction of Cdc25A requires both ATM and the Chk2-mediated phosphorylation of Cdc25A on serine 123.

SIGNOR-106808

P14598

P05771

0

phosphorylation

up-regulates

0.565

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89197

Q96JP5

Q99558

1

ubiquitination

up-regulates

0.5

Zfp91 interacts with and promotes the lys(63)-linked ubiquitination of nik and subsequent processing of p100 to p52.

SIGNOR-167331

Q92769

P29475

0

s-nitrosylation

down-regulates activity

0.265

we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation

SIGNOR-236919

P00533

Q14457

1

phosphorylation

down-regulates activity

0.521

The mechanism by which EGFR suppresses Beclin 1 function involves EGFR interaction with two domains (BH3 and ECD) of Beclin 1; EGFR mediated multisite tyrosine phosphorylation of Beclin 1 on residues Y229, Y233 and Y352; and EGFR mediated alterations in the Beclin 1 interactome (increased binding to the negative regulators, Bcl-2 and Rubicon, and decreased binding to the VPS34 lipid kinase).|Thus, EGFR signaling suppresses autophagy via its interaction with Beclin 1 during normal mitogenic signaling as well as during aberrant cell proliferation in cancer cells.

SIGNOR-278357

Q9NRM7

P38936

1

phosphorylation

down-regulates quantity

0.417

Phosphorylation by Lats2 induces degradation of p21 and promotes apoptosis.|Subsequently, Lats2 phosphorylates p21 at S146.

SIGNOR-279530

P15941

P00533

0

phosphorylation

up-regulates activity

0.577

We also show that the activated egf-r phosphorylates the muc1 cytoplasmic tail on tyrosine at a yekv motif that functions as a binding site for the c-src sh2 domain. The results demonstrate that egf-r-mediated phosphorylation of muc1 induces binding of muc1 to c-src in cells

SIGNOR-109538

Q14493

P16104

1

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265405

Q14653

P01574

1

transcriptional regulation

up-regulates quantity by expression

0.665

Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants

SIGNOR-252257

P06493

O95997

1

phosphorylation

up-regulates

0.598

Hpttg is phosphorylated by cdc2 at ser165 these results suggest that hpttg is induced by, and may have a role in, regulatory pathways involved in the control of cell proliferation.

SIGNOR-74619

P11802

P43694

1

phosphorylation

up-regulates activity

0.356

In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.

SIGNOR-279148

Q86V86

Q92934

1

phosphorylation

down-regulates activity

0.346

Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.

SIGNOR-250399

P16284

P41240

0

phosphorylation

up-regulates activity

0.55

We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances.

SIGNOR-262741

Q12888

Q13315

0

phosphorylation

up-regulates

0.873

Here we report phosphorylation of 53bp1 at several novel residues, using mass spectrometry and phospho-specific antibodies, and show that ionising radiation-stimulated phosphorylation of these residues requires atm.

SIGNOR-197615

Q15759

P00533

1

phosphorylation

down-regulates

0.334

P38 map kinase mediates stress-induced internalization of egfrthe underlying mechanism entails phosphorylation of egfr at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two rab5 effectors, eea1 and gdi.

SIGNOR-149086

Q96KS0

P45984

0

phosphorylation

up-regulates activity

0.2

Interestingly, we found that docetaxel induced JNK2 activation increased phosphorylation of PHD1 at Ser 74 and Ser 162 in hypoxic cancer cells (XREF_FIG).

SIGNOR-279077

Q9BUB5

P28482

0

phosphorylation

up-regulates

0.594

We have identified a new subfamily of murine serine/threonine kinases, whose members, map kinase-interacting kinase 1 (mnk1) and mnk2, bind tightly to the growth factor-regulated map kinases, erk1 and erk2erk and p38 phosphorylate mnk1 and mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor-4e (eif-4e).

SIGNOR-48298

P13639

P67775

0

dephosphorylation

up-regulates

0.404

Protein phosphatases-2a and -2c (pp-2a and pp-2c) can each efficiently dephosphorylate phosphorylated eef-2

SIGNOR-38566

Q05209

P04626

1

dephosphorylation

down-regulates activity

0.619

In MDA-MB-231 cells, a human triple negative breast cancer cell line, phosphorylation of PTPN12 on Ser 19 was increased in response to cyclin dependent kinase 2 (CDK2), and this impaired PTPN12 's ability to dephosphorylate HER2 on Y1196.|PTPN12 negatively regulates Her2, by dephosphorylation on Tyr 1196 on Her2.

SIGNOR-277038

Q14004

Q86VE9

1

phosphorylation

down-regulates quantity by destabilization

0.2

In addition, CDK13-KD disrupted Nef downregulation of SERINC5 from the cell surface, whereas CDK12-KD did not (Figures 2D and 2E).|Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.|Thus, we conclude that CycK/CDK13 phosphorylates the S360 residue of SERINC5.

SIGNOR-278918

Q63HK5

O00213

0

relocalization

up-regulates activity

0.366

We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex.

SIGNOR-264813

P06127

P06239

0

phosphorylation

up-regulates activity

0.541

Tyrosine phosphorylation of cd5 requires lck activity. We propose that t cell activation mediates cd5 tyrosine phosphorylation at residues y429 and y463 mainly through the activation of lck

SIGNOR-106799

P60510

Q12888

1

dephosphorylation

up-regulates activity

0.357

Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |Depletion of PP4C, or PP4R3beta, causes persistence of phospho-T1609 and phospho-S1618

SIGNOR-264450

Q8WXX7

O15409

0

transcriptional regulation

up-regulates quantity by expression

0.325

By interacting with CASK, TBR1 regulates several ASD candidate genes, such as GRIN2B, AUTS2 and RELN—all of which are recurrently mutated in ASD. In areas of the brain with overlapping expression patterns, such as in glutamatergic layer 6 neurons, the TBR1–FOXP2 interaction may result in co-ordinated regulation of common downstream targets.

SIGNOR-266832

P31749

Q12906

1

phosphorylation

up-regulates activity

0.367

Upon T cell activation, NF90 translocates from the nucleus into the cytoplasm, where it binds to the AU-rich element-containing 3' untranslated regions of IL-2 mRNA and stabilizes it.|Our previous work showed that CD28 costimulation of T cells activated AKT to phosphorylate NF90 at Ser647 and caused NF90 to undergo nuclear export and stabilize IL-2 mRNA.

SIGNOR-252512

P28482

P17655

1

phosphorylation

up-regulates

0.628

Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo.

SIGNOR-123079

P14921

Q13554

0

phosphorylation

down-regulates activity

0.309

Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites | Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1

SIGNOR-250684

Q12974

P24941

1

dephosphorylation

up-regulates

0.2

Cells overexpressing prl-2 exhibited enhanced cyclin-dependent kinase 2 (cdk2) activity

SIGNOR-119478

Q9H4B4

Q14790

1

phosphorylation

up-regulates activity

0.338

Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function.

SIGNOR-272995

P47712

P17252

0

phosphorylation

up-regulates

0.564

Pkcalfa, but not pkcbeta, is the predominant cpkc isoenzyme required for cpla2 protein phosphorylation and maximal induction of cpla2 enzymatic activity.

SIGNOR-149406

P55075

Q9BYU1

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265806

P42685

P46937

1

phosphorylation

down-regulates quantity by destabilization

0.275

Mechanistically, FRK interacted with and phosphorylated YAP on Tyr391/407/444, which recruited the classical E3 ubiquitin ligase Siah1 to catalyze ubiquitination and eventually degradation of YAP.

SIGNOR-275456

Q08881

Q06124

0

dephosphorylation

down-regulates activity

0.324

Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions.

SIGNOR-277174

Q9NZQ7

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.307

We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP.

SIGNOR-277275

O14490

Q9UQM7

0

phosphorylation

down-regulates quantity by destabilization

0.397

CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP.

SIGNOR-276429

P35367

Q13976

0

phosphorylation

down-regulates

0.2

Ser396 and ser398 are also potential phosphorylation sites for capk, cgmp-dependent protein kinase, and camk ii. Elevation of intracellular camp content has been shown to attenuate histamine-induced accumulation of ip in c6 glioma cells (peakman and hill, 1994) and in ddt1 mf-2 smooth muscle cells (sipma et al., 1995

SIGNOR-66019

Q06187

P42768

1

phosphorylation

up-regulates activity

0.743

These results demonstrate that WASP, under this experimental condition, can be tyrosine-phosphorylated by the kinase activity of Btk and that the direct interaction between WASP and the SH3 domain of Btk is required for this phosphorylation to occur.

SIGNOR-273958

P07948

O75807

1

phosphorylation

up-regulates

0.334

Gadd34 was tyrosine-phosphorylated in vivo in a lyn-dependent manner.

SIGNOR-109934

Q00987

P46695

1

ubiquitination

down-regulates quantity by destabilization

0.349

FHL2 stimulates MDM2 mediated ubiquitination of IER3 by forming a ternary complex.|Scaffold protein FHL2 facilitates MDM2 mediated degradation of IER3 to regulate proliferation of cervical cancer cells.

SIGNOR-278824

P42771

P01106

0

transcriptional regulation

down-regulates quantity by repression

0.766

C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a

SIGNOR-102743

P12931

P05106

1

phosphorylation

down-regulates activity

0.661

The phosphorylation level of beta(3) integrin was modulated using a temperature-sensitive v-Src kinase. Increased beta(3) phosphorylation abolished alpha(v)beta(3)- but not alpha(5)beta(1)-mediated adhesion to fibronectin. Thus, phosphorylation of the cytoplasmic domain of beta(3) is a negative regulator of alpha(v)beta(3)-fibronectin binding strength.

SIGNOR-247207

Q9Y446

P12931

0

phosphorylation

up-regulates activity

0.306

We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.

SIGNOR-273807

Q9H0K1

Q53ET0

1

phosphorylation

down-regulates

0.743

Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2

SIGNOR-142218

P17252

Q13131

1

phosphorylation

down-regulates activity

0.2

Purified PKC and Akt both phosphorylated AMPKα1 Ser487 in vitro with similar efficiency. PKC activation was associated with reduced AMPK activity, as inhibition of PKC increased AMPK activity and phorbol esters inhibited AMPK, an effect lost in cells expressing mutant AMPKα1 Ser487Ala. Consistent with a pathophysiological role for this modification, AMPKα1 Ser487 phosphorylation was inversely correlated with insulin sensitivity in human muscle.

SIGNOR-276459

Q7Z2W7

P67775

0

dephosphorylation

down-regulates activity

0.2

Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.

SIGNOR-273793

Q9UBF8

Q15139

0

phosphorylation

up-regulates

0.405

Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity.

SIGNOR-148876

P53350

Q38SD2

1

phosphorylation

up-regulates activity

0.345

Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes

SIGNOR-275467

Q15797

P23771

1

transcriptional regulation

up-regulates quantity

0.291

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268938

Q16665

Q9Y3V2

0

sumoylation

up-regulates

0.457

Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia

SIGNOR-158590

Q9UQM7

P28329

1

phosphorylation

up-regulates

0.372

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.

SIGNOR-96628

P05129

P41594

1

phosphorylation

up-regulates activity

0.415

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249289

Q13153

P67775

0

dephosphorylation

down-regulates activity

0.357

Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.

SIGNOR-248641

P49137

Q9Y385

1

phosphorylation

down-regulates quantity by destabilization

0.334

Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFα production. These findings strongly suggest that MK2 directly phosphorylates Ube2j1 at Ser(184) upon p38-activating stress in vivo.

SIGNOR-263091

Q9NQX3

P49841

0

phosphorylation

down-regulates

0.283

Identification of gsk3_ as the kinase targeting ser-270 /phosphorylation at ser-270 promotes gephyrin processing by calpain

SIGNOR-200957

Q8NFU7

O15294

0

glycosylation

up-regulates activity

0.44

The DNA demethylation enzyme Tet1 interacts with Ogt and is O-GlcNAcylated. Tet1 protein stability is positively regulated by O-GlcNAcylation, and its repression function on targeting genes is dependent on Ogt.

SIGNOR-259184

Q01094

P27361

0

phosphorylation

up-regulates

0.292

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

SIGNOR-121991

O75385

Q13501

1

phosphorylation

down-regulates quantity by destabilization

0.567

ULK1 phosphorylates p62 at the Ser403 site.

SIGNOR-278349

P27361-3

P06493

0

phosphorylation

up-regulates activity

0.314

We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB).

SIGNOR-277185

P00519

P35637

1

phosphorylation

down-regulates activity

0.325

Abl kinase-mediated FUS Tyr526 phosphorylation alters nucleocytoplasmic FUS localization in FTLD-FUS.

SIGNOR-280168

P11362

P28482

0

phosphorylation

down-regulates

0.309

Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling

SIGNOR-200880

P19525

O75569

1

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

P07737

P61586

0

null

up-regulates activity

0.569

We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells.

SIGNOR-253109

P40763

Q15678

0

dephosphorylation

down-regulates activity

0.271

Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus.|The tyrosine phosphatase PTPN14 inhibits the activation of STAT3 in PEDV infected Vero cells.

SIGNOR-277088

Q16665

P98170

0

ubiquitination

up-regulates activity

0.284

HIF1alpha is ubiquitinated by XIAP.|Lys 63 -linked ubiquitination of HIF1alpha by XIAP is dependent on the activity of E2 ubiquitin conjugating enzyme Ubc13.|We find that XIAP and Ubc13 dependent Lys 63 -linked polyubiquitination promotes HIF1alpha nuclear retention leading to an increase in the expression of HIF1 responsive genes.|The data indicate that XIAP promotes the formation of the non-degradative Lys63-linked ubiquitin chains onto hypoxia inducible factor1\u03b1, but does not affect the formation of Lys48-linked chains.

SIGNOR-278740

P14635

P50539

0

transcriptional regulation

down-regulates quantity by repression

0.266

Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression | Mxi1 inhibits the promoter activity of the cyclin B1 gene.

SIGNOR-266064

P12931

O14757

0

phosphorylation

up-regulates activity

0.338

In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity.

SIGNOR-278332

Q8IWV8

Q9H410

1

ubiquitination

down-regulates quantity

0.2

Mub1 and Ubr2 mediate Dsn1 ubiquitylation and degradation.|The levels of WT Dsn1 were also increased in the mub1Delta and ubr2Delta strains, suggesting that Mub1 and Ubr2 mediate the degradation of WT Dsn1 protein.

SIGNOR-278795

P38432

P24941

0

phosphorylation

up-regulates

0.381

In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed

SIGNOR-84949

Q5JU85

P42262

1

relocalization

up-regulates quantity

0.2

BRAG1 increases the synaptic recycling pool of AMPARs.these data suggest that the BRAG1 enhancement of AMPAR transmission is mediated by the increased expression of the recycling pool of synaptic GluA2/3 receptors.

SIGNOR-264913

P62993

P35968

0

relocalization

up-regulates activity

0.686

In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function.

SIGNOR-261948

P62136

Q00535

0

phosphorylation

down-regulates activity

0.395

Pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.

SIGNOR-92269

O60260

O43175

1

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin binds to PHGDH and degrades it through ubiquitination to inhibit serine synthesis, which contributes greatly to the tumor-suppressive function of Parkin.

SIGNOR-269075

Q9UNE7

P53350

1

ubiquitination

down-regulates quantity by destabilization

0.252

As indicated in xref , all three Plk1 fragments were ubiquitinated by CHIP, suggesting that CHIP targets multiple sites of Plk1 for ubiquitination.|Mechanistically, CHIP mediated degradation of AR and Plk1 leads to enhanced efficacy of HSP90 inhibitors.

SIGNOR-278532

P01019

P24158

0

cleavage

up-regulates activity

0.259

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.

SIGNOR-256314

Q9Y698

P17612

0

phosphorylation

down-regulates activity

0.432

phosphorylation of stargazin at T321 by PKA inhibits its interaction with PSD-95.

SIGNOR-250342

Q9NXR1

P28482

0

phosphorylation

up-regulates activity

0.374

Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro. In the case of Nudel, the phosphorylation sites were also located in the S/TP motifs. Detailed mutagenesis study indicated that T219, S242, and T245 were phosphorylated by Cdc2, while T219 and T245 were phosphorylated by Erk2.|Phosphorylation of Nudel in M phase appears to positively modulate dynein motor activity. Both phosphorylated and unphosphorylated forms of Nudel were transported by dynein (Fig. 7 and 9 and data not shown), indicating that neither of them inactivated the dynein motor. On the other hand, both phospho-Nudel and Nudelpmt5 bound Lis1 more strongly than Nudel or Nudelmt5 did

SIGNOR-249422

Q9Y4K3

Q8IUC6

1

polyubiquitination

up-regulates

0.83

Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1

SIGNOR-271428

Q92831

P08151

1

acetylation

down-regulates activity

0.469

NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase

SIGNOR-269270

Q13418

Q13765

1

phosphorylation

up-regulates

0.426

Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.

SIGNOR-127694

P54646

O00418

1

phosphorylation

up-regulates activity

0.498

Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398. phosphorylation of eEF2 kinase at Ser-398 leads to an increase in its activity.

SIGNOR-250158