GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P46937	O00506	0	phosphorylation	up-regulates activity	0.265	Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.\|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.	SIGNOR-278993
Q2NKX8	P53350	0	relocalization	up-regulates	0.88	Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region	SIGNOR-152136
Q9H3D4	Q6ZMZ3	1	transcriptional regulation	up-regulates quantity by expression	0.2	Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.	SIGNOR-263280
O43524	O15111	0	phosphorylation	down-regulates	0.572	Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation.	SIGNOR-124203
Q93079	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265391
P27361	Q9H9S0	1	phosphorylation	down-regulates	0.492	We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.\|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.	SIGNOR-278487
P04629	P06241	0	phosphorylation	up-regulates activity	0.254	Here, we demonstrate that Fyn can directly phosphorylate the intracellular domain of TrkA and that its kinase activity towards Trk is increased by GPCR stimulation ( Fig. 4 ).	SIGNOR-279410
P51812	Q9H6Z4	1	phosphorylation	up-regulates quantity	0.328	RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran	SIGNOR-276148
P24941	Q14106	1	phosphorylation	up-regulates activity	0.246	Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.	SIGNOR-273601
P68400	P52907	1	phosphorylation	up-regulates	0.2	We demonstrate that ser9 of cpalpha is phosphorylated by protein kinase ck2 in vitro, that cpalpha is phosphorylated in vivo. Finally, we demonstrate that ckip-1 and ck2 inhibit the activity of actin capping protein at the barbed ends of actin filaments.	SIGNOR-135422
P19174	P00533	0	phosphorylation	up-regulates	0.841	We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation.	SIGNOR-20984
Q9NXA8	P11413	1	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
O00444	Q9UPN4	1	phosphorylation	up-regulates activity	0.534	We conclude that PLK4 phosphorylates CEP131 at Ser 78 to maintains centriolar satellite integrity.	SIGNOR-280075
P23352	Q12857	0	transcriptional regulation	down-regulates quantity	0.2	By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development	SIGNOR-268872
Q9NRC8	Q13131	0	phosphorylation	down-regulates quantity by destabilization	0.2	Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.\|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ.	SIGNOR-275864
P37088	Q96PU5	0	ubiquitination	down-regulates quantity by destabilization	0.775	The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane.	SIGNOR-251948
Q13976	Q13507	1	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142961
Q13131	Q9H2X6	1	phosphorylation	up-regulates activity	0.2	These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J).	SIGNOR-276469
A7KAX9	P04629	0	relocalization	up-regulates	0.602	Grit translocation was regulated by receptor stimulation	SIGNOR-95809
P54132	Q8IYW5	0	ubiquitination	up-regulates activity	0.262	Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.	SIGNOR-272114
P23760	P22455	1	transcriptional regulation	up-regulates quantity by expression	0.365	FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS.	SIGNOR-251572
Q9HBA0	P06241	0	phosphorylation	up-regulates activity	0.35	ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.\|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .	SIGNOR-279991
P84022	Q96PU5	0	ubiquitination	down-regulates activity	0.805	Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation	SIGNOR-232104
Q13976	P50552	1	phosphorylation	down-regulates activity	0.735	Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts	SIGNOR-268289
Q14896	P22612	0	phosphorylation	up-regulates	0.275	Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).	SIGNOR-163788
Q05397	O75962	1	phosphorylation	up-regulates activity	0.509	A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity.	SIGNOR-249188
P45983	Q96FI4	1	phosphorylation	up-regulates activity	0.2	These data confirm that NEIL1 can be phosphorylated by JNK1 in vitro at S207, S306, and S61.	SIGNOR-278315
P28906	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.263	Activation of the CD34 promoter by Sp1 requires the presence of a binding domain at -48 bp as well as the 5' untranslated region, which also binds Sp1	SIGNOR-241481
P05412	Q96KB5	0	phosphorylation	up-regulates activity	0.43	TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun.\|These data confirm the phosphorylation of c-Jun by TOPK at serine 63 and 73 during the development of resistance to EGFR-targeted TKIs.	SIGNOR-278156
Q08881	P42680	1	phosphorylation	up-regulates	0.407	Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated	SIGNOR-98090
Q96EB6	P42345	0	phosphorylation	down-regulates activity	0.551	These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent squamous cell carcinoma cells via Bfl-1/A1 in the absence of functional p53.\|This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1.	SIGNOR-280047
P18848	O75807	1	transcriptional regulation	up-regulates quantity by expression	0.657	ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.	SIGNOR-260172
Q9BXW9	Q9NW38	0	ubiquitination	up-regulates activity	0.9	Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo	SIGNOR-263250
P07948	O15492	1	phosphorylation	up-regulates activity	0.346	Lyn kinase phosphorylated recombinant RGS16 in vitro. Induction of RGS16 tyrosine phosphorylation was associated with increased RGS16 protein levels and enhanced GAP activity in cell membranes.	SIGNOR-251410
P35354	Q14934	0	transcriptional regulation	up-regulates quantity by expression	0.282	NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration	SIGNOR-264027
Q13950	P49841	0	phosphorylation	down-regulates activity	0.301	Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.\|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ).	SIGNOR-279051
Q9NX95	Q16623	1	relocalization	up-regulates activity	0.421	Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.	SIGNOR-264812
P29375	P31749	0	phosphorylation	up-regulates activity	0.303	We immunoprecipitated ectopically expressed wild-type KDM5A or KDM5Amut5A and performed an in vitro kinase assay using recombinant AKT1 in the presence or absence of AKT inhibition.Wild-type KDM5A is phosphorylated by AKT1 and this modification is sensitive to AKT inhibition, whereas KDM5Amut5A is not phosphorylated in the presence of AKT1 (Figure 3C).These results suggest that AKT-mediated KDM5A phosphorylation enhances KDM5A promoter recruitment.	SIGNOR-274062
O75385	Q9C0C7	1	phosphorylation	up-regulates	0.695	When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation.	SIGNOR-168292
P00519	P56962	1	phosphorylation	down-regulates activity	0.2	C-Abl was identified as one of the kinases, which phosphorylates syntaxin 17.Western blot shows phosphorylation of syntaxin 17 on Tyr-156 by overexpression and activation of c-Abl. A phospho-mimicking mutant (Y156E) of syntaxin 17 showed reduced interaction with COPI vesicles. These results suggest that tyrosine phosphorylation of syntaxin 17 is likely to have a role in regulating syntaxin 17 dependent membrane trafficking in the early secretory pathway.	SIGNOR-273538
Q7L2J0	Q6NYC1	0	cleavage	down-regulates activity	0.268	JMJD6 cleaves MePCE. we propose that JMJD6 is the cognate protease of MePCE and cleaves at the R171 site within MePCE. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II.	SIGNOR-261037
Q00610	P12931	0	phosphorylation	up-regulates	0.406	Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling	SIGNOR-65714
P35398	O00327	1	transcriptional regulation	up-regulates quantity by expression	0.689	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-267982
Q13202	Q16539	1	dephosphorylation	down-regulates	0.591	M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk	SIGNOR-199695
Q9Y2I6	P53350	0	phosphorylation	down-regulates activity	0.7	Here, we identify a centrosomal plk1 substrate, termed nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates nlp and disrupts both its centrosome association and its gamma-tubulin interaction	SIGNOR-103356
Q9UQC2	P28482	0	phosphorylation	up-regulates	0.68	Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623.	SIGNOR-128727
Q16595	Q9BV68	0	ubiquitination	down-regulates quantity by destabilization	0.385	Depletion of RNF126 by specific small interfering RNA delays the degradation of frataxin precursor and increases its stability.\|Here we report on the identification of really interesting new gene finger protein 126 (RNF126) as the E3 ligase that ubiquitinates frataxin.	SIGNOR-278663
P27361	O43521	1	phosphorylation	down-regulates quantity by destabilization	0.731	In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel	SIGNOR-129878
P30291	O14757	0	phosphorylation	up-regulates	0.611	Chk1 also phosphorylates and stabilizes wee1.	SIGNOR-163164
O14595	Q15797	1	dephosphorylation	down-regulates	0.5	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-148434
Q9Y625	O95644	0	transcriptional regulation	up-regulates quantity by expression	0.251	NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.	SIGNOR-264022
Q02224	O43683	0	relocalization	up-regulates activity	0.831	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252016
P51608	P16220	1	post transcriptional regulation	up-regulates quantity by expression	0.531	Interestingly, Creb1 was one of the activated MeCP2 targets that we validated by quantitative real-time RT-PCR (Fig. 1C), and using ChIP analysis we found that in vivo MeCP2 binds to the promoter region of Creb1, with significantly enhanced binding in MECP2-Tg samples compared to WT (p < 0.05) \| In addition, Sst and CREB1 protein levels were increased in MECP2-Tg hypothalami compared to WT, indicating that MeCP2 indeed enhances expression of Sst and Creb1	SIGNOR-264682
P19634	P28482	0	phosphorylation	up-regulates	0.669	We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo.	SIGNOR-151925
P43403	P23470	0	dephosphorylation	up-regulates activity	0.26	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-254733
Q01973	P21860	1	phosphorylation	up-regulates activity	0.343	Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.\|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells.	SIGNOR-279279
O15297	P13051	1	dephosphorylation	down-regulates activity	0.377	PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.\|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases.	SIGNOR-277156
Q9UHD2	P56962	1	phosphorylation	up-regulates activity	0.291	Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202.	SIGNOR-273812
P15311	Q9P289	0	phosphorylation	up-regulates	0.2	Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. Mst4 phosphorylates the regulatory t567 residue of ezrin.	SIGNOR-185563
O15297	P53778	1	dephosphorylation	down-regulates	0.297	Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180.	SIGNOR-135976
Q15672	P53671	0	phosphorylation	up-regulates quantity	0.2	LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).\|LIMK2 positively regulates TWIST1 protein levels.	SIGNOR-278952
P46940	Q8IVH8	0	phosphorylation	up-regulates activity	0.2	GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration.	SIGNOR-277479
P06493	Q15116	1	phosphorylation	down-regulates quantity by destabilization	0.2	We demonstrated that cyclin-dependent kinase 1-mediated phosphorylation of Ser261 residue primes PD-1 protein nucleus translocation and binding with FBW7.	SIGNOR-277605
O43561	Q9H093	0	phosphorylation	down-regulates activity	0.2	Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).\|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.	SIGNOR-280052
P27361	P04049	1	phosphorylation	down-regulates activity	0.637	Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. \| Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.\|FLAG-Raf-1 phosphorylated by activated ERK2	SIGNOR-143688
Q9H2X6	P17096	1	phosphorylation	down-regulates	0.493	Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.	SIGNOR-158620
Q9H0K1	O75581	1	phosphorylation	up-regulates activity	0.2	Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation.	SIGNOR-275399
Q7Z5H3	P60953	1	gtpase-activating protein	down-regulates activity	0.543	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-260478
Q16829	P10912	1	dephosphorylation	down-regulates	0.313	Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor.	SIGNOR-104545
Q13882	P23246	1	phosphorylation	down-regulates activity	0.531	BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.\|These data suggest that BRK activity impedes the ability of PSF to bind RNA.To map the PSF tyrosine residues phosphorylated by BRK and assess if the PSF N-terminal is required for phosphorylation, we co-transfected HEK293 cells with various GFP-PSF deletion mutants in the presence or absence myc-BRK-YF.	SIGNOR-279754
P48729	Q6IE81	1	phosphorylation	down-regulates activity	0.277	We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling.	SIGNOR-273618
O75553	P23470	0	dephosphorylation	down-regulates activity	0.2	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-254697
P06493	Q14674	1	phosphorylation	down-regulates	0.572	Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro	SIGNOR-113126
Q05655	O15162	1	phosphorylation	up-regulates	0.424	Following the induction of apoptosis, however, phosphorylation of serine residues decreased and it increased on threonine, consistent with the predicted pkc phosphorylation site at thr-161. Transfection of cho cells with scramblase and pkc_, but not scramblase or pkc_ alone, increased scramblase activity	SIGNOR-76904
Q13131	P00390	1	phosphorylation	up-regulates activity	0.288	Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity.	SIGNOR-273734
O43150	P84077	1	gtpase-activating protein	up-regulates activity	0.655	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-269705
O95433	P00519	0	phosphorylation	up-regulates activity	0.251	Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity	SIGNOR-260938
O95235	P53350	0	phosphorylation	up-regulates activity	0.761	MKlp2 treated with Plk1 did not form the regular microtubule bundles seen with MKlp2 only; many single microtubules were seen instead, and the bundles that were formed were loose parallel arrays rather than the dense bundles seen with untreated MKlp2.\|We propose that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis.	SIGNOR-278201
Q05086	Q14160	1	polyubiquitination	down-regulates quantity by destabilization	0.552	Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase	SIGNOR-272573
Q06124	P43405	1	dephosphorylation	down-regulates activity	0.545	Another SHP isoform, SHP-2, has been linked to negative regulation of Syk.\|Syk and LAT are differentially dephosphorylated by SHP-2 and SHP-1, respectively.	SIGNOR-277085
Q16236	P13640	1	transcriptional regulation	up-regulates quantity by expression	0.286	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In the context of cancer, particularly HCC, the upregulation of MT1G has been linked to resistance against sorafenib, a kinase inhibitor commonly used in cancer therapy	SIGNOR-279866
Q9UBK2	Q16539	0	phosphorylation	up-regulates	0.586	Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298	SIGNOR-112774
Q16612	Q02156	0	phosphorylation	down-regulates quantity by destabilization	0.2	Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.	SIGNOR-273830
P27695	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Based on these results, we conclude that Parkin directly ubiquitinates APE1.\|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress.	SIGNOR-278531
P35354	P59595	0	transcriptional regulation	up-regulates activity	0.2	SARS-CoV N protein activates COX-2 promoter and induces COX-2 protein expression	SIGNOR-262314
Q04759	P06241	0	phosphorylation	up-regulates	0.344	Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.	SIGNOR-68798
Q8IXL6	P23327	1	phosphorylation	up-regulates activity	0.404	Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.	SIGNOR-273639
P54259	P45984	0	phosphorylation	down-regulates activity	0.2	Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,	SIGNOR-102402
O75914	Q99523	1	phosphorylation	down-regulates activity	0.2	PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.	SIGNOR-273719
P30041	P28482	0	phosphorylation	up-regulates	0.693	These results show that the mapks can mediate phosphorylation of prdx6 at thr-177 with a consequent marked increase in its aipla(2) activity.	SIGNOR-183379
Q13535	P35790	1	phosphorylation	up-regulates activity	0.248	In particular, ATR phosphorylates Chk 1 and ATM signals to Chk 2.	SIGNOR-280184
P06493	P50613	0	phosphorylation	up-regulates	0.581	The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues	SIGNOR-38307
Q16611	O95831	1	relocalization	up-regulates	0.297	First, bax/bak-mediated momp leads to the release of a significant part of the cyt c, smac/diablo and htra2/omi proteins. in a third step, cyt c, smac/diablo and htra2/omi, which were released into the cytosol, trigger caspase activation. This is necessary to alter the physical association of aif and endog with the im to enable their relocation to the cytosol.	SIGNOR-192092
P06493	Q9H1A4	1	phosphorylation	up-regulates	0.592	Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation	SIGNOR-119705
P08047	Q9UKX5	1	null	up-regulates quantity by expression	0.2	We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.	SIGNOR-253350
Q9NP70	Q8IXL6	0	phosphorylation	up-regulates activity	0.664	Disruption of Fam20C completely eliminated AMBN phosphorylation, suggesting that Fam20C is the kinase that phosphorylates enamel matrix proteins in vivo (XREF_FIG).	SIGNOR-280010
Q9UHV7	Q969H0	0	ubiquitination	down-regulates quantity by destabilization	0.371	The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.	SIGNOR-266690
P06239	P06127	1	phosphorylation	up-regulates activity	0.541	Tyrosine phosphorylation of cd5 requires lck activity. We propose that t cell activation mediates cd5 tyrosine phosphorylation at residues y429 and y463 mainly through the activation of lck	SIGNOR-106799
P60953	O94989	0	guanine nucleotide exchange factor	up-regulates activity	0.556	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-260541
Q16512	P10636	1	phosphorylation	down-regulates	0.329	Phosphorylation of tau is regulated by pknthere is a pkn-specific phosphorylation site, ser-320, in mbdsthus pkn serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.	SIGNOR-84958

P46937

O00506

0

phosphorylation

up-regulates activity

0.265

Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.

SIGNOR-278993

Q2NKX8

P53350

0

relocalization

up-regulates

0.88

Human pich was identified as an interaction partner and substrate of plk1. Our data indicate that plk1 prevents the association of pich with chromosome arms and restricts its localization to the kt/centromere region

SIGNOR-152136

Q9H3D4

Q6ZMZ3

1

transcriptional regulation

up-regulates quantity by expression

0.2

Here we show that in the developing skin, epidermal progenitor cells of mice lacking p63 transcription factor display alterations in the nuclear shape accompanied by a marked decrease in expression of several nuclear envelope-associated components (Lamin B1, Lamin A/C, Sun1, Nesprin-3, Plectin) compared with controls. Furthermore, chromatin immunoprecipitation-quantitative PCR assay showed enrichment of p63 on Sun1, Syne3, and Plec promoters, suggesting them as p63 targets.

SIGNOR-263280

O43524

O15111

0

phosphorylation

down-regulates

0.572

Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. The tnf treatment of ht-29 cells increased ikk-dependent foxo3 ser644 phosphorylation.

SIGNOR-124203

Q93079

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265391

P27361

Q9H9S0

1

phosphorylation

down-regulates

0.492

We found that activation of ERK1 signaling inhibited transactivation activity of Nanog.|We showed the direct phosphorylation of Nanog by ERK1 and clearly showed that Ser52 is the major phosphorylation site and Ser65 is weakly phosphorylated by ERK1.

SIGNOR-278487

P04629

P06241

0

phosphorylation

up-regulates activity

0.254

Here, we demonstrate that Fyn can directly phosphorylate the intracellular domain of TrkA and that its kinase activity towards Trk is increased by GPCR stimulation ( Fig. 4 ).

SIGNOR-279410

P51812

Q9H6Z4

1

phosphorylation

up-regulates quantity

0.328

RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran

SIGNOR-276148

P24941

Q14106

1

phosphorylation

up-regulates activity

0.246

Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.

SIGNOR-273601

P68400

P52907

1

phosphorylation

up-regulates

0.2

We demonstrate that ser9 of cpalpha is phosphorylated by protein kinase ck2 in vitro, that cpalpha is phosphorylated in vivo. Finally, we demonstrate that ckip-1 and ck2 inhibit the activity of actin capping protein at the barbed ends of actin filaments.

SIGNOR-135422

P19174

P00533

0

phosphorylation

up-regulates

0.841

We have identified the sites phosphorylated in vitro by epidermal growth factor (egf) receptor kinase in bovine brain phospholipase c-gamma (plc-gamma). They are tyrosine residues 472, 771, 783, and 1254. we propose, therefore, that the phosphorylation of plc-gamma by egf receptor kinase alters its interaction with putative inhibitory proteins and leads to its activation.

SIGNOR-20984

Q9NXA8

P11413

1

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

O00444

Q9UPN4

1

phosphorylation

up-regulates activity

0.534

We conclude that PLK4 phosphorylates CEP131 at Ser 78 to maintains centriolar satellite integrity.

SIGNOR-280075

P23352

Q12857

0

transcriptional regulation

down-regulates quantity

0.2

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

SIGNOR-268872

Q9NRC8

Q13131

0

phosphorylation

down-regulates quantity by destabilization

0.2

Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.|These results strongly suggest that the phosphorylation status of SirT7 at T153 plays a crucial role in determining its subcellular distribution, degradation and binding to REGγ.

SIGNOR-275864

P37088

Q96PU5

0

ubiquitination

down-regulates quantity by destabilization

0.775

The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane.

SIGNOR-251948

Q13976

Q13507

1

phosphorylation

down-regulates

0.408

The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.

SIGNOR-142961

Q13131

Q9H2X6

1

phosphorylation

up-regulates activity

0.2

These results indicate that HIPK2 is a substrate of AMPKα2 in vitro and in vivo. Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKα2 in vitro (Figure S5J).

SIGNOR-276469

A7KAX9

P04629

0

relocalization

up-regulates

0.602

Grit translocation was regulated by receptor stimulation

SIGNOR-95809

P54132

Q8IYW5

0

ubiquitination

up-regulates activity

0.262

Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80.

SIGNOR-272114

P23760

P22455

1

transcriptional regulation

up-regulates quantity by expression

0.365

FGFR4 is a transcriptional target of PAX3 and the PAX3-FOXO1 fusion protein found in ARMS.

SIGNOR-251572

Q9HBA0

P06241

0

phosphorylation

up-regulates activity

0.35

ROS could be detected by Fyn, which is required to activate TRPV4 in a redox-sensitive manner.|The Ca 2+ response to H 2 O 2 required the basal phosphorylation of TRPV4 by the Src kinase Fyn, which may serve as the redox sensor responsible for TRPV4 activation (Figure 2 ) [220] , and was able to increase barrier permeability [219] .

SIGNOR-279991

P84022

Q96PU5

0

ubiquitination

down-regulates activity

0.805

Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation

SIGNOR-232104

Q13976

P50552

1

phosphorylation

down-regulates activity

0.735

Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts

SIGNOR-268289

Q14896

P22612

0

phosphorylation

up-regulates

0.275

Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).

SIGNOR-163788

Q05397

O75962

1

phosphorylation

up-regulates activity

0.509

A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity.

SIGNOR-249188

P45983

Q96FI4

1

phosphorylation

up-regulates activity

0.2

These data confirm that NEIL1 can be phosphorylated by JNK1 in vitro at S207, S306, and S61.

SIGNOR-278315

P28906

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.263

Activation of the CD34 promoter by Sp1 requires the presence of a binding domain at -48 bp as well as the 5' untranslated region, which also binds Sp1

SIGNOR-241481

P05412

Q96KB5

0

phosphorylation

up-regulates activity

0.43

TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun.|These data confirm the phosphorylation of c-Jun by TOPK at serine 63 and 73 during the development of resistance to EGFR-targeted TKIs.

SIGNOR-278156

Q08881

P42680

1

phosphorylation

up-regulates

0.407

Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated

SIGNOR-98090

Q96EB6

P42345

0

phosphorylation

down-regulates activity

0.551

These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent squamous cell carcinoma cells via Bfl-1/A1 in the absence of functional p53.|This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1.

SIGNOR-280047

P18848

O75807

1

transcriptional regulation

up-regulates quantity by expression

0.657

ATF4 also induces another bZIP protein C/EBP-homologous protein (CHOP), which is responsible for triggering apoptosis in cells under prolonged ER stress. ATF4 and CHOP further induce growth arrest and DNA damage–inducible protein 34 (GADD34),a regulatory subunit of protein phosphatase 1 (PP1) that dephosphorylates eIF2α. This negative feedback mechanism enables protein synthesis to resume after resolution of ER stress.

SIGNOR-260172

Q9BXW9

Q9NW38

0

ubiquitination

up-regulates activity

0.9

Thus, eight of the nine components of the FA core complex are FA proteins (FANC‐A, B, C, E, F, G, L, and M). Furthermore, two of the newly discovered FA proteins have enzymatic activities: FANCL is a ubiquitin ligase essential for FANCD2 monoubiquitination in vivo

SIGNOR-263250

P07948

O15492

1

phosphorylation

up-regulates activity

0.346

Lyn kinase phosphorylated recombinant RGS16 in vitro. Induction of RGS16 tyrosine phosphorylation was associated with increased RGS16 protein levels and enhanced GAP activity in cell membranes.

SIGNOR-251410

P35354

Q14934

0

transcriptional regulation

up-regulates quantity by expression

0.282

NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration

SIGNOR-264027

Q13950

P49841

0

phosphorylation

down-regulates activity

0.301

Collectively, these data demonstrate that the kinase activity of GSK-3beta suppresses the Runx2 transcriptional activity.|In vitro kinase assay confirmed that the Runx2 phosphorylation by GSK-3\u03b2 was reduced by the S369-S373-S377 mutation ( xref ).

SIGNOR-279051

Q9NX95

Q16623

1

relocalization

up-regulates activity

0.421

Conventional kinesin I heavy chain binds to syntabulin and associates with syntabulin-linked syntaxin vesicles in vivo. These findings suggest that syntabulin functions as a linker molecule that attaches syntaxin-cargo vesicles to kinesin I, enabling the transport of syntaxin-1 to neuronal processes.

SIGNOR-264812

P29375

P31749

0

phosphorylation

up-regulates activity

0.303

We immunoprecipitated ectopically expressed wild-type KDM5A or KDM5Amut5A and performed an in vitro kinase assay using recombinant AKT1 in the presence or absence of AKT inhibition.Wild-type KDM5A is phosphorylated by AKT1 and this modification is sensitive to AKT inhibition, whereas KDM5Amut5A is not phosphorylated in the presence of AKT1 (Figure 3C).These results suggest that AKT-mediated KDM5A phosphorylation enhances KDM5A promoter recruitment.

SIGNOR-274062

O75385

Q9C0C7

1

phosphorylation

up-regulates

0.695

When autophagy is induced, ulk1 phosphorylates ambra1, releasing the autophagy core complex from dynein. Its subsequent relocalization to the endoplasmic reticulum enables autophagosome nucleation. Ambra1-dlc1 dissociates from the dynein complex upon ulk1-dependent ambra1 phosphorylation.

SIGNOR-168292

P00519

P56962

1

phosphorylation

down-regulates activity

0.2

C-Abl was identified as one of the kinases, which phosphorylates syntaxin 17.Western blot shows phosphorylation of syntaxin 17 on Tyr-156 by overexpression and activation of c-Abl. A phospho-mimicking mutant (Y156E) of syntaxin 17 showed reduced interaction with COPI vesicles. These results suggest that tyrosine phosphorylation of syntaxin 17 is likely to have a role in regulating syntaxin 17 dependent membrane trafficking in the early secretory pathway.

SIGNOR-273538

Q7L2J0

Q6NYC1

0

cleavage

down-regulates activity

0.268

JMJD6 cleaves MePCE. we propose that JMJD6 is the cognate protease of MePCE and cleaves at the R171 site within MePCE. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II.

SIGNOR-261037

Q00610

P12931

0

phosphorylation

up-regulates

0.406

Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling

SIGNOR-65714

P35398

O00327

1

transcriptional regulation

up-regulates quantity by expression

0.689

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-267982

Q13202

Q16539

1

dephosphorylation

down-regulates

0.591

M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk

SIGNOR-199695

Q9Y2I6

P53350

0

phosphorylation

down-regulates activity

0.7

Here, we identify a centrosomal plk1 substrate, termed nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates nlp and disrupts both its centrosome association and its gamma-tubulin interaction

SIGNOR-103356

Q9UQC2

P28482

0

phosphorylation

up-regulates

0.68

Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623.

SIGNOR-128727

Q16595

Q9BV68

0

ubiquitination

down-regulates quantity by destabilization

0.385

Depletion of RNF126 by specific small interfering RNA delays the degradation of frataxin precursor and increases its stability.|Here we report on the identification of really interesting new gene finger protein 126 (RNF126) as the E3 ligase that ubiquitinates frataxin.

SIGNOR-278663

P27361

O43521

1

phosphorylation

down-regulates quantity by destabilization

0.731

In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel

SIGNOR-129878

P30291

O14757

0

phosphorylation

up-regulates

0.611

Chk1 also phosphorylates and stabilizes wee1.

SIGNOR-163164

O14595

Q15797

1

dephosphorylation

down-regulates

0.5

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-148434

Q9Y625

O95644

0

transcriptional regulation

up-regulates quantity by expression

0.251

NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype.

SIGNOR-264022

Q02224

O43683

0

relocalization

up-regulates activity

0.831

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252016

P51608

P16220

1

post transcriptional regulation

up-regulates quantity by expression

0.531

Interestingly, Creb1 was one of the activated MeCP2 targets that we validated by quantitative real-time RT-PCR (Fig. 1C), and using ChIP analysis we found that in vivo MeCP2 binds to the promoter region of Creb1, with significantly enhanced binding in MECP2-Tg samples compared to WT (p < 0.05) | In addition, Sst and CREB1 protein levels were increased in MECP2-Tg hypothalami compared to WT, indicating that MeCP2 indeed enhances expression of Sst and Creb1

SIGNOR-264682

P19634

P28482

0

phosphorylation

up-regulates

0.669

We have demonstrated that the map kinases extracellular signal-regulated kinases 1 and 2 (erk1/2) are implicated in growth factor activation of nhe1. / our results suggest that amino acids ser770 and ser771 mediate erk-dependent activation of the na+/h+ exchanger in vivo.

SIGNOR-151925

P43403

P23470

0

dephosphorylation

up-regulates activity

0.26

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-254733

Q01973

P21860

1

phosphorylation

up-regulates activity

0.343

Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells.

SIGNOR-279279

O15297

P13051

1

dephosphorylation

down-regulates activity

0.377

PPM1D dephosphorylation of UNG2 is correlated with reduced UNG2 activity on uracil-containing templates.|This result suggests that PPM1D specifically inhibits UNG2 and not other uracil DNA glycosylases.

SIGNOR-277156

Q9UHD2

P56962

1

phosphorylation

up-regulates activity

0.291

Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202.

SIGNOR-273812

P15311

Q9P289

0

phosphorylation

up-regulates

0.2

Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. Mst4 phosphorylates the regulatory t567 residue of ezrin.

SIGNOR-185563

O15297

P53778

1

dephosphorylation

down-regulates

0.297

Ppm1d selectively inhibits p38 activation by dephosphorylating thr 180.

SIGNOR-135976

Q15672

P53671

0

phosphorylation

up-regulates quantity

0.2

LIMK2 directly phosphorylated TWIST1, indicating that LIMK2 also regulates TWIST1 post-translationally (XREF_FIG).|LIMK2 positively regulates TWIST1 protein levels.

SIGNOR-278952

P46940

Q8IVH8

0

phosphorylation

up-regulates activity

0.2

GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration.

SIGNOR-277479

P06493

Q15116

1

phosphorylation

down-regulates quantity by destabilization

0.2

We demonstrated that cyclin-dependent kinase 1-mediated phosphorylation of Ser261 residue primes PD-1 protein nucleus translocation and binding with FBW7.

SIGNOR-277605

O43561

Q9H093

0

phosphorylation

down-regulates activity

0.2

Analysis by an in vitro kinase assay revealed that NUAK2 could phosphorylate immunoprecipitated LATS and that this phosphorylation was lost in the LATS double mutant (DM), T246A/S613A (Fig.\u00a0 xref ).|We showed that phosphorylation of Ser613, located upstream of the KD, adjacent to the MOB binding site and to a lesser extent the N-terminal localized T246, are required for NUAK2 to inhibit LATS.

SIGNOR-280052

P27361

P04049

1

phosphorylation

down-regulates activity

0.637

Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2

SIGNOR-143688

Q9H2X6

P17096

1

phosphorylation

down-regulates

0.493

Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.

SIGNOR-158620

Q9H0K1

O75581

1

phosphorylation

up-regulates activity

0.2

Mechanistically, SIK2, phosphorylated by CK1α, directly phosphorylated LRP6 in a SIK2 kinase activity-dependent manner, leading to Wnt/β-catenin signaling pathway activation.

SIGNOR-275399

Q7Z5H3

P60953

1

gtpase-activating protein

down-regulates activity

0.543

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-260478

Q16829

P10912

1

dephosphorylation

down-regulates

0.313

Identification of protein tyrosine phosphatases with specificity for the ligand-activated growth hormone receptor.

SIGNOR-104545

Q13882

P23246

1

phosphorylation

down-regulates activity

0.531

BRK phosphorylates PSF promoting its cytoplasmic localization and cell cycle arrest.|These data suggest that BRK activity impedes the ability of PSF to bind RNA.To map the PSF tyrosine residues phosphorylated by BRK and assess if the PSF N-terminal is required for phosphorylation, we co-transfected HEK293 cells with various GFP-PSF deletion mutants in the presence or absence myc-BRK-YF.

SIGNOR-279754

P48729

Q6IE81

1

phosphorylation

down-regulates activity

0.277

We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling.

SIGNOR-273618

O75553

P23470

0

dephosphorylation

down-regulates activity

0.2

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-254697

P06493

Q14674

1

phosphorylation

down-regulates

0.572

Both cdc2/cyclinb1 and mapk (erk2) efficiently phosphorylate separase at its major inhibitory site in vitro

SIGNOR-113126

Q05655

O15162

1

phosphorylation

up-regulates

0.424

Following the induction of apoptosis, however, phosphorylation of serine residues decreased and it increased on threonine, consistent with the predicted pkc phosphorylation site at thr-161. Transfection of cho cells with scramblase and pkc_, but not scramblase or pkc_ alone, increased scramblase activity

SIGNOR-76904

Q13131

P00390

1

phosphorylation

up-regulates activity

0.288

Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity.

SIGNOR-273734

O43150

P84077

1

gtpase-activating protein

up-regulates activity

0.655

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-269705

O95433

P00519

0

phosphorylation

up-regulates activity

0.251

Here, we show that c-Abl kinase phosphorylates Y223 in human Aha1 (hAha1), promoting its interaction with Hsp90. This, consequently, results in an increased Hsp90 ATPase activity

SIGNOR-260938

O95235

P53350

0

phosphorylation

up-regulates activity

0.761

MKlp2 treated with Plk1 did not form the regular microtubule bundles seen with MKlp2 only; many single microtubules were seen instead, and the bundles that were formed were loose parallel arrays rather than the dense bundles seen with untreated MKlp2.|We propose that phosphorylation of MKlp2 by Plk1 is necessary for the spatial restriction of Plk1 to the central spindle during anaphase and telophase, and the complex of these two proteins is required for cytokinesis.

SIGNOR-278201

Q05086

Q14160

1

polyubiquitination

down-regulates quantity by destabilization

0.552

Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase

SIGNOR-272573

Q06124

P43405

1

dephosphorylation

down-regulates activity

0.545

Another SHP isoform, SHP-2, has been linked to negative regulation of Syk.|Syk and LAT are differentially dephosphorylated by SHP-2 and SHP-1, respectively.

SIGNOR-277085

Q16236

P13640

1

transcriptional regulation

up-regulates quantity by expression

0.286

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification. The expression of MT1G during ferroptosis is regulated by the NFE2L2 signaling pathway. In the context of cancer, particularly HCC, the upregulation of MT1G has been linked to resistance against sorafenib, a kinase inhibitor commonly used in cancer therapy

SIGNOR-279866

Q9UBK2

Q16539

0

phosphorylation

up-regulates

0.586

Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298

SIGNOR-112774

Q16612

Q02156

0

phosphorylation

down-regulates quantity by destabilization

0.2

Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.

SIGNOR-273830

P27695

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Based on these results, we conclude that Parkin directly ubiquitinates APE1.|These results indicated that degradation of APE1 by Parkin was limited compared to the transiently expressed APE1, suggesting that a large portion of APE1 is not in contact with the Parkin and PINK1 without induction of stresses such as oxidative stress.

SIGNOR-278531

P35354

P59595

0

transcriptional regulation

up-regulates activity

0.2

SARS-CoV N protein activates COX-2 promoter and induces COX-2 protein expression

SIGNOR-262314

Q04759

P06241

0

phosphorylation

up-regulates

0.344

Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.

SIGNOR-68798

Q8IXL6

P23327

1

phosphorylation

up-regulates activity

0.404

Here, we demonstrate that family with sequence similarity 20C (Fam20C), a recently characterized protein kinase in the secretory pathway, phosphorylates HRC on Ser96. HRC Ser96 phosphorylation was confirmed in cells and human hearts.The pSer96-HRC binds tighter to triadin than S96A-HRC, which cannot be phosphorylated. Conversely, S96A-HRC or unphosphorylated Ser96-HRC binds tighter to SERCA2a. This suggests that Ser96-HRC phosphorylation (P) regulates HRC’s interactions with the major SR Ca-cycling proteins.

SIGNOR-273639

P54259

P45984

0

phosphorylation

down-regulates activity

0.2

Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment,

SIGNOR-102402

O75914

Q99523

1

phosphorylation

down-regulates activity

0.2

PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.

SIGNOR-273719

P30041

P28482

0

phosphorylation

up-regulates

0.693

These results show that the mapks can mediate phosphorylation of prdx6 at thr-177 with a consequent marked increase in its aipla(2) activity.

SIGNOR-183379

Q13535

P35790

1

phosphorylation

up-regulates activity

0.248

In particular, ATR phosphorylates Chk 1 and ATM signals to Chk 2.

SIGNOR-280184

P06493

P50613

0

phosphorylation

up-regulates

0.581

The mo15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (cdks) through phosphorylation of thr161 and its homologues

SIGNOR-38307

Q16611

O95831

1

relocalization

up-regulates

0.297

First, bax/bak-mediated momp leads to the release of a significant part of the cyt c, smac/diablo and htra2/omi proteins. in a third step, cyt c, smac/diablo and htra2/omi, which were released into the cytosol, trigger caspase activation. This is necessary to alter the physical association of aif and endog with the im to enable their relocation to the cytosol.

SIGNOR-192092

P06493

Q9H1A4

1

phosphorylation

up-regulates

0.592

Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation

SIGNOR-119705

P08047

Q9UKX5

1

null

up-regulates quantity by expression

0.2

We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.

SIGNOR-253350

Q9NP70

Q8IXL6

0

phosphorylation

up-regulates activity

0.664

Disruption of Fam20C completely eliminated AMBN phosphorylation, suggesting that Fam20C is the kinase that phosphorylates enamel matrix proteins in vivo (XREF_FIG).

SIGNOR-280010

Q9UHV7

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.371

The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association.

SIGNOR-266690

P06239

P06127

1

phosphorylation

up-regulates activity

0.541

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

SIGNOR-106799

P60953

O94989

0

guanine nucleotide exchange factor

up-regulates activity

0.556

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-260541

Q16512

P10636

1

phosphorylation

down-regulates

0.329

Phosphorylation of tau is regulated by pknthere is a pkn-specific phosphorylation site, ser-320, in mbdsthus pkn serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

SIGNOR-84958