GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q8WV28	P43405	0	phosphorylation	up-regulates	0.806	The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.	SIGNOR-96044
P12757	Q9HAU4	0	ubiquitination	down-regulates activity	0.738	Tgf-beta also induces the association of smurf2 with the transcriptional co-repressor snon and we show that smad2 can function to mediate this interaction. This allows smurf2 hect domain to target snon for ubiquitin-mediated degradation by the proteasome.	SIGNOR-236090
P29803	Q15119	0	phosphorylation	down-regulates	0.548	Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs.	SIGNOR-143970
Q8N4N8	Q9Y448	0	relocalization	down-regulates activity	0.407	The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.	SIGNOR-252053
Q6PKG0	P31749	0	phosphorylation	down-regulates activity	0.288	LARP1 is a direct substrate of Akt/S6K1 and mTORC1. Akt is a physiologically relevant primary kinase for S770/S979 phosphorylation of LARP1\|Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5’UTRs and relieves its inhibitory activity on RP mRNA translation.	SIGNOR-260992
Q14469	Q8WTT2	1	transcriptional regulation	down-regulates quantity	0.2	The expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes	SIGNOR-253059
P20749	P28482	0	phosphorylation	up-regulates activity	0.474	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-277361
P49674	P15923	1	phosphorylation	up-regulates	0.2	Tcf3 is a substrate for both glycogen synthase kinase (gsk) 3 and casein kinase (ck) 1epsilon, and phosphorylation of tcf3 by ckiepsilon stimulates its binding to beta-catenin, an effect reversed by gsk3.	SIGNOR-110056
P54764	Q14938	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268908
Q96G74	P68400	0	phosphorylation	up-regulates activity	0.2	Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d).	SIGNOR-265872
P21333	Q15418	0	phosphorylation	up-regulates	0.383	We show that the n-terminal kinase domain of rsk phosphorylates flna on ser(2152) in response to mitogens	SIGNOR-123458
P00533	Q14185	1	phosphorylation	up-regulates activity	0.308	Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .\|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.	SIGNOR-279329
O15530	P24723	1	phosphorylation	up-regulates activity	0.316	Protein kinase C(eta) is phosphorylated by PDK1 in vitro, leading to kinase activation as similarly reported for protein kinase C(epsilon) activation by PDK1.	SIGNOR-280062
P46531	Q86Y01	0	ubiquitination	up-regulates activity	0.781	The human Deltex (DTX1) gene encodes a cytoplasmic protein that functions as a positive regulator of the Notch signaling pathway.	SIGNOR-85942
P23759	Q86X55	0	methylation	up-regulates	0.421	Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7	SIGNOR-255898
O15344	Q13153	0	phosphorylation	up-regulates activity	0.2	Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.\|Pak1 promotes Mid1 localization to cortical nodes.	SIGNOR-279307
P27448	P11309	0	phosphorylation	down-regulates	0.418	Here we show that the protein kinase cdc25 c-associated kinase 1 (c-tak1) is a binding partner and a substrate of pim-1.	SIGNOR-128264
O94916	P06493	0	phosphorylation	up-regulates	0.2	High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.	SIGNOR-170882
O43474	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.365	F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression	SIGNOR-273444
Q9NP62	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	We demonstrated that GSK-3beta mediates phosphorylation of GCM1 on Ser322, which is recognized by the F-box protein, FBW2, to promote GCM1 ubiquitination and degradation.	SIGNOR-278940
P13569	P17252	0	phosphorylation	up-regulates activity	0.399	Direct amino acid sequencing and peptide mapping of CF-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by PKA and PKG, and serines 686 and 790 were phosphorylated by PKC.	SIGNOR-248849
O14813	P17612	0	phosphorylation	down-regulates	0.307	Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription.	SIGNOR-186462
Q5JVS0	Q04759	0	phosphorylation	down-regulates activity	0.303	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249256
P16220	P10645	1	transcriptional regulation	up-regulates quantity by expression	0.265	Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.	SIGNOR-254276
P04626	Q12923	0	dephosphorylation	down-regulates activity	0.332	Since a previous report showed PTPN13 may dephosphorylate ErbB2 directly, we also examined levels of phospho-ErbB2 (tyr 1248), and we also observed a small effect in the presence of wild-type PTPN13 (XREF_FIG).\|The fact that both ErbB2 and H-RasV12 were potentiated by PTPN13 loss and PTPN13 inhibited MAP kinase signaling downstream of multiple oncogenes (ErbB2, EGFR, H-RasV12), suggest that the phosphatase target that inhibits MAP kinase signaling may not only be limited to ErbB2 tyrosine 1248.	SIGNOR-277087
Q16566	P46531	1	phosphorylation	up-regulates quantity by stabilization	0.36	In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).	SIGNOR-279596
P15976	P56524	1	relocalization	up-regulates activity	0.584	GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.	SIGNOR-275665
P35222	O96013	0	phosphorylation	up-regulates	0.286	Pak4 interacts with and phosphorylates _-catenin on ser675, which promotes the tcf/lef transcriptional activity and stabilizes _-catenin through inhibition of its degradation.	SIGNOR-191557
P28482	P35568	1	phosphorylation	down-regulates activity	0.68	Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation.	SIGNOR-123173
Q15022	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.362	PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis\|In SUZ12, residues 539, 541 and 546 phosphorylated by Plk1 in vitro	SIGNOR-275555
Q05397	P60484	0	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
Q9UQB8	P54646	0	phosphorylation	down-regulates	0.2	Using this approach for ppp1r12c, baiap2, and cdc27, we found that mutation of a single serine to alanine (s452, s366, and s379 respectively) resulted in almost a complete loss of ampk phosphorylation in these proteins. Termination of irsp53 function is suggested to occur following cdc42 dissociation, kinase phosphorylation of t340 and t360, and subsequent 14-3-3 binding, which competes for sh3 partners, thus allowing filopodial retraction	SIGNOR-195102
P29350	P17252	0	phosphorylation	down-regulates	0.364	Protein kinase calpha therefore critically and negatively regulates shp-1 function, forming part of a mechanism to retain shp-1 in a basal active state through interaction with its sh2 domains, and phosphorylating its c-terminal ser591 upon cellular activation	SIGNOR-126876
Q9ULV4	P68400	0	phosphorylation	up-regulates	0.2	We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain	SIGNOR-196193
P00519	P42224	1	phosphorylation	up-regulates activity	0.343	Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).\|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.	SIGNOR-279491
O15151	P06493	0	phosphorylation	down-regulates	0.407	Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus	SIGNOR-134388
Q12772	P27361	0	phosphorylation	up-regulates	0.392	Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.	SIGNOR-123053
Q9NRA0	P27361	0	phosphorylation	up-regulates	0.521	Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1	SIGNOR-153387
P84022	P67775	0	dephosphorylation	down-regulates	0.2	Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a.	SIGNOR-167480
Q8N122	Q9Y478	0	phosphorylation	down-regulates	0.466	Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.	SIGNOR-173041
P35813	Q9UHD2	1	dephosphorylation	down-regulates activity	0.41	Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-276966
P31749	Q16875	1	phosphorylation	up-regulates	0.427	We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.	SIGNOR-252477
P19784	Q13547	1	phosphorylation	up-regulates activity	0.398	Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.	SIGNOR-250999
P08575	P52333	1	dephosphorylation	down-regulates activity	0.456	CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling	SIGNOR-248359
Q15796	P10398	0	phosphorylation	down-regulates quantity by destabilization	0.37	Araf promotes Smad2 linker phosphorylation through S253.\|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2.	SIGNOR-279391
Q5S007	P35241	1	phosphorylation	up-regulates activity	0.364	LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.	SIGNOR-279203
O75582	Q04206	1	phosphorylation	up-regulates	0.718	Transcriptional activation of the nf-kappab p65 subunit by mitogen- and stress-activated protein kinase-1 (msk1)mutational analysis of p65 revealed ser276 as a target for phosphorylation and transactivation in response to tnf. Moreover, we identified msk1 as a nuclear kinase for p65, since msk1 associates with p65 in a stimulus-dependent way and phosphorylates p65 at ser276.	SIGNOR-99210
P12694	O14874	0	phosphorylation	down-regulates	0.609	Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.	SIGNOR-25084
Q7Z5J4	O15516	1	transcriptional regulation	up-regulates quantity by expression	0.479	RAI1 Transcriptionally Activates CLOCK via an Intron 1 Enhancer Element. data suggest that RAI1 binds, directly or in a complex, to the first intron of CLOCK and enhances its transcriptional activity in vitro, supporting RAI1 as a positive regulator of CLOCK and an important part of the circadian loop of transcription. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others.	SIGNOR-266839
Q96PH1	Q9UQM7	0	phosphorylation	up-regulates activity	0.2	In vitro phosphorylation assays revealed that CAMKII can directly phosphorylate Nox5 on Thr494 and Ser498 as detected by phosphorylation state-specific antibodies. Mass spectrometry (MS) analysis revealed the phosphorylation of additional, novel sites at Ser475, Ser502, and Ser675. Of these phosphorylation sites, mutation of only Ser475 to alanine prevented CAMKII-induced increases in Nox5 activity. Together, these results suggest that CAMKII can positively regulate Nox5 activity via the phosphorylation of Ser475.	SIGNOR-276329
P12931	P48048	1	phosphorylation	down-regulates	0.312	Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1	SIGNOR-97803
Q9NTX7	Q9H2G9	1	ubiquitination	down-regulates quantity by destabilization	0.409	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263340
Q9H6Z4	P84022	1	relocalization	down-regulates	0.389	Ranbp3 directly recognizes dephosphorylated smad2/3, which results from the activity of nuclear smad phosphatases, and mediates nuclear export of smad2/3 in a ran-dependent manner	SIGNOR-184608
A6NFN3	O00712	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268912
Q9NRR5	Q13315	0	phosphorylation	up-regulates activity	0.2	These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease	SIGNOR-265076
P20941	P25098	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability\|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).	SIGNOR-279411
P53041	P04150	1	dephosphorylation	down-regulates activity	0.541	Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation.\|Inhibition of GR phosphorylation at Ser-211 is associated with decreased nuclear retention of GR and decreased gene transcription.	SIGNOR-248538
P11362	P56945	1	phosphorylation	up-regulates	0.256	Five tyrosine phosphorylation sites were identified in p130cas on tyr-128, tyr-249, tyr-306, tyr-327, and tyr-410. These tyrosine residues are all located in the substrate domain of p130cas that mediates binding to the sh2 domain of the adaptor molecule crk. Fgf-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125fak and p130cas.	SIGNOR-82760
Q9UNE7	Q13950	1	ubiquitination	down-regulates quantity by destabilization	0.407	Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation.	SIGNOR-278600
Q49MG5	P53350	0	phosphorylation	up-regulates	0.275	We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner	SIGNOR-166564
P31751	P49841	1	phosphorylation	down-regulates activity	0.623	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1	SIGNOR-245420
P08047	P08581	1	transcriptional regulation	up-regulates quantity by expression	0.319	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-241490
P35398	Q99743	1	transcriptional regulation	up-regulates quantity by expression	0.665	Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267980
Q13233	P52564	1	phosphorylation	up-regulates	0.454	Both wild type and kinase-inactive mutant rip immunoprecipitates can active mkk6 in vitrohe sapks are activated by at least two meks, sapk/erk kinase-1 (sek1, also called mapk-kinase (mkk)) and mkk7	SIGNOR-59679
O00562	P28482	0	phosphorylation	up-regulates	0.2	Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis.	SIGNOR-124646
Q5VWQ8	P01111	1	gtpase-activating protein	down-regulates activity	0.494	The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.	SIGNOR-254747
P10589	P22888	1	transcriptional regulation	down-regulates quantity by repression	0.275	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266218
Q13043	Q6ZVD8	0	dephosphorylation	up-regulates activity	0.2	PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis.	SIGNOR-248730
Q96J92	P12931	0	phosphorylation	down-regulates activity	0.2	Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.	SIGNOR-276897
O14744	Q15831	0	phosphorylation	up-regulates activity	0.2	We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.	SIGNOR-277412
O76039	P49418	1	phosphorylation	down-regulates activity	0.36	This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.\| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis	SIGNOR-245881
P11308	O15550	0	transcriptional regulation	down-regulates quantity by repression	0.2	Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase	SIGNOR-260033
O14939	P52333	0	phosphorylation	up-regulates	0.407	We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.	SIGNOR-163858
P17612	P18846	1	phosphorylation	up-regulates activity	0.451	PKA catalytic subunit phosphorylates ATF-1 at Ser63 and that phosphorylation is essential for efficient DNA binding by ATF-1.	SIGNOR-250336
P31749	Q96BF3	1	phosphorylation	up-regulates activity	0.2	We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220.	SIGNOR-273481
O00418	Q96QT4	0	phosphorylation	up-regulates activity	0.314	TRPM7 interacts with, and phosphorylates mouse eEF2-k at serine site 77	SIGNOR-277923
P15408	P15407	1	transcriptional regulation	up-regulates quantity by expression	0.403	Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.	SIGNOR-261602
Q13501	Q9BY78	0	ubiquitination	up-regulates activity	0.358	SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors.	SIGNOR-269830
P12830	P40424	0	transcriptional regulation	up-regulates quantity by expression	0.267	We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4.	SIGNOR-267241
Q969H0	Q9UBK2	1	ubiquitination	down-regulates quantity by destabilization	0.398	We then examined the effect of necdin on ubiquitin-dependent degradation of PGC-1α using Rnf34, a PGC-1α E3 ubiquitin ligase22. Rnf34 reduced the PGC-1α level, and necdin completely inhibited the reduction (Fig. 4i). In addition, necdin strongly suppressed Rnf34-mediated ubiquitination of PGC-1α (Fig. 4j). Necdin also protected PGC-1α against ubiquitination mediated by Fbxw7, another PGC-1α E3 ubiquitin ligase23 (Fig. 4k). These data indicate that necdin stabilizes PGC-1α by inhibiting its degradation in the ubiquitin-proteasomal system.	SIGNOR-253394
O43567	O95295	1	polyubiquitination	up-regulates activity	0.521	RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.	SIGNOR-272044
P17706	P42226	1	dephosphorylation	down-regulates activity	0.679	These results identify TCPTP as a physiological regulator of STAT6 phosphorylation and suggest that specific increases in TCPTP expression in ABC-like DLBCLs may contribute to the different biological characteristics of these tumors	SIGNOR-235192
Q15831	P06241	0	phosphorylation	down-regulates activity	0.327	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.	SIGNOR-278477
Q13950	P31749	0	phosphorylation	down-regulates activity	0.446	Here we show that Akt kinase directly phosphorylates Runx2 to regulate invasive properties of breast cancer cells.	SIGNOR-280176
Q15797	Q9GZU7	0	dephosphorylation	down-regulates	0.498	In human cells, rnai-mediated depletion of scp1 and scp2 increases the extent and duration of smad1 phosphorylation in response to bmp, the transcriptional action of smad1, and the strength of endogenous bmp gene responses. The present identification of the scp family as smad c-terminal phosphatases sheds light on the events that attenuate smad signaling and reveals unexpected links to the essential phosphatases that control rna polymerase ii in eukaryotes.	SIGNOR-148396
O00505	P46531	1	relocalization	up-regulates	0.324	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.	SIGNOR-165280
Q9UHC7	P04637	1	polyubiquitination	down-regulates quantity by destabilization	0.431	Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. K291 and K292 of p53 are required for MKRN1-mediated degradation and ubiquitination of p53	SIGNOR-271846
Q9UQM7	O00631	1	phosphorylation	down-regulates activity	0.241	SLN is also phosphorylated by CaMKII at Thr 5, and a phosphorylation mimic (Thr5Glu mutation) abolishes the inhibitory function of ectopically expressed SLN in adult rat ventricular myocytes\| Thr 5 interacts with SERCA Trp 932, and phosphorylation at this site would cause a steric clash that destabilizes binding	SIGNOR-264778
Q00987	Q92993	1	polyubiquitination	down-regulates quantity by destabilization	0.654	Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.	SIGNOR-272613
P00533	Q13501	1	phosphorylation	down-regulates activity	0.33	Here we found that EGFR-stimulated phosphorylation of SQSTM1 at tyrosine 433 induces dimerization of its UBA domain, which disturbs the sequestration function of SQSTM1 and causes autophagic flux blocking.	SIGNOR-277500
Q8TEK3	Q9Y4D8	1	transcriptional regulation	down-regulates quantity by repression	0.2	Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.	SIGNOR-267150
P42858	P17612	0	phosphorylation	down-regulates quantity by destabilization	0.2	Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels.	SIGNOR-277625
O14672	P01133	1	cleavage	up-regulates activity	0.566	Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin	SIGNOR-259840
O00712	A6NFN3	1	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268912
O96017	P06400	1	phosphorylation	up-regulates activity	0.423	Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1	SIGNOR-153908
Q13315	Q15831	1	phosphorylation	up-regulates	0.571	We demonstrate that both dna-pk and atm efficiently phosphorylate lkb1 at thr-366 in vitro and provide evidence that atm mediates this phosphorylation in vivo.	SIGNOR-92873
Q9NPD5	P53567	0	transcriptional regulation	up-regulates quantity by expression	0.2	Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.	SIGNOR-268986
P24666	Q9Y243	1	dephosphorylation	down-regulates activity	0.2	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248457
P42224	O14543	1	transcriptional regulation	up-regulates quantity by expression	0.677	Expression of SOCS1 and SOCS3 is regulated primarily by activation of STAT1 and STAT3, respectively, although their expression can be mediated through other signaling cascades, including the mitogen activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways.	SIGNOR-249565
Q9P2P6	P53350	0	phosphorylation	down-regulates quantity by destabilization	0.309	NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.	SIGNOR-279806

Q8WV28

P43405

0

phosphorylation

up-regulates

0.806

The phosphorylation of multiple tyrosine residues not only amplifies plcgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex.

SIGNOR-96044

P12757

Q9HAU4

0

ubiquitination

down-regulates activity

0.738

Tgf-beta also induces the association of smurf2 with the transcriptional co-repressor snon and we show that smad2 can function to mediate this interaction. This allows smurf2 hect domain to target snon for ubiquitin-mediated degradation by the proteasome.

SIGNOR-236090

P29803

Q15119

0

phosphorylation

down-regulates

0.548

Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs.

SIGNOR-143970

Q8N4N8

Q9Y448

0

relocalization

down-regulates activity

0.407

The protein astrin has been shown to remove Kif2b from kinetochores in metaphase through competitive binding of CLASP1 (Manning et al., 2010 blue right-pointing triangle). During prometaphase, Aurora B kinase activity prevents astrin from localizing to kinetochores (Manning et al., 2010 blue right-pointing triangle; Schmidt et al., 2010 blue right-pointing triangle). This permits Kif2b to localize to kinetochores to destabilize k-MT attachments to execute error correction through Plk1-dependent recruitment and activation.

SIGNOR-252053

Q6PKG0

P31749

0

phosphorylation

down-regulates activity

0.288

LARP1 is a direct substrate of Akt/S6K1 and mTORC1. Akt is a physiologically relevant primary kinase for S770/S979 phosphorylation of LARP1|Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5’UTRs and relieves its inhibitory activity on RP mRNA translation.

SIGNOR-260992

Q14469

Q8WTT2

1

transcriptional regulation

down-regulates quantity

0.2

The expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes

SIGNOR-253059

P20749

P28482

0

phosphorylation

up-regulates activity

0.474

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-277361

P49674

P15923

1

phosphorylation

up-regulates

0.2

Tcf3 is a substrate for both glycogen synthase kinase (gsk) 3 and casein kinase (ck) 1epsilon, and phosphorylation of tcf3 by ckiepsilon stimulates its binding to beta-catenin, an effect reversed by gsk3.

SIGNOR-110056

P54764

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268908

Q96G74

P68400

0

phosphorylation

up-regulates activity

0.2

Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d).

SIGNOR-265872

P21333

Q15418

0

phosphorylation

up-regulates

0.383

We show that the n-terminal kinase domain of rsk phosphorylates flna on ser(2152) in response to mitogens

SIGNOR-123458

P00533

Q14185

1

phosphorylation

up-regulates activity

0.308

Here we report that EGFRvIII induces serine phosphorylation at serine residue 1250 (S1250) of Dock180 (p-Dock180 S1250 ) and that p-Dock180 S1250 is required for EGFRvIII-promoted Rac1 activation, glioblastoma cell growth, survival and invasion in vitro and in vivo .|We demonstrate that EGFRvIII induces serine phosphorylation of Dock180, stimulates Rac1 activation and glioma cell migration.

SIGNOR-279329

O15530

P24723

1

phosphorylation

up-regulates activity

0.316

Protein kinase C(eta) is phosphorylated by PDK1 in vitro, leading to kinase activation as similarly reported for protein kinase C(epsilon) activation by PDK1.

SIGNOR-280062

P46531

Q86Y01

0

ubiquitination

up-regulates activity

0.781

The human Deltex (DTX1) gene encodes a cytoplasmic protein that functions as a positive regulator of the Notch signaling pathway.

SIGNOR-85942

P23759

Q86X55

0

methylation

up-regulates

0.421

Carm1 specifically methylates Pax7 at multiple arginine residues in the N terminus of Pax7

SIGNOR-255898

O15344

Q13153

0

phosphorylation

up-regulates activity

0.2

Pak1 phosphorylates the N-terminus of Mid1 to promote its association with cortical nodes.|Pak1 promotes Mid1 localization to cortical nodes.

SIGNOR-279307

P27448

P11309

0

phosphorylation

down-regulates

0.418

Here we show that the protein kinase cdc25 c-associated kinase 1 (c-tak1) is a binding partner and a substrate of pim-1.

SIGNOR-128264

O94916

P06493

0

phosphorylation

up-regulates

0.2

High nacl-induced activation of cdk5 increases phosphorylation of the osmoprotective transcription factor tonebp/orebp at threonine 135, which contributes to its rapid nuclear localization. we performed in vitro kinase assays using the tonebp/orebp peptide containing t135 as substrate (figure 3b, right panel) and various recombinant kinases. The peptide is strongly phosphorylated by cdk5, less by cdk1.

SIGNOR-170882

O43474

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.365

F-box protein FBXO22 mediates polyubiquitination and degradation of KLF4 to promote hepatocellular carcinoma progression

SIGNOR-273444

Q9NP62

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

We demonstrated that GSK-3beta mediates phosphorylation of GCM1 on Ser322, which is recognized by the F-box protein, FBW2, to promote GCM1 ubiquitination and degradation.

SIGNOR-278940

P13569

P17252

0

phosphorylation

up-regulates activity

0.399

Direct amino acid sequencing and peptide mapping of CF-2 revealed that serines 660, 700, 737, and 813 as well as serine 768, serine 795, or both were phosphorylated by PKA and PKG, and serines 686 and 790 were phosphorylated by PKC.

SIGNOR-248849

O14813

P17612

0

phosphorylation

down-regulates

0.307

Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription.

SIGNOR-186462

Q5JVS0

Q04759

0

phosphorylation

down-regulates activity

0.303

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249256

P16220

P10645

1

transcriptional regulation

up-regulates quantity by expression

0.265

Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.

SIGNOR-254276

P04626

Q12923

0

dephosphorylation

down-regulates activity

0.332

Since a previous report showed PTPN13 may dephosphorylate ErbB2 directly, we also examined levels of phospho-ErbB2 (tyr 1248), and we also observed a small effect in the presence of wild-type PTPN13 (XREF_FIG).|The fact that both ErbB2 and H-RasV12 were potentiated by PTPN13 loss and PTPN13 inhibited MAP kinase signaling downstream of multiple oncogenes (ErbB2, EGFR, H-RasV12), suggest that the phosphatase target that inhibits MAP kinase signaling may not only be limited to ErbB2 tyrosine 1248.

SIGNOR-277087

Q16566

P46531

1

phosphorylation

up-regulates quantity by stabilization

0.36

In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ).

SIGNOR-279596

P15976

P56524

1

relocalization

up-regulates activity

0.584

GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells.

SIGNOR-275665

P35222

O96013

0

phosphorylation

up-regulates

0.286

Pak4 interacts with and phosphorylates _-catenin on ser675, which promotes the tcf/lef transcriptional activity and stabilizes _-catenin through inhibition of its degradation.

SIGNOR-191557

P28482

P35568

1

phosphorylation

down-regulates activity

0.68

Rin beta-cells exposed to high glucose exhibited increased c-jun n-terminal kinase (jnk) and erk1/2 activity, which was associated with increased irs-1 phosphorylation at serine (ser)(307) and ser(612), respectively, that inhibits coupling of irs-1 to the insulin receptor and is upstream of the inhibition of irs-1 tyrosine phosphorylation.

SIGNOR-123173

Q15022

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.362

PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis|In SUZ12, residues 539, 541 and 546 phosphorylated by Plk1 in vitro

SIGNOR-275555

Q05397

P60484

0

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

Q9UQB8

P54646

0

phosphorylation

down-regulates

0.2

Using this approach for ppp1r12c, baiap2, and cdc27, we found that mutation of a single serine to alanine (s452, s366, and s379 respectively) resulted in almost a complete loss of ampk phosphorylation in these proteins. Termination of irsp53 function is suggested to occur following cdc42 dissociation, kinase phosphorylation of t340 and t360, and subsequent 14-3-3 binding, which competes for sh3 partners, thus allowing filopodial retraction

SIGNOR-195102

P29350

P17252

0

phosphorylation

down-regulates

0.364

Protein kinase calpha therefore critically and negatively regulates shp-1 function, forming part of a mechanism to retain shp-1 in a basal active state through interaction with its sh2 domains, and phosphorylating its c-terminal ser591 upon cellular activation

SIGNOR-126876

Q9ULV4

P68400

0

phosphorylation

up-regulates

0.2

We demonstrate that crn2 is a binding partner and substrate of protein kinase ck2, which phosphorylates crn2 at s463 in its c-terminal coiled coil domain

SIGNOR-196193

P00519

P42224

1

phosphorylation

up-regulates activity

0.343

Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.

SIGNOR-279491

O15151

P06493

0

phosphorylation

down-regulates

0.407

Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus

SIGNOR-134388

Q12772

P27361

0

phosphorylation

up-regulates

0.392

Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.

SIGNOR-123053

Q9NRA0

P27361

0

phosphorylation

up-regulates

0.521

Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1

SIGNOR-153387

P84022

P67775

0

dephosphorylation

down-regulates

0.2

Accordingly, smad3-associated pp2a activity was found under hypoxic conditions. Hypoxia attenuated the nuclear accumulation of tgf-beta-induced smad3 but did not affect smad2. Moreover, the influence of tgf-beta on a set of smad3-activated genes was attenuated by hypoxia, and this was reversed by chemical pp2a inhibition. Our data demonstrate the existence of a smad3-specific phosphatase and identify a novel role for pp2a.

SIGNOR-167480

Q8N122

Q9Y478

0

phosphorylation

down-regulates

0.466

Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2.

SIGNOR-173041

P35813

Q9UHD2

1

dephosphorylation

down-regulates activity

0.41

Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-276966

P31749

Q16875

1

phosphorylation

up-regulates

0.427

We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.

SIGNOR-252477

P19784

Q13547

1

phosphorylation

up-regulates activity

0.398

Human HDAC1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, Ser(421) and Ser(423), were unambiguously identified. Loss of phosphorylation at Ser(421) and Ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of HDAC1.

SIGNOR-250999

P08575

P52333

1

dephosphorylation

down-regulates activity

0.456

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling

SIGNOR-248359

Q15796

P10398

0

phosphorylation

down-regulates quantity by destabilization

0.37

Araf promotes Smad2 linker phosphorylation through S253.|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2.

SIGNOR-279391

Q5S007

P35241

1

phosphorylation

up-regulates activity

0.364

LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.

SIGNOR-279203

O75582

Q04206

1

phosphorylation

up-regulates

0.718

Transcriptional activation of the nf-kappab p65 subunit by mitogen- and stress-activated protein kinase-1 (msk1)mutational analysis of p65 revealed ser276 as a target for phosphorylation and transactivation in response to tnf. Moreover, we identified msk1 as a nuclear kinase for p65, since msk1 associates with p65 in a stimulus-dependent way and phosphorylates p65 at ser276.

SIGNOR-99210

P12694

O14874

0

phosphorylation

down-regulates

0.609

Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.

SIGNOR-25084

Q7Z5J4

O15516

1

transcriptional regulation

up-regulates quantity by expression

0.479

RAI1 Transcriptionally Activates CLOCK via an Intron 1 Enhancer Element. data suggest that RAI1 binds, directly or in a complex, to the first intron of CLOCK and enhances its transcriptional activity in vitro, supporting RAI1 as a positive regulator of CLOCK and an important part of the circadian loop of transcription. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others.

SIGNOR-266839

Q96PH1

Q9UQM7

0

phosphorylation

up-regulates activity

0.2

In vitro phosphorylation assays revealed that CAMKII can directly phosphorylate Nox5 on Thr494 and Ser498 as detected by phosphorylation state-specific antibodies. Mass spectrometry (MS) analysis revealed the phosphorylation of additional, novel sites at Ser475, Ser502, and Ser675. Of these phosphorylation sites, mutation of only Ser475 to alanine prevented CAMKII-induced increases in Nox5 activity. Together, these results suggest that CAMKII can positively regulate Nox5 activity via the phosphorylation of Ser475.

SIGNOR-276329

P12931

P48048

1

phosphorylation

down-regulates

0.312

Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1

SIGNOR-97803

Q9NTX7

Q9H2G9

1

ubiquitination

down-regulates quantity by destabilization

0.409

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263340

Q9H6Z4

P84022

1

relocalization

down-regulates

0.389

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

SIGNOR-184608

A6NFN3

O00712

0

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268912

Q9NRR5

Q13315

0

phosphorylation

up-regulates activity

0.2

These results suggest that UBQLN4 phosphorylation on S318 is functionally important for its role in the DSB response.>Particularly HRR is dependent on ATM activity (Dietlein et al., 2014). Here, we showed that UBQLN4 is an ATM substrate and that DSB sealing is markedly impaired in UBQLN4-depleted cells. HRR depends on a 5′-3′ DSB end resection, which is initiated by the MRE11 nuclease

SIGNOR-265076

P20941

P25098

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).

SIGNOR-279411

P53041

P04150

1

dephosphorylation

down-regulates activity

0.541

Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation.|Inhibition of GR phosphorylation at Ser-211 is associated with decreased nuclear retention of GR and decreased gene transcription.

SIGNOR-248538

P11362

P56945

1

phosphorylation

up-regulates

0.256

Five tyrosine phosphorylation sites were identified in p130cas on tyr-128, tyr-249, tyr-306, tyr-327, and tyr-410. These tyrosine residues are all located in the substrate domain of p130cas that mediates binding to the sh2 domain of the adaptor molecule crk. Fgf-1-transduced fibroblasts demonstrated a > 10-fold increase in migration, an observation correlated with increased tyrosine phosphorylation of p125fak and p130cas.

SIGNOR-82760

Q9UNE7

Q13950

1

ubiquitination

down-regulates quantity by destabilization

0.407

Here, we show that CHIP promotes Runx2 ubiquitination and degradation and thereby negatively regulates osteoblast differentiation.

SIGNOR-278600

Q49MG5

P53350

0

phosphorylation

up-regulates

0.275

We also demonstrate that asap is a novel substrate of plk1 phosphorylation and have identified serine 289 as the major phosphorylation site by plk1 in vivo. Asap phosphorylated on serine 289 is localized to centrosomes during mitosis, but this phosphorylation is not required for its plk1-dependent localization at the spindle poles. We show that phosphorylated asap on serine 289 contributes to spindle pole stability in a microtubule-dependent manner

SIGNOR-166564

P31751

P49841

1

phosphorylation

down-regulates activity

0.623

Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

SIGNOR-245420

P08047

P08581

1

transcriptional regulation

up-regulates quantity by expression

0.319

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-241490

P35398

Q99743

1

transcriptional regulation

up-regulates quantity by expression

0.665

Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267980

Q13233

P52564

1

phosphorylation

up-regulates

0.454

Both wild type and kinase-inactive mutant rip immunoprecipitates can active mkk6 in vitrohe sapks are activated by at least two meks, sapk/erk kinase-1 (sek1, also called mapk-kinase (mkk)) and mkk7

SIGNOR-59679

O00562

P28482

0

phosphorylation

up-regulates

0.2

Both cdk1 and erk2 induced phosphorylation of the wild-type nir2. Substitution of t794 by alanine reduced the phosphorylation by erk2, whereas the double mutations t794/1223a completely abolished it. The requirement of multiple nir2 phosphorylation sites for plk1 binding may provide a mechanism that sets a threshold for the nir2-plk1 interaction during mitosis.

SIGNOR-124646

Q5VWQ8

P01111

1

gtpase-activating protein

down-regulates activity

0.494

The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.

SIGNOR-254747

P10589

P22888

1

transcriptional regulation

down-regulates quantity by repression

0.275

Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.

SIGNOR-266218

Q13043

Q6ZVD8

0

dephosphorylation

up-regulates activity

0.2

PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis.

SIGNOR-248730

Q96J92

P12931

0

phosphorylation

down-regulates activity

0.2

Using Western blot and mass spectrometry, we now identify three sites in WNK4 that are phosphorylated by c-Src: Tyr(1092), Tyr(1094), and Tyr(1143), and show that both c-Src and protein tyrosine phosphatase type 1D (PTP-1D) coimmunoprecipitate with WNK4.

SIGNOR-276897

O14744

Q15831

0

phosphorylation

up-regulates activity

0.2

We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.

SIGNOR-277412

O76039

P49418

1

phosphorylation

down-regulates activity

0.36

This 120-kDa protein was identified as amphiphysin 1 (Amph1) by LC-MS/MS analysis, and the site of phosphorylation by CDKL5 was determined to be Ser-293.| The phosphorylation mimic mutants, Amph1(S293E) and Amph1(S293D), showed significantly reduced affinity for endophilin, a protein involved in synaptic vesicle endocytosis

SIGNOR-245881

P11308

O15550

0

transcriptional regulation

down-regulates quantity by repression

0.2

Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase

SIGNOR-260033

O14939

P52333

0

phosphorylation

up-regulates

0.407

We identified three kinases capable of phosphorylating pld2 in vitro-epidermal growth factor receptor (egfr), jak3, and src (with jak3 reported for the first time in this study)-that phosphorylate an inhibitory, an activator, and an ambivalent (one that can yield either effect) site, respectively. Mass spectrometry analyses indicated the target of each of these kinases as y(296) for egfr, y(415) for jak3, and y(511) for src.

SIGNOR-163858

P17612

P18846

1

phosphorylation

up-regulates activity

0.451

PKA catalytic subunit phosphorylates ATF-1 at Ser63 and that phosphorylation is essential for efficient DNA binding by ATF-1.

SIGNOR-250336

P31749

Q96BF3

1

phosphorylation

up-regulates activity

0.2

We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220.

SIGNOR-273481

O00418

Q96QT4

0

phosphorylation

up-regulates activity

0.314

TRPM7 interacts with, and phosphorylates mouse eEF2-k at serine site 77

SIGNOR-277923

P15408

P15407

1

transcriptional regulation

up-regulates quantity by expression

0.403

Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.

SIGNOR-261602

Q13501

Q9BY78

0

ubiquitination

up-regulates activity

0.358

SQSTM1 Is a Substrate for RNF26 and the DUB USP15. Catalytically competent RNF26 (light red) recruits SQSTM1 (blue) and mediates ubiquitin ligation (red), which serves to attract UBDs of specific vesicle-associated adaptors.

SIGNOR-269830

P12830

P40424

0

transcriptional regulation

up-regulates quantity by expression

0.267

We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4.

SIGNOR-267241

Q969H0

Q9UBK2

1

ubiquitination

down-regulates quantity by destabilization

0.398

We then examined the effect of necdin on ubiquitin-dependent degradation of PGC-1α using Rnf34, a PGC-1α E3 ubiquitin ligase22. Rnf34 reduced the PGC-1α level, and necdin completely inhibited the reduction (Fig. 4i). In addition, necdin strongly suppressed Rnf34-mediated ubiquitination of PGC-1α (Fig. 4j). Necdin also protected PGC-1α against ubiquitination mediated by Fbxw7, another PGC-1α E3 ubiquitin ligase23 (Fig. 4k). These data indicate that necdin stabilizes PGC-1α by inhibiting its degradation in the ubiquitin-proteasomal system.

SIGNOR-253394

O43567

O95295

1

polyubiquitination

up-regulates activity

0.521

RNF13 directly interacted with snapin, a SNAP-25-interacting protein. Interestingly, snapin was ubiquitinated by RNF13 via the lysine-29 conjugated polyubiquitin chain, which in turn promoted the association of snapin with SNAP-25. Consistently, we found an attenuated interaction between snapin and SNAP-25 in the RNF13-null mice. Therefore, these results suggest that RNF13 is involved in the regulation of the SNARE complex, which thereby controls synaptic function.

SIGNOR-272044

P17706

P42226

1

dephosphorylation

down-regulates activity

0.679

These results identify TCPTP as a physiological regulator of STAT6 phosphorylation and suggest that specific increases in TCPTP expression in ABC-like DLBCLs may contribute to the different biological characteristics of these tumors

SIGNOR-235192

Q15831

P06241

0

phosphorylation

down-regulates activity

0.327

Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.

SIGNOR-278477

Q13950

P31749

0

phosphorylation

down-regulates activity

0.446

Here we show that Akt kinase directly phosphorylates Runx2 to regulate invasive properties of breast cancer cells.

SIGNOR-280176

Q15797

Q9GZU7

0

dephosphorylation

down-regulates

0.498

In human cells, rnai-mediated depletion of scp1 and scp2 increases the extent and duration of smad1 phosphorylation in response to bmp, the transcriptional action of smad1, and the strength of endogenous bmp gene responses. The present identification of the scp family as smad c-terminal phosphatases sheds light on the events that attenuate smad signaling and reveals unexpected links to the essential phosphatases that control rna polymerase ii in eukaryotes.

SIGNOR-148396

O00505

P46531

1

relocalization

up-regulates

0.324

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.

SIGNOR-165280

Q9UHC7

P04637

1

polyubiquitination

down-regulates quantity by destabilization

0.431

Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. K291 and K292 of p53 are required for MKRN1-mediated degradation and ubiquitination of p53

SIGNOR-271846

Q9UQM7

O00631

1

phosphorylation

down-regulates activity

0.241

SLN is also phosphorylated by CaMKII at Thr 5, and a phosphorylation mimic (Thr5Glu mutation) abolishes the inhibitory function of ectopically expressed SLN in adult rat ventricular myocytes| Thr 5 interacts with SERCA Trp 932, and phosphorylation at this site would cause a steric clash that destabilizes binding

SIGNOR-264778

Q00987

Q92993

1

polyubiquitination

down-regulates quantity by destabilization

0.654

Furthermore, we provide evidence that Mdm2, the ubiquitin ligase of the p53 tumour suppressor, interacts physically with Tip60 and induces its ubiquitylation and proteasome-dependent degradation.

SIGNOR-272613

P00533

Q13501

1

phosphorylation

down-regulates activity

0.33

Here we found that EGFR-stimulated phosphorylation of SQSTM1 at tyrosine 433 induces dimerization of its UBA domain, which disturbs the sequestration function of SQSTM1 and causes autophagic flux blocking.

SIGNOR-277500

Q8TEK3

Q9Y4D8

1

transcriptional regulation

down-regulates quantity by repression

0.2

Overexpression of DOT1L decreased the expression of HECTD4 and MYCBP2 in LNCaP, C42B, and 22rv1 cells (Supplementary Fig. 5c), suggesting that DOT1L plays a role in repressing these targets either directly or indirectly.

SIGNOR-267150

P42858

P17612

0

phosphorylation

down-regulates quantity by destabilization

0.2

Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels.

SIGNOR-277625

O14672

P01133

1

cleavage

up-regulates activity

0.566

Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin

SIGNOR-259840

O00712

A6NFN3

1

transcriptional regulation

up-regulates quantity

0.2

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268912

O96017

P06400

1

phosphorylation

up-regulates activity

0.423

Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1

SIGNOR-153908

Q13315

Q15831

1

phosphorylation

up-regulates

0.571

We demonstrate that both dna-pk and atm efficiently phosphorylate lkb1 at thr-366 in vitro and provide evidence that atm mediates this phosphorylation in vivo.

SIGNOR-92873

Q9NPD5

P53567

0

transcriptional regulation

up-regulates quantity by expression

0.2

Taken together, these findings suggest that the LPS-induced down-regulation of Oatp4 is likely due to reduction in the binding of HNF1alpha, C/EBP, HNF3, and RXR:RAR to the Oatp4 promoter.

SIGNOR-268986

P24666

Q9Y243

1

dephosphorylation

down-regulates activity

0.2

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248457

P42224

O14543

1

transcriptional regulation

up-regulates quantity by expression

0.677

Expression of SOCS1 and SOCS3 is regulated primarily by activation of STAT1 and STAT3, respectively, although their expression can be mediated through other signaling cascades, including the mitogen activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways.

SIGNOR-249565

Q9P2P6

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.309

NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.

SIGNOR-279806