GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q05655	Q9H257	1	phosphorylation	up-regulates activity	0.432	Here we demonstrated that protein kinase C-delta (PKCdelta) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9 and Bcl10 complex assembly and canonical NF-kappaB control.	SIGNOR-278383
P29350	O60674	1	dephosphorylation	down-regulates activity	0.729	Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1	SIGNOR-248466
P11171	Q12959	1	relocalization	up-regulates activity	0.472	Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.	SIGNOR-266011
Q6PKG0	P24941	0	phosphorylation	up-regulates activity	0.2	CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.	SIGNOR-279015
Q86WV6	O75385	0	phosphorylation	down-regulates activity	0.2	Collectively, our data indicates that cGAS is essential for the activation of AMPK and ULK1 suppression of STING (XREF_FIG) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity (XREF_FIG).\|Collectively, our data indicates that cGAS is essential for the activation of AMPK/ULK1 suppression of STING ( xref ) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity ( xref ).	SIGNOR-279316
P37840	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei\|2. Parkin-associated endothelin receptor-like receptor (Pael-R).	SIGNOR-249705
Q7KZI7	Q13470	1	phosphorylation	down-regulates activity	0.2	We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.	SIGNOR-273867
P07737	P62136	0	dephosphorylation	up-regulates	0.247	Knockdown of the catalytic subunit of pp1 (pp1c_), but not pp2a (pp2ac_), increased ps137-pfn1 levels. Pp1c_ binds pfn1 in cultured cells, and this interaction was increased by a phosphomimetic mutation of pfn1 at ser-137 (s137d). Together, these data define pp1 as the principal phosphatase for ser-137 of pfn1	SIGNOR-196816
P12931	Q9NR80	1	phosphorylation	up-regulates	0.312	This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.	SIGNOR-179601
P11021	Q99941	0	transcriptional regulation	up-regulates quantity by expression	0.448	Accordingly, N-terminal fragments of each ATF6 isoform (N-ATF6α and N-ATF6β) were overexpressed in HeLa cells and the effects on GRP78 induction were assessed. When expressed at similar levels, N-ATF6α conferred ∼200-fold greater GRP78 promoter activation than N-ATF6β.	SIGNOR-261566
P11171	Q14980	1	relocalization	up-regulates activity	0.533	These results indicate that 4.1 proteins recruit NuMA and dynein to the anaphase cell cortex through their conserved CTD (Figure 2I).	SIGNOR-266012
Q2M1Z3	P49840	0	phosphorylation	up-regulates activity	0.337	We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.	SIGNOR-262878
Q96B36	P42345	0	phosphorylation	down-regulates activity	0.904	We propose that after mtorc1 kinase activation by upstream regulators, pras40 is phosphorylated directly by mtor, thus contributing to the relief of pras40-mediated substrate competitionwe also find that mutation of ser-221 to ala increases the inhibitory activity of pras40 toward mtorc1.	SIGNOR-178128
P30411	P35626	0	phosphorylation	down-regulates activity	0.2	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251462
P11166	P04637	0	transcriptional regulation	down-regulates quantity by repression	0.597	P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.	SIGNOR-267464
O14737	O14829	0	dephosphorylation	down-regulates quantity by destabilization	0.349	Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.\|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.	SIGNOR-277008
P53350	P24941	0	phosphorylation	up-regulates activity	0.375	Thus, CycA2-CDK2 can stimulate phosphorylation of PLK1 T210 in vitro and the interactions required for CycA2-mediated PLK1 T210 phosphorylation are detected in the cytoplasm, but not in the nucleus.\|We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1.	SIGNOR-280212
Q15750	O95147	0	dephosphorylation	down-regulates activity	0.298	DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells.	SIGNOR-277147
Q14940	P68400	0	phosphorylation	down-regulates activity	0.2	CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis	SIGNOR-276250
Q6ZMU5	Q05397	1	ubiquitination	down-regulates quantity by destabilization	0.326	Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination.	SIGNOR-278648
P49840	Q07820	1	phosphorylation	down-regulates quantity by destabilization	0.457	MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1. threonine 163, which represents the GSK-3 priming phosphorylation in this protein	SIGNOR-251217
Q13164	P51812	1	phosphorylation	up-regulates activity	0.561	This suggested that ERK5 may directly activate RSKs.\|In vitro active ERK5 also phosphorylated RSK2 that had been immunoprecipitated from transfected cells using an anti-HA antibody ( Fig. 2 B).\|Phosphorylation of RSK2 by ERK5 in vitro increased its activity towards GST-S6 as much as 8-fold (Figs. 2 C and E).	SIGNOR-279216
P63104	P53779	0	phosphorylation	down-regulates	0.2	Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190	SIGNOR-124009
P25098	Q14940	1	phosphorylation	down-regulates activity	0.2	Simultaneous mutation of five Ser/Thr residues within 702-714 to Ala ((702)ST/AA(714)) abolished phosphorylation and binding of beta-arrestin2. In transfected cells, the CK2 catalytic alpha subunit formed a complex with NHE5 and decreased wild-type but not (702)ST/AA(714) NHE5 activity, further supporting a regulatory role for this kinase. The rate of internalization of (702)ST/AA(714) was also diminished and relatively insensitive to overexpression of beta-arrestin2.	SIGNOR-275503
P35222	P17612	0	phosphorylation	up-regulates activity	0.478	Although pka did not affect the formation of a complex between glycogen synthase kinase 3beta (gsk-3beta), beta-catenin, and axin, phosphorylation of beta-catenin by pka inhibited ubiquitination of beta-catenin in intact cells and in vitro.	SIGNOR-140902
Q12888	Q9NS91	0	ubiquitination	up-regulates activity	0.611	RAD18 associates with 53BP1 and is recruited to DSB sites in a 53BP1 dependent manner specifically during G1-phase, RAD18 monoubiquitinates KBD domain of 53BP1 at lysine 1268 in vitro.\|These results suggest that RAD18 directed modification at Lysine 1268 of 53BP1 promotes the retention of 53BP1 at DSBs.	SIGNOR-278593
Q13131	P08151	1	phosphorylation	down-regulates activity	0.334	AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.	SIGNOR-259862
P49715	P06702	1	transcriptional regulation	up-regulates quantity by expression	0.227	Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.\|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells.	SIGNOR-254041
P54725	Q05086	0	polyubiquitination	down-regulates quantity by destabilization	0.486	Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.	SIGNOR-272550
P05129	P61764	1	phosphorylation	down-regulates activity	0.386	Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.	SIGNOR-249187
Q9BXH1	Q92570	0	transcriptional regulation	up-regulates quantity by expression	0.2	Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax.	SIGNOR-259396
P23443	P27708	1	phosphorylation	up-regulates activity	0.372	CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.	SIGNOR-267443
Q8N163	P68400	0	phosphorylation	up-regulates activity	0.2	CK2alphawas bound to DBC1 and phosphorylated DBC1. The phosphorylation of DBC1 by CK2alphawas evidenced by co-immunoprecipitation of CK2alphaand DBC1 in a GST pull-down assay, an in vitro kinase assay, and immunofluorescence staining. \|In our results, CK2alpha affected the\|These results suggest that DBC1 may be involved in the progression of gastric carcinoma by inducing the EMT and that it is closely associated with CK2alpha-mediated phosphorylation of DBC1. phosphorylation of Thr454 on DBC1	SIGNOR-267666
P53350	Q96GD4	0	phosphorylation	up-regulates activity	0.599	Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis.\|Thus, we conclude that Aurora B indirectly promotes the phosphorylation of MCAK on Ser715 at the kinetochores through phosphorylation of PLK1 at Thr210 and its ensuing activation.	SIGNOR-279358
Q9UKM9	Q99873	1	post transcriptional regulation	up-regulates quantity	0.247	RALY binds poly-U rich elements within several RNAs and regulates the expression as well as the stability of specific transcripts. Here we show that RALY binds PRMT1 mRNA and regulates its expression.\|We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels	SIGNOR-262273
Q06124	Q16620	1	dephosphorylation	down-regulates activity	0.707	Conversely, PTPN11 knockdown lead to increased Y 515 phosphorylation of TrkB compared to the scramble control in the neuronal cells.\|This study established that TrkB activation as demonstrated by receptor phosphorylation at Tyr 515 in the SH-SY5Y cells is negatively regulated by PTPN11 actions.	SIGNOR-277123
Q15208	Q13043	0	phosphorylation	up-regulates activity	0.332	Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.\|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity.	SIGNOR-279641
A6ND36	P36894	0	phosphorylation	up-regulates activity	0.374	These results indicate that ALK3 phosphorylates PAWS1 predominantly at Ser610 but can also phosphorylate at Ser614 and Ser616 in vitro. \|Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway.	SIGNOR-264766
Q13131	Q9Y478	1	phosphorylation	up-regulates	0.925	Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp	SIGNOR-157553
Q92949	Q5JVL4	1	transcriptional regulation	up-regulates quantity by expression	0.356	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266934
P11413	Q9NXA8	0	catalytic activity	up-regulates activity	0.278	Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.	SIGNOR-261211
P12931	P11511	1	phosphorylation	up-regulates	0.35	Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.	SIGNOR-186284
P42574	P49810	1	cleavage	up-regulates activity	0.405	In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329.	SIGNOR-261743
P49716	P48436	0	transcriptional regulation	down-regulates quantity by repression	0.272	Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation	SIGNOR-184283
O75496	O14965	0	phosphorylation	up-regulates activity	0.51	Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.\|Thr25 of geminin is phosphorylated by Aurora-A.	SIGNOR-278509
Q9ULU4	P15692	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262041
Q92630	P05412	1	phosphorylation	down-regulates	0.256	Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro	SIGNOR-195771
Q09472	P31751	0	phosphorylation	up-regulates	0.327	We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity	SIGNOR-148987
Q07954	P17612	0	phosphorylation	up-regulates activity	0.324	LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis.	SIGNOR-250000
Q07817	O14920	0	phosphorylation	down-regulates quantity	0.339	We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.\|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .	SIGNOR-279529
Q12923	Q15654	1	dephosphorylation	down-regulates activity	0.434	PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.\|Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells.	SIGNOR-248713
P24071	P49841	0	phosphorylation	down-regulates activity	0.2	GSK-3 is constitutively active in the absence of cytokine stimulation and can phosphorylate S263, keeping FcalphaRI in the inactive state.	SIGNOR-264857
P27361	P07101	1	phosphorylation	up-regulates	0.482	In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11	SIGNOR-34678
P46531	Q9NWT6	0	hydroxylation	down-regulates	0.55	We show that fih-1 hydroxylates notch icd at two residues (n(1945) and n(2012)) that are critical for the function of notch icd as a transactivator within cells and during neurogenesis and myogenesis in vivo. Fih-1 negatively regulates notch activity and accelerates myogenic differentiation.	SIGNOR-161057
P35968	P23470	0	dephosphorylation	down-regulates activity	0.253	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-254707
P00533	P21860	1	phosphorylation	up-regulates	0.67	The erbb3 protein which possesses little or no intrinsic protein tyrosine kinase activiity is phosphorylated by the activated egf receptor protein tyrosine kinase on tyrosine residues within the yxxm sequence motif. These phosphorylated tyrosine residues interact with the p85 regulatory subunit of pi 3-kinase, which could result in the activation of the p110 catalytic subunit via a conformational mechanism.	SIGNOR-34748
Q01860	Q6U7Q0	0	transcriptional regulation	up-regulates quantity by expression	0.2	Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.	SIGNOR-264900
Q8IYW5	P16403	1	polyubiquitination	down-regulates	0.2	ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46.	SIGNOR-272927
O14920	P20749	1	phosphorylation	up-regulates activity	0.365	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277364
Q15046	P27361	0	phosphorylation	up-regulates	0.2	Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.	SIGNOR-186125
Q9UM73	P49841	1	phosphorylation	up-regulates activity	0.248	It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.\|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells.	SIGNOR-280180
Q96RU2	Q13315	0	phosphorylation	up-regulates activity	0.311	These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.	SIGNOR-279007
Q99638	O14757	0	phosphorylation	up-regulates activity	0.669	Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.\|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation.	SIGNOR-279503
P49841	Q16566	0	phosphorylation	down-regulates activity	0.263	CAMK4 phosphorylates GSK3\u03b2 at serine 9, which leads to its inactivation. xref Accordingly, we examined the levels of phosphorylated GSK3\u03b2 at serine 9 (pGSK3\u03b2-ser9) in podocytes exposed to IgG from TG patients and calculated the ratio of pGSK3\u03b2-ser9 to total GSK3\u03b2.	SIGNOR-279142
P35580	Q14814	0	transcriptional regulation	up-regulates quantity by expression	0.322	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238766
Q8NC42	P15056	1	polyubiquitination	down-regulates quantity by destabilization	0.337	We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.	SIGNOR-272043
P19784	Q9NQB0	1	phosphorylation	up-regulates activity	0.378	We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. \| Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.	SIGNOR-251044
Q8WWK9	P06493	0	phosphorylation	up-regulates	0.288	Among these, thr-622 was specifically phosphorylated by cdk1-cyclin b1 both in vitro and in vivo. these findings suggest that cdk1-cyclin b1-mediated phosphorylation of tmap is important for and contributes to proper regulation of microtubule dynamics and establishment of functional bipolar spindles during mitosis.	SIGNOR-185317
Q9UKB1	P25963	1	ubiquitination	down-regulates	0.542	We report here the identification of an ikappab-ubiquitin (ub) ligase complex containing the f-box/wd40-repeat protein, beta-trcp, a vertebrate homolog of drosophila slimb. beta-trcp binds to ikappabalpha only when the latter is specifically phosphorylated by an ikappab kinase complex. here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of i kappa b alpha.	SIGNOR-64317
Q13315	Q00987	1	phosphorylation	down-regulates activity	0.756	Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation.	SIGNOR-94268
P19174	Q92830	0	acetylation	down-regulates activity	0.2	The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.	SIGNOR-275498
P28482	P19438	1	phosphorylation	down-regulates activity	0.5	Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation.\|Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a	SIGNOR-249453
Q9UN19	Q06187	0	phosphorylation	up-regulates activity	0.672	We present a number of lines of evidence that in vivo, Src-type tyrosine kinases are responsible for the phosphorylation of tyrosine 139 in DAPP-1. \| Although Btk appears to phosphorylate DAPP-1 relatively efficiently both in Sf9 cells and in vitro, we find no evidence that in either B cells or PAE cells Btk family kinases phosphorylate DAPP-1.	SIGNOR-250602
Q9Y6R4	P46734	1	phosphorylation	up-regulates activity	0.639	These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1.	SIGNOR-50891
Q9P289	Q8TDY4	1	phosphorylation	up-regulates activity	0.2	Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545\|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.	SIGNOR-272238
P29350	P15498	1	dephosphorylation	down-regulates activity	0.576	SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.	SIGNOR-277171
Q13188	P18754	1	phosphorylation	up-regulates	0.2	MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets.	SIGNOR-263146
P00734	P08709	1	null	up-regulates activity	0.301	Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind	SIGNOR-263529
P19174	P07948	0	phosphorylation	up-regulates activity	0.656	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249381
P17612	P17655	1	phosphorylation	down-regulates	0.262	Activation of m-calpain (calpain ii) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain.These Data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by pka.	SIGNOR-116248
Q9BQA1	P11802	0	phosphorylation	up-regulates activity	0.7	Phosphorylation of MEP50 on Thr 5 by D1T286A and CDK4 is necessary and sufficient to increase the intrinsic methyltransferase activity of PRMT5, resulting in increased H4R3 and H3R8 methylation and repression of the CUL4A/B expression.	SIGNOR-279019
P60953	Q8WZ64	0	gtpase-activating protein	down-regulates activity	0.495	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-260455
O60610	P55283	1	null	up-regulates activity	0.2	Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.	SIGNOR-253110
Q9C0B5	P21453	1	palmitoylation	up-regulates activity	0.2	We propose that DHHC5-mediated palmitoylation of S1P1R determines Gi coupling and its signalling in a spatio/temporal manner.	SIGNOR-261140
P29474	P41743	0	phosphorylation	down-regulates activity	0.2	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251635
O14867	Q9BYM8	0	ubiquitination	down-regulates quantity by destabilization	0.345	HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.	SIGNOR-236971
Q05655	P07948	0	phosphorylation	down-regulates activity	0.557	Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro	SIGNOR-251407
Q13224	P05129	0	phosphorylation	up-regulates activity	0.399	These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels.	SIGNOR-249085
P33076	P28482	0	phosphorylation	up-regulates	0.432	We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.	SIGNOR-160609
O43150	P62330	1	gtpase-activating protein	up-regulates activity	0.668	Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.	SIGNOR-269706
P18031	P51692	1	dephosphorylation	down-regulates activity	0.676	A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b	SIGNOR-248429
P60484	Q05397	1	dephosphorylation	down-regulates activity	0.821	The tumor suppressor PTEN is a phosphatase with sequence homology to tensin. PTEN dephosphorylates phosphatidylinositol 3,4, 5-trisphosphate (PIP3) and focal adhesion kinase (FAK), and it can inhibit cell growth, invasion, migration, and focal adhesions. We investigated molecular interactions of PTEN and FAK in glioblastoma and breast cancer cells lacking PTEN. The PTEN trapping mutant D92A bound wild-type FAK, requiring FAK autophosphorylation site Tyr397	SIGNOR-248547
P14210	Q02447	0	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.	SIGNOR-251741
P49840	O75444	1	phosphorylation	up-regulates	0.2	We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.	SIGNOR-159358
P11362	Q9P0J1	1	phosphorylation	down-regulates activity	0.292	Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients.	SIGNOR-276640
P16104	Q9H4B4	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.\|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.\|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.	SIGNOR-280073
P08069	P12004	1	phosphorylation	up-regulates activity	0.2	In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination.	SIGNOR-277252
Q9NXR1	P06493	0	phosphorylation	up-regulates activity	0.654	We found that Nudel and NudE were also phosphorylated in M phase (Fig. (Fig.22 and and3).3). First, Nudel and NudE were specifically phosphorylated in M phase. Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro.Due to conservation of the S/TP motifs, NudE may also be phosphorylated at similar sites by these kinases, though it contains an additional potential Cdk site at S282 (SPNR).	SIGNOR-274077
Q8WV44	Q02156	1	polyubiquitination	down-regulates quantity by destabilization	0.2	RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear.	SIGNOR-271668
P17676	P17174	1	transcriptional regulation	up-regulates quantity by expression	0.2	In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues	SIGNOR-254051

Q05655

Q9H257

1

phosphorylation

up-regulates activity

0.432

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

SIGNOR-278383

P29350

O60674

1

dephosphorylation

down-regulates activity

0.729

Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1

SIGNOR-248466

P11171

Q12959

1

relocalization

up-regulates activity

0.472

Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.

SIGNOR-266011

Q6PKG0

P24941

0

phosphorylation

up-regulates activity

0.2

CDK2 phosphorylates LARP1 protein, regulates TOP-protein expression and LARP1\u2019s translational activity.

SIGNOR-279015

Q86WV6

O75385

0

phosphorylation

down-regulates activity

0.2

Collectively, our data indicates that cGAS is essential for the activation of AMPK and ULK1 suppression of STING (XREF_FIG) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity (XREF_FIG).|Collectively, our data indicates that cGAS is essential for the activation of AMPK/ULK1 suppression of STING ( xref ) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity ( xref ).

SIGNOR-279316

P37840

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin is a protein of 465 amino acids, and its structure includes a ubiquitin homologous domain in its N terminus and two RING finger domains in its C terminus. Molecular studies have determined that parkin is an E3 ubiquitin ligase function, implicating parkin in the ubiquitin-proteasome system, and raising the possibility that mutations in the gene lead to loss or diminished function. Three substrates for the ubiquitin-ligase function of parkin have been identified to date.1. A 22kDa glycosolated form of alpha-synuclei|2. Parkin-associated endothelin receptor-like receptor (Pael-R).

SIGNOR-249705

Q7KZI7

Q13470

1

phosphorylation

down-regulates activity

0.2

We also discover a MARK-mediated phosphorylation on TNK1 at S502 that promotes an interaction between TNK1 and 14-3-3, which sequesters TNK1 and inhibits its kinase activity.Phosphorylation of TNK1 at S502 within the proline rich domain is required for TNK1 binding to 14-3-3.MARKs mediate phosphorylation at S502 and 14-3-3 binding to TNK1, which restrains the movement of TNK1 into heavy membrane-associated clusters.

SIGNOR-273867

P07737

P62136

0

dephosphorylation

up-regulates

0.247

Knockdown of the catalytic subunit of pp1 (pp1c_), but not pp2a (pp2ac_), increased ps137-pfn1 levels. Pp1c_ binds pfn1 in cultured cells, and this interaction was increased by a phosphomimetic mutation of pfn1 at ser-137 (s137d). Together, these data define pp1 as the principal phosphatase for ser-137 of pfn1

SIGNOR-196816

P12931

Q9NR80

1

phosphorylation

up-regulates

0.312

This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.

SIGNOR-179601

P11021

Q99941

0

transcriptional regulation

up-regulates quantity by expression

0.448

Accordingly, N-terminal fragments of each ATF6 isoform (N-ATF6α and N-ATF6β) were overexpressed in HeLa cells and the effects on GRP78 induction were assessed. When expressed at similar levels, N-ATF6α conferred ∼200-fold greater GRP78 promoter activation than N-ATF6β.

SIGNOR-261566

P11171

Q14980

1

relocalization

up-regulates activity

0.533

These results indicate that 4.1 proteins recruit NuMA and dynein to the anaphase cell cortex through their conserved CTD (Figure 2I).

SIGNOR-266012

Q2M1Z3

P49840

0

phosphorylation

up-regulates activity

0.337

We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.

SIGNOR-262878

Q96B36

P42345

0

phosphorylation

down-regulates activity

0.904

We propose that after mtorc1 kinase activation by upstream regulators, pras40 is phosphorylated directly by mtor, thus contributing to the relief of pras40-mediated substrate competitionwe also find that mutation of ser-221 to ala increases the inhibitory activity of pras40 toward mtorc1.

SIGNOR-178128

P30411

P35626

0

phosphorylation

down-regulates activity

0.2

Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.

SIGNOR-251462

P11166

P04637

0

transcriptional regulation

down-regulates quantity by repression

0.597

P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway.

SIGNOR-267464

O14737

O14829

0

dephosphorylation

down-regulates quantity by destabilization

0.349

Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.

SIGNOR-277008

P53350

P24941

0

phosphorylation

up-regulates activity

0.375

Thus, CycA2-CDK2 can stimulate phosphorylation of PLK1 T210 in vitro and the interactions required for CycA2-mediated PLK1 T210 phosphorylation are detected in the cytoplasm, but not in the nucleus.|We find that Cyclin A2-CDK2 can activate the mitotic kinase PLK1 through phosphorylation of Bora, and that only cytoplasmic Cyclin A2 interacts with Bora and PLK1.

SIGNOR-280212

Q15750

O95147

0

dephosphorylation

down-regulates activity

0.298

DUSP14 directly interacted with TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser (438), leading to TAB1 and TAK1 complex inactivation in T cells.

SIGNOR-277147

Q14940

P68400

0

phosphorylation

down-regulates activity

0.2

CK2 phosphorylation of an acidic Ser/Thr di-isoleucine motif in the Na+/H+ exchanger NHE5 isoform promotes association with beta-arrestin2 and endocytosis

SIGNOR-276250

Q6ZMU5

Q05397

1

ubiquitination

down-regulates quantity by destabilization

0.326

Because RING disrupted MG53 mutants (C14A and DeltaR) did not induce FAK ubiquitination and degradation, the RING domain was determined to be required for MG53 induced FAK ubiquitination.

SIGNOR-278648

P49840

Q07820

1

phosphorylation

down-regulates quantity by destabilization

0.457

MCL-1 was phosphorylated by GSK-3 at a conserved GSK-3 phosphorylation site (S159). Glycogen Synthase Kinase-3 Regulates Mitochondrial Outer Membrane Permeabilization and Apoptosis by Destabilization of MCL-1. threonine 163, which represents the GSK-3 priming phosphorylation in this protein

SIGNOR-251217

Q13164

P51812

1

phosphorylation

up-regulates activity

0.561

This suggested that ERK5 may directly activate RSKs.|In vitro active ERK5 also phosphorylated RSK2 that had been immunoprecipitated from transfected cells using an anti-HA antibody ( Fig. 2 B).|Phosphorylation of RSK2 by ERK5 in vitro increased its activity towards GST-S6 as much as 8-fold (Figs. 2 C and E).

SIGNOR-279216

P63104

P53779

0

phosphorylation

down-regulates

0.2

Jnk phosphorylates 14-3-3zetaat ser-184 and 14-3-3sigmaat ser-190

SIGNOR-124009

P25098

Q14940

1

phosphorylation

down-regulates activity

0.2

Simultaneous mutation of five Ser/Thr residues within 702-714 to Ala ((702)ST/AA(714)) abolished phosphorylation and binding of beta-arrestin2. In transfected cells, the CK2 catalytic alpha subunit formed a complex with NHE5 and decreased wild-type but not (702)ST/AA(714) NHE5 activity, further supporting a regulatory role for this kinase. The rate of internalization of (702)ST/AA(714) was also diminished and relatively insensitive to overexpression of beta-arrestin2.

SIGNOR-275503

P35222

P17612

0

phosphorylation

up-regulates activity

0.478

Although pka did not affect the formation of a complex between glycogen synthase kinase 3beta (gsk-3beta), beta-catenin, and axin, phosphorylation of beta-catenin by pka inhibited ubiquitination of beta-catenin in intact cells and in vitro.

SIGNOR-140902

Q12888

Q9NS91

0

ubiquitination

up-regulates activity

0.611

RAD18 associates with 53BP1 and is recruited to DSB sites in a 53BP1 dependent manner specifically during G1-phase, RAD18 monoubiquitinates KBD domain of 53BP1 at lysine 1268 in vitro.|These results suggest that RAD18 directed modification at Lysine 1268 of 53BP1 promotes the retention of 53BP1 at DSBs.

SIGNOR-278593

Q13131

P08151

1

phosphorylation

down-regulates activity

0.334

AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

SIGNOR-259862

P49715

P06702

1

transcriptional regulation

up-regulates quantity by expression

0.227

Among several known transcription factor binding motifs, nuclear protein(s) of VD3-treated HL-60 cells and THP-1 cells bound to the CCAAT/enhancer binding protein (C/EBP)-binding motif that was located in the upstream region of the MRP14 gene (-81), as evidenced by the competitive gel mobility-shift assay.|Thus, it was concluded that C/EBP alpha and -beta were able to bind to the C/EBP motif, and that C/EBP alpha bound to the motif in THP-1 cells and C/EBP beta bound to that in the VD3-treated HL-60 cells.

SIGNOR-254041

P54725

Q05086

0

polyubiquitination

down-regulates quantity by destabilization

0.486

Here we report the identification of HHR23A, one of the human homologues of the yeast DNA repair protein Rad23, as an E6-independent target of E6AP. E6AP-mediated ubiquitination and degradation of HHR23A and HHR23B.

SIGNOR-272550

P05129

P61764

1

phosphorylation

down-regulates activity

0.386

Munc18a is essential for neurotransmitter release by exocytosis and can be phosphorylated by PKC in vitro on Ser-306 and Ser-313. We demonstrate that it is phosphorylated on Ser-313 in response to phorbol ester treatment in adrenal chromaffin cells. Mutation of both phosphorylation sites to glutamate reduces its affinity for syntaxin and so acts as a phosphomimetic mutation.

SIGNOR-249187

Q9BXH1

Q92570

0

transcriptional regulation

up-regulates quantity by expression

0.2

Over-expression of NR4A3 attenuated proliferation of cancer cells and promoted apoptosis by augmenting the expression of pro-apoptotic genes, PUMA and Bax.

SIGNOR-259396

P23443

P27708

1

phosphorylation

up-regulates activity

0.372

CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.

SIGNOR-267443

Q8N163

P68400

0

phosphorylation

up-regulates activity

0.2

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

SIGNOR-267666

P53350

Q96GD4

0

phosphorylation

up-regulates activity

0.599

Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis.|Thus, we conclude that Aurora B indirectly promotes the phosphorylation of MCAK on Ser715 at the kinetochores through phosphorylation of PLK1 at Thr210 and its ensuing activation.

SIGNOR-279358

Q9UKM9

Q99873

1

post transcriptional regulation

up-regulates quantity

0.247

RALY binds poly-U rich elements within several RNAs and regulates the expression as well as the stability of specific transcripts. Here we show that RALY binds PRMT1 mRNA and regulates its expression.|We demonstrate that RALY down-regulation decreases protein arginine N-methyltransferase 1 levels

SIGNOR-262273

Q06124

Q16620

1

dephosphorylation

down-regulates activity

0.707

Conversely, PTPN11 knockdown lead to increased Y 515 phosphorylation of TrkB compared to the scramble control in the neuronal cells.|This study established that TrkB activation as demonstrated by receptor phosphorylation at Tyr 515 in the SH-SY5Y cells is negatively regulated by PTPN11 actions.

SIGNOR-277123

Q15208

Q13043

0

phosphorylation

up-regulates activity

0.332

Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity.

SIGNOR-279641

A6ND36

P36894

0

phosphorylation

up-regulates activity

0.374

These results indicate that ALK3 phosphorylates PAWS1 predominantly at Ser610 but can also phosphorylate at Ser614 and Ser616 in vitro. |Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway.

SIGNOR-264766

Q13131

Q9Y478

1

phosphorylation

up-regulates

0.925

Mutation of serine 108 to alanine, an autophosphorylation site within the glycogen binding domain of the beta1 subunit, almost completely abolishes activation of ampk by a-769662 in cells and in vitro, while only partially reducing activation by amp

SIGNOR-157553

Q92949

Q5JVL4

1

transcriptional regulation

up-regulates quantity by expression

0.356

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266934

P11413

Q9NXA8

0

catalytic activity

up-regulates activity

0.278

Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.

SIGNOR-261211

P12931

P11511

1

phosphorylation

up-regulates

0.35

Phosphorylation of the 361-tyrosine residue is crucial in the up-regulation of aromatase activity. c-src protein directly phosphorylates aromatase on tyrosine 361.

SIGNOR-186284

P42574

P49810

1

cleavage

up-regulates activity

0.405

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

SIGNOR-261743

P49716

P48436

0

transcriptional regulation

down-regulates quantity by repression

0.272

Sox9 directly binds to the promoter regions of c/ebpbeta and c/ebpdelta to suppress their promoter activity, preventing adipocyte differentiation

SIGNOR-184283

O75496

O14965

0

phosphorylation

up-regulates activity

0.51

Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis.|Thr25 of geminin is phosphorylated by Aurora-A.

SIGNOR-278509

Q9ULU4

P15692

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262041

Q92630

P05412

1

phosphorylation

down-regulates

0.256

Degradation of c-jun/c-myc is a critical process for the g(1)/s transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 ? (gsk3?). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this gsk3? Modification has not been definitively identified. Here, we found that the dual-specificity tyrosine phosphorylation-regulated kinase dyrk2 functions as a priming kinase of c-jun and c-myc.The finding that kinase-active dyrk2 phosphorylated gst_c-jun210_310-wt by detection with an anti_phospho_c-jun(ser243) antibody demonstrated that dyrk2 is a ser243 kinase in vitro

SIGNOR-195771

Q09472

P31751

0

phosphorylation

up-regulates

0.327

We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity

SIGNOR-148987

Q07954

P17612

0

phosphorylation

up-regulates activity

0.324

LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis.

SIGNOR-250000

Q07817

O14920

0

phosphorylation

down-regulates quantity

0.339

We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .

SIGNOR-279529

Q12923

Q15654

1

dephosphorylation

down-regulates activity

0.434

PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.|Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells.

SIGNOR-248713

P24071

P49841

0

phosphorylation

down-regulates activity

0.2

GSK-3 is constitutively active in the absence of cytokine stimulation and can phosphorylate S263, keeping FcalphaRI in the inactive state.

SIGNOR-264857

P27361

P07101

1

phosphorylation

up-regulates

0.482

In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11

SIGNOR-34678

P46531

Q9NWT6

0

hydroxylation

down-regulates

0.55

We show that fih-1 hydroxylates notch icd at two residues (n(1945) and n(2012)) that are critical for the function of notch icd as a transactivator within cells and during neurogenesis and myogenesis in vivo. Fih-1 negatively regulates notch activity and accelerates myogenic differentiation.

SIGNOR-161057

P35968

P23470

0

dephosphorylation

down-regulates activity

0.253

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-254707

P00533

P21860

1

phosphorylation

up-regulates

0.67

The erbb3 protein which possesses little or no intrinsic protein tyrosine kinase activiity is phosphorylated by the activated egf receptor protein tyrosine kinase on tyrosine residues within the yxxm sequence motif. These phosphorylated tyrosine residues interact with the p85 regulatory subunit of pi 3-kinase, which could result in the activation of the p110 catalytic subunit via a conformational mechanism.

SIGNOR-34748

Q01860

Q6U7Q0

0

transcriptional regulation

up-regulates quantity by expression

0.2

Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays revealed that Zfp322a binds to Pou5f1 and Nanog promoters and regulates their transcription.

SIGNOR-264900

Q8IYW5

P16403

1

polyubiquitination

down-regulates

0.2

ITCH biochemically antagonized RNF168 and RNF8 in polyubiquitination of histone H1.2 ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. Both RNF168 and RNF8 elicited higher Ubn levels of K46R-H1.2 compared to WT-H1.2, suggesting that Ubn of H1.2 by both E3 ligases occurs at a site apart from K46.

SIGNOR-272927

O14920

P20749

1

phosphorylation

up-regulates activity

0.365

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277364

Q15046

P27361

0

phosphorylation

up-regulates

0.2

Lysrs serves as a key signaling molecule in the immune response by regulating gene expression. Lysrs was phosphorylated on serine 207 in a mapk-dependent manner, released from the multisynthetase complex, and translocated into the nucleus.

SIGNOR-186125

Q9UM73

P49841

1

phosphorylation

up-regulates activity

0.248

It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells.

SIGNOR-280180

Q96RU2

Q13315

0

phosphorylation

up-regulates activity

0.311

These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.

SIGNOR-279007

Q99638

O14757

0

phosphorylation

up-regulates activity

0.669

Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation.

SIGNOR-279503

P49841

Q16566

0

phosphorylation

down-regulates activity

0.263

CAMK4 phosphorylates GSK3\u03b2 at serine 9, which leads to its inactivation. xref Accordingly, we examined the levels of phosphorylated GSK3\u03b2 at serine 9 (pGSK3\u03b2-ser9) in podocytes exposed to IgG from TG patients and calculated the ratio of pGSK3\u03b2-ser9 to total GSK3\u03b2.

SIGNOR-279142

P35580

Q14814

0

transcriptional regulation

up-regulates quantity by expression

0.322

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

SIGNOR-238766

Q8NC42

P15056

1

polyubiquitination

down-regulates quantity by destabilization

0.337

We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF.

SIGNOR-272043

P19784

Q9NQB0

1

phosphorylation

up-regulates activity

0.378

We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4.

SIGNOR-251044

Q8WWK9

P06493

0

phosphorylation

up-regulates

0.288

Among these, thr-622 was specifically phosphorylated by cdk1-cyclin b1 both in vitro and in vivo. these findings suggest that cdk1-cyclin b1-mediated phosphorylation of tmap is important for and contributes to proper regulation of microtubule dynamics and establishment of functional bipolar spindles during mitosis.

SIGNOR-185317

Q9UKB1

P25963

1

ubiquitination

down-regulates

0.542

We report here the identification of an ikappab-ubiquitin (ub) ligase complex containing the f-box/wd40-repeat protein, beta-trcp, a vertebrate homolog of drosophila slimb. beta-trcp binds to ikappabalpha only when the latter is specifically phosphorylated by an ikappab kinase complex. here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of i kappa b alpha.

SIGNOR-64317

Q13315

Q00987

1

phosphorylation

down-regulates activity

0.756

Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation.

SIGNOR-94268

P19174

Q92830

0

acetylation

down-regulates activity

0.2

The histone acetyltransferase GCN5 (general control non-repressed protein 5) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas sirtuin 1 deacetylates and activates PGC-1alpha.

SIGNOR-275498

P28482

P19438

1

phosphorylation

down-regulates activity

0.5

Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation.|Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a

SIGNOR-249453

Q9UN19

Q06187

0

phosphorylation

up-regulates activity

0.672

We present a number of lines of evidence that in vivo, Src-type tyrosine kinases are responsible for the phosphorylation of tyrosine 139 in DAPP-1. | Although Btk appears to phosphorylate DAPP-1 relatively efficiently both in Sf9 cells and in vitro, we find no evidence that in either B cells or PAE cells Btk family kinases phosphorylate DAPP-1.

SIGNOR-250602

Q9Y6R4

P46734

1

phosphorylation

up-regulates activity

0.639

These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1.

SIGNOR-50891

Q9P289

Q8TDY4

1

phosphorylation

up-regulates activity

0.2

Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.

SIGNOR-272238

P29350

P15498

1

dephosphorylation

down-regulates activity

0.576

SHP-1 dephosphorylates and inactivates the guanine exchange factor Vav1.

SIGNOR-277171

Q13188

P18754

1

phosphorylation

up-regulates

0.2

MST2 Phosphorylates RCC1 In Vitro and In Vivo. Using an antibody generated against phospho-S2/11 in RCC1 [18], we found that these two residues were also efficiently phosphorylated by MST1 and MST2 (Figure 2D), further supporting that S2 and/or S11 are genuine MST2 phosphorylation targets.

SIGNOR-263146

P00734

P08709

1

null

up-regulates activity

0.301

Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind

SIGNOR-263529

P19174

P07948

0

phosphorylation

up-regulates activity

0.656

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249381

P17612

P17655

1

phosphorylation

down-regulates

0.262

Activation of m-calpain (calpain ii) by epidermal growth factor is limited by protein kinase a phosphorylation of m-calpain.These Data point to a novel mechanism of negative control of calpain activation, direct phosphorylation by pka.

SIGNOR-116248

Q9BQA1

P11802

0

phosphorylation

up-regulates activity

0.7

Phosphorylation of MEP50 on Thr 5 by D1T286A and CDK4 is necessary and sufficient to increase the intrinsic methyltransferase activity of PRMT5, resulting in increased H4R3 and H3R8 methylation and repression of the CUL4A/B expression.

SIGNOR-279019

P60953

Q8WZ64

0

gtpase-activating protein

down-regulates activity

0.495

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-260455

O60610

P55283

1

null

up-regulates activity

0.2

Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation.

SIGNOR-253110

Q9C0B5

P21453

1

palmitoylation

up-regulates activity

0.2

We propose that DHHC5-mediated palmitoylation of S1P1R determines Gi coupling and its signalling in a spatio/temporal manner.

SIGNOR-261140

P29474

P41743

0

phosphorylation

down-regulates activity

0.2

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251635

O14867

Q9BYM8

0

ubiquitination

down-regulates quantity by destabilization

0.345

HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.

SIGNOR-236971

Q05655

P07948

0

phosphorylation

down-regulates activity

0.557

Src, Fyn, or Lyn are the essential kinases that tyrosine phosphorylate and inactivate PKC δ. Lyn phosphorylates tyrosine residue 565 in vitro

SIGNOR-251407

Q13224

P05129

0

phosphorylation

up-regulates activity

0.399

These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels.

SIGNOR-249085

P33076

P28482

0

phosphorylation

up-regulates

0.432

We show in this study that the nuclear localized form of ciita is a predominantly phosphorylated form of the protein, whereas cytoplasmic ciita is predominantly unphosphorylated. Novel phosphorylation sites were determined to be located within a region that contains serine residues 286, 288, and 293. Double mutations of these residues increased nuclear ciita, indicating that these sites are not required for nuclear import. Erk1/2-mediated phosphorylation of ciita down-regulates ciita activity by priming it for nuclear export, thus providing a means for cells to tightly regulate the extent of antigen presentation.

SIGNOR-160609

O43150

P62330

1

gtpase-activating protein

up-regulates activity

0.668

Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro.

SIGNOR-269706

P18031

P51692

1

dephosphorylation

down-regulates activity

0.676

A Cytosolic Protein-tyrosine Phosphatase PTP1B Specifically Dephosphorylates and Deactivates Prolactin-activated STAT5a and STAT5b

SIGNOR-248429

P60484

Q05397

1

dephosphorylation

down-regulates activity

0.821

The tumor suppressor PTEN is a phosphatase with sequence homology to tensin. PTEN dephosphorylates phosphatidylinositol 3,4, 5-trisphosphate (PIP3) and focal adhesion kinase (FAK), and it can inhibit cell growth, invasion, migration, and focal adhesions. We investigated molecular interactions of PTEN and FAK in glioblastoma and breast cancer cells lacking PTEN. The PTEN trapping mutant D92A bound wild-type FAK, requiring FAK autophosphorylation site Tyr397

SIGNOR-248547

P14210

Q02447

0

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region.

SIGNOR-251741

P49840

O75444

1

phosphorylation

up-regulates

0.2

We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.

SIGNOR-159358

P11362

Q9P0J1

1

phosphorylation

down-regulates activity

0.292

Here we report that phosphorylation at another tyrosine residue, Tyr-94, inhibits PDP1 by reducing the binding ability of PDP1 to lipoic acid, which is covalently attached to the L2 domain of dihydrolipoyl acetyltransferase (E2) to recruit PDP1 to PDC. We found that multiple oncogenic tyrosine kinases directly phosphorylated PDP1 at Tyr-94, and Tyr-94 phosphorylation of PDP1 was common in diverse human cancer cells and primary leukemia cells from patients.

SIGNOR-276640

P16104

Q9H4B4

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of H2AX at serine 139 was catalyzed by hyperosmotic stress-induced activation of Plk3.|Osmotic stress induced phosphorylation of H2AX by polo like kinase 3 affects cell cycle progression in human corneal epithelial cells.|Our results for the first time reveal that hyperosmotic stress-activated Plk3 elicited \u03b3H2AX.

SIGNOR-280073

P08069

P12004

1

phosphorylation

up-regulates activity

0.2

In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination.

SIGNOR-277252

Q9NXR1

P06493

0

phosphorylation

up-regulates activity

0.654

We found that Nudel and NudE were also phosphorylated in M phase (Fig. (Fig.22 and and3).3). First, Nudel and NudE were specifically phosphorylated in M phase. Moreover, both proteins were phosphorylated by Cdc2 and Erk2 in vitro.Due to conservation of the S/TP motifs, NudE may also be phosphorylated at similar sites by these kinases, though it contains an additional potential Cdk site at S282 (SPNR).

SIGNOR-274077

Q8WV44

Q02156

1

polyubiquitination

down-regulates quantity by destabilization

0.2

RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. The RINCK-mediated ubiquitination is likely to be polyubiquitination, because the ubiquitinated PKCβII was detected as a high molecular weight smear.

SIGNOR-271668

P17676

P17174

1

transcriptional regulation

up-regulates quantity by expression

0.2

In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells. Deletion studies revealed that regions P2 and P4 are critical for promoter activity. In gel retardation experiments, the P4 region bound different C/EBP-related proteins in different tissues

SIGNOR-254051