GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q9UQM7	Q9Y4D2	1	phosphorylation	down-regulates activity	0.2	Activated CaMKII interacted with the C-terminal domain of DGLalpha, phosphorylated two serine residues and inhibited DGLalpha activity. \|CaMKIIalpha phosphorylates DGLalpha at Ser808 and Ser782	SIGNOR-275540
Q9NS23	Q96GD4	0	phosphorylation	down-regulates	0.438	Here, we show that aurora a and b associate with and phosphorylate rassf1a on serine 203 aurora a regulates prometaphase progression by inhibiting the ability of rassf1a to suppress apc-cdc20 activity.	SIGNOR-184561
Q07954	P12931	0	phosphorylation	up-regulates activity	0.394	We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras	SIGNOR-101535
Q99801	Q9Y463	0	phosphorylation	down-regulates quantity by destabilization	0.332	In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover.	SIGNOR-279610
O14965	Q9NS23	1	phosphorylation	down-regulates	0.448	Aurora-a appears to phosphorylate rassf1a at threonine202 and/or serine203 that reside within the known microtubule-binding domain of rassf1a. Substitutions of these residues with glutamic acid at both positions, mimicking constitutive phosphorylation of rassf1a, disrupt rassf1a interactions with microtubules and abolish its ability to induce m-phase cell cycle arrest.	SIGNOR-155815
Q12778	P06493	0	phosphorylation	down-regulates	0.511	Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1.	SIGNOR-178202
Q8IYW5	Q14669	0	ubiquitination	down-regulates activity	0.465	Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.	SIGNOR-266783
P28482	Q86UC2	1	phosphorylation	up-regulates activity	0.2	ERK1/2 phosphorylate RSPH3. the extent of radiolabeled phosphate incorporation into RSPH3 T286A was much less than that into wild-type RSPH3, suggesting that threonine 286 is the major ERK1/2 phosphorylation site in cells. ERK2 also phosphorylates RSPH3 on threonine 243 to a lesser extent. Phosphorylation of the double mutant T243V/T286A RSPH3 was no more than 20% that of wild-type RSPH3 (Fig. 4, C and D). inhibiting ERK1/2 activity appears to negatively regulate the AKAP function of RSPH3.	SIGNOR-262839
Q9HC98	O96017	0	phosphorylation	down-regulates activity	0.229	Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro .	SIGNOR-279404
P60510	Q13085	1	dephosphorylation	up-regulates activity	0.242	PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders.	SIGNOR-267724
Q86YT6	Q9UPN4	1	ubiquitination	down-regulates	0.43	We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined.	SIGNOR-272876
P18031	Q9NZJ5	1	dephosphorylation	down-regulates activity	0.267	Finally, we demonstrated that wild-type PTP1B directly dephosphorylated myc-tagged PERK that had been isolated from tunicamycin-treated HEK293T cells by immunoprecipitation ( xref ).\|The ability of PTP1B to dephosphorylate Tyr619 and inactivate PERK is fine tuned by the production of H 2 S by CSE in response to ER stress.	SIGNOR-277051
Q96T68	P68431	1	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263896
O75030	P49840	0	phosphorylation	up-regulates	0.294	Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter	SIGNOR-72878
P53779	O43521	1	phosphorylation	up-regulates activity	0.689	JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.	SIGNOR-250130
P19883	Q13469	0	transcriptional regulation	up-regulates quantity by expression	0.2	MyoD, CREB, and NFAT Mediate the Transcriptional Activation of the Follistatin Promoter Induced by TSA	SIGNOR-251729
P63000	P31749	0	phosphorylation	down-regulates activity	0.725	Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1	SIGNOR-252576
Q13043	P31751	0	phosphorylation	down-regulates	0.262	Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.	SIGNOR-201125
P43004	Q6VVB1	0	ubiquitination	up-regulates activity	0.2	On the contrary, overexpression of the laforin/malin complex promotes the retention of GLT-1 at the plasma membrane.\|This is due to a direct ubiquitination of GLT-1 by laforin and malin and/or to changes in the dynamics of its Nedd4.2-mediated endocytosis, which is assisted by specific adaptors (\u03b1- and \u03b2-arrestins).	SIGNOR-278586
Q16236	Q14145	0	ubiquitination	down-regulates quantity	0.813	Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation	SIGNOR-259335
Q92688	P68400	0	phosphorylation	up-regulates	0.234	Here, we are able to report that casein kinase 2 (ck2) phosphorylates april on residue threonine244 (thr(244)) and demonstrate that the ck2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes cd83 expression in activated jurkat t cells by interfering with the nucleocytoplasmic translocation of cd83 mrna	SIGNOR-183158
Q86YJ5	Q8NHL6	1	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271534
P27361	Q14005	1	phosphorylation	up-regulates	0.266	The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 in antigen receptor-, sdf1alpha- and il-2-activated t cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.	SIGNOR-121856
P35222	Q13554	0	phosphorylation	down-regulates	0.289	Camkii represses transcriptionally active _-catenin to mediate acute ethanol neurodegeneration and can phosphorylate _-catenincamkii can directly phosphorylate _-catenin. Using targeted mutagenesis we identified camkii phosphorylation sites within human _-catenin at t332, t472, and s552.	SIGNOR-202833
Q12888	Q99986	0	phosphorylation	up-regulates	0.399	The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size	SIGNOR-197625
P30405	P31751	0	phosphorylation	up-regulates activity	0.2	In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.	SIGNOR-276875
Q9UBF6	P42574	1	ubiquitination	down-regulates activity	0.2	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271448
P11473	O60315	0	transcriptional regulation	up-regulates quantity by expression	0.2	ZEB, a Krüppel-type transcription factor known to repress the transcription of several genes, binds to two sites within the VDR promoter and activates the transcription of this receptor in a cell-specific manner. Transfection of ZEB into SW620 colon carcinoma cells results in an up-regulation of the expression of endogenous VDR, confirming the role of ZEB in the transcriptional activation of the VDR gene.	SIGNOR-268954
Q9UQL6	Q9Y463	0	phosphorylation	down-regulates activity	0.372	Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279	SIGNOR-235809
Q14289	Q05397	1	phosphorylation	up-regulates	0.524	Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.	SIGNOR-147070
P50281	Q99558	0	phosphorylation	up-regulates activity	0.2	A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).\|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.	SIGNOR-279631
P30304	Q00534	1	dephosphorylation	up-regulates activity	0.704	Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.	SIGNOR-267569
P10415	P62714	0	dephosphorylation	up-regulates activity	0.385	The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.	SIGNOR-248589
P06493	Q9UNZ2	1	phosphorylation	down-regulates activity	0.325	Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes.	SIGNOR-102350
P31749	P04792	1	phosphorylation	down-regulates	0.66	First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.	SIGNOR-252526
P30874	P31629	0	transcriptional regulation	up-regulates quantity by expression	0.411	Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.	SIGNOR-261617
P49137	Q9UKV8	1	phosphorylation	up-regulates	0.436	Mk2 was found to phopsphorylate in vitro the ago2 protein in ser387, which was identified as the major ago2 phosphorylation site in cells.and mutation of ser387 to alanineimpairsago2 localization to therna-containing granules termedprocessing bodies	SIGNOR-166615
P06493	Q5BJF6	1	phosphorylation	up-regulates activity	0.543	Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles.	SIGNOR-273584
O60674	P42224	1	phosphorylation	up-regulates	0.806	Phosphorylation at tyr701 by the janus family of tyrosine kinases (jak) leads to stat1 dimerization via its src homology 2 domains, exposure of a dimer-specific nuclear localization signal, and subsequent nuclear translocation.	SIGNOR-235709
P31271	Q15375	1	transcriptional regulation	up-regulates quantity by expression	0.291	Analysis of normalized luciferase expression confirmed that wt HOXA13 regulates gene expression through the EphA7 cis-regulatory DNA element	SIGNOR-261631
P30307	P53779	0	phosphorylation	down-regulates	0.245	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164085
Q9Y5W3	P78509	1	transcriptional regulation	up-regulates quantity by expression	0.2	KLF2 transactivates the reelin promoter in K562 cells.	SIGNOR-266048
Q9Y4K3	O00635	0	polyubiquitination	down-regulates quantity by destabilization	0.43	As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6.	SIGNOR-272009
P60891	P06493	0	phosphorylation	up-regulates activity	0.254	CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103\|In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation	SIGNOR-265728
Q86VW2	P60953	1	guanine nucleotide exchange factor	up-regulates	0.669	Exogenous expression of geft promotes myogenesis of c2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process.	SIGNOR-235391
P00748	P03951	1	cleavage	up-regulates activity	0.494	Activation of factor XI in plasma is dependent on factor XII \| Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.	SIGNOR-263519
P25025	P37231	0	transcriptional regulation	up-regulates quantity by expression	0.264	EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE).	SIGNOR-271682
P48167	P12931	0	phosphorylation	up-regulates	0.27	These findings indicate that glyr function is upregulated by ptks and this modulation is dependent on the tyrosine-413 residue of the beta subunit.	SIGNOR-115705
Q8TCQ1	P01903	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.	SIGNOR-271412
P07949	P17612	0	phosphorylation	down-regulates	0.4	Furthermore, we find that activation of protein kinase a (pka) by forskolin reduces the recruitment of shp2 to ret and negatively affects ligand-mediated neurite outgrowth. In agreement with this, mutation of ser(696), a known pka phosphorylation site in ret, enhances shp2 binding to the receptor and eliminates the effect of forskolin on ligand-induced outgrowth.	SIGNOR-167349
P31749	Q9Y2I7	1	phosphorylation	up-regulates	0.491	Here we report that serine318 on the fyve domain-containing ptdins3p 5-kinase (pikfyve) is a novel substrate for pkb, and show that phosphorylation stimulates the ptdins3p 5-kinase activity of the enzyme.	SIGNOR-252474
Q04864	Q14164	0	phosphorylation	up-regulates	0.354	The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.	SIGNOR-148620
Q96SD1	Q13315	0	phosphorylation	up-regulates	0.619	The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo	SIGNOR-148315
P05305	Q14119	0	transcriptional regulation	up-regulates quantity by expression	0.276	Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone	SIGNOR-266884
P37231	P00533	0	phosphorylation	down-regulates quantity by destabilization	0.513	Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.	SIGNOR-277190
Q8IVM8	P20823	0	transcriptional regulation	up-regulates quantity by expression	0.2	Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells.	SIGNOR-268982
O43521	P28482	0	phosphorylation	down-regulates quantity by destabilization	0.716	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-129874
Q05513	Q8TEW0	1	phosphorylation	up-regulates	0.711	These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity	SIGNOR-94523
P60484	Q8IZP0	1	dephosphorylation	down-regulates quantity by destabilization	0.241	After dephosphorylation by PTEN, Abi1 is degraded by calpains.\|We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway.	SIGNOR-276948
P63000	Q12979	0	gtpase-activating protein	down-regulates activity	0.504	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-260525
P35372	P01213	0	chemical activation	up-regulates activity	0.674	Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.	SIGNOR-258414
P24385	P35222	0	transcriptional regulation	up-regulates quantity by expression	0.801	One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.	SIGNOR-277738
O75116	O14974	1	phosphorylation	down-regulates activity	0.785	Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited.	SIGNOR-249164
P25098	P37840	1	phosphorylation	down-regulates activity	0.2	We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.	SIGNOR-78333
P11309	P53350	1	phosphorylation	down-regulates activity	0.294	This data strongly indicates that Pim1 phosphorylates PLK1 at threonine 210, a site previously reported to be phosphorylated by aurora A kinase during mitosis.	SIGNOR-279749
Q9HB90	Q8NFG4	0	gtpase-activating protein	up-regulates activity	0.695	The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur	SIGNOR-256503
O43602	P45983	0	phosphorylation	up-regulates activity	0.286	DCX phosphorylation by JNK1 is required for glioma suppression.	SIGNOR-279217
P31751	Q9UBK2	1	phosphorylation	down-regulates	0.348	Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.	SIGNOR-155536
P43378	P06213	1	dephosphorylation	down-regulates	0.26	Ectopic expression of ptp-meg2 in cells inhibited insulin-induced phosphorylation of the insulin receptor, while rnai-mediated reduction of ptp-meg2 transcript levels enhanced insulin action	SIGNOR-146676
P54619	P78527	0	phosphorylation	up-regulates activity	0.2	PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity.	SIGNOR-277503
Q7Z6Z7	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.495	HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ].	SIGNOR-278547
Q05655	Q00535	1	phosphorylation	down-regulates activity	0.2	This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.	SIGNOR-277386
P14618	P36956	0	transcriptional regulation	up-regulates quantity by expression	0.29	Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk)	SIGNOR-166381
P62979	P15374	0	cleavage	up-regulates quantity	0.802	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270828
P33527	P68400	0	phosphorylation	up-regulates	0.374	Casein kinase 2_ regulates multidrug resistance-associated protein 1 function via phosphorylation of thr249. This study supports a model in which ck2_ potentiates mrp1 function via direct phosphorylation of thr249.	SIGNOR-197844
P00797	P19544	0	transcriptional regulation	down-regulates quantity by repression	0.421	Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription	SIGNOR-252296
P29474	P31751	0	phosphorylation	up-regulates activity	0.504	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251624
P40763	Q9Y4K3	0	ubiquitination	down-regulates activity	0.47	TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.\|TRAF6 Represses the Transcriptional Activity of STAT3.	SIGNOR-278618
O43781	P18848	0	transcriptional regulation	down-regulates quantity by repression	0.2	Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop.	SIGNOR-275453
O14757	P04637	1	phosphorylation	up-regulates activity	0.78	Phosphorylation by chk1 of at least three of these sites, Ser366, Ser378, and Thr387, was induced by DNA damage.	SIGNOR-217861
Q14247	Q05397	0	phosphorylation	down-regulates activity	0.745	FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.\|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).	SIGNOR-278283
O43524	Q96EB6	0	deacetylation	up-regulates activity	0.911	Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress	SIGNOR-122405
P53350	Q3KR16	1	phosphorylation	up-regulates	0.415	We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.	SIGNOR-179954
P00533	O15492	1	phosphorylation	up-regulates	0.415	Phosphorylation on tyr(168) was mediated by the epidermal growth factor receptor (egfr). We show here that endogenous rgs16 is phosphorylated after epidermal growth factor stimulation of mcf-7 cells.	SIGNOR-98267
P53350	Q15022	1	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
Q05209	P42768	1	dephosphorylation	down-regulates	0.444	Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction.	SIGNOR-121136
Q9NYY3	P37840	1	phosphorylation	down-regulates activity	0.478	Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. Pathological serine 129 phosphorylation regulates membrane accumulation of mutant alpha-synuclein.	SIGNOR-182155
O43318	P61006	1	phosphorylation	up-regulates activity	0.252	In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. \|Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.\|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease	SIGNOR-260266
P17612	O95644	1	phosphorylation	down-regulates	0.385	Here we show that overexpression of pka causes phosphorylation and cytoplasmic accumulation of nf-atc1 in direct opposition to calcineurin by phosphorylating ser-245, ser-269, and ser-294 in the conserved serine-proline repeat domainwe further show that a complete block of nf-atc1 nuclear localization by pka requires a second kinase activity that can be supplied by glycogen synthase kinase-3 (gsk-3)	SIGNOR-93531
Q96A26	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.282	In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region.	SIGNOR-260292
P00533	P03372	1	phosphorylation	up-regulates	0.59	Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er	SIGNOR-115734
P34925	Q86YT6	0	ubiquitination	down-regulates	0.327	We discovered that ryk both physically and functionally interacts with the e3 ubiquitin ligase mind bomb 1 (mib1).We Found that overexpressed ryk and mib1 colocalized and that the overexpression of mib1 leads to the loss of surface ryk expression. In addition, biochemical studies revealed that mib1 promotes the ubiquitination and degradation of ryk. Endogenous ryk and mib1 were required for the wnt-dependent activation of wnt/ctnnb1 signaling	SIGNOR-176282
Q08050	Q9H2X6	0	phosphorylation	up-regulates activity	0.2	In conclusion, the phosphorylation of FOXM1 by HIPK2 can promote FOXM1 transcription activity and cell proliferation in RCC, thus, indicating a potential mechanism for the treatment of human RCC in the future.	SIGNOR-278944
Q9UKX2	Q02078	0	transcriptional regulation	up-regulates quantity by expression	0.325	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238703
P32119	P06239	0	phosphorylation	down-regulates activity	0.2	Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.	SIGNOR-276279
P63000	Q8N103	0	gtpase-activating protein	down-regulates activity	0.402	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-260524
Q9NZV8	Q6PIL6	0	relocalization	up-regulates activity	0.773	KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface	SIGNOR-269004
Q9ULA0	Q9P286	0	phosphorylation	down-regulates quantity by destabilization	0.2	We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. \| PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway.	SIGNOR-275651
P53350	Q15013	1	phosphorylation	down-regulates activity	0.41	Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.	SIGNOR-265970
P53350	Q96CV9	1	phosphorylation	up-regulates	0.539	Here we show that at mitotic entry, plk1 phosphorylates optineurin (optn) at serine 177 and that this dissociates optn from the golgi-localized gtpase rab8, inducing its translocation into the nucleus.	SIGNOR-196367

Q9UQM7

Q9Y4D2

1

phosphorylation

down-regulates activity

0.2

Activated CaMKII interacted with the C-terminal domain of DGLalpha, phosphorylated two serine residues and inhibited DGLalpha activity. |CaMKIIalpha phosphorylates DGLalpha at Ser808 and Ser782

SIGNOR-275540

Q9NS23

Q96GD4

0

phosphorylation

down-regulates

0.438

Here, we show that aurora a and b associate with and phosphorylate rassf1a on serine 203 aurora a regulates prometaphase progression by inhibiting the ability of rassf1a to suppress apc-cdc20 activity.

SIGNOR-184561

Q07954

P12931

0

phosphorylation

up-regulates activity

0.394

We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras

SIGNOR-101535

Q99801

Q9Y463

0

phosphorylation

down-regulates quantity by destabilization

0.332

In addition, an in vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover.

SIGNOR-279610

O14965

Q9NS23

1

phosphorylation

down-regulates

0.448

Aurora-a appears to phosphorylate rassf1a at threonine202 and/or serine203 that reside within the known microtubule-binding domain of rassf1a. Substitutions of these residues with glutamic acid at both positions, mimicking constitutive phosphorylation of rassf1a, disrupt rassf1a interactions with microtubules and abolish its ability to induce m-phase cell cycle arrest.

SIGNOR-155815

Q12778

P06493

0

phosphorylation

down-regulates

0.511

Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1.

SIGNOR-178202

Q8IYW5

Q14669

0

ubiquitination

down-regulates activity

0.465

Here, we show that TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage. We find that RNF168 can be saturated by increasing amounts of DSBs. Depletion of TRIP12 and UBR5 allows accumulation of RNF168 to supraphysiological levels, followed by massive spreading of ubiquitin conjugates and hyperaccumulation of ubiquitin-regulated genome caretakers such as 53BP1 and BRCA1.

SIGNOR-266783

P28482

Q86UC2

1

phosphorylation

up-regulates activity

0.2

ERK1/2 phosphorylate RSPH3. the extent of radiolabeled phosphate incorporation into RSPH3 T286A was much less than that into wild-type RSPH3, suggesting that threonine 286 is the major ERK1/2 phosphorylation site in cells. ERK2 also phosphorylates RSPH3 on threonine 243 to a lesser extent. Phosphorylation of the double mutant T243V/T286A RSPH3 was no more than 20% that of wild-type RSPH3 (Fig. 4, C and D). inhibiting ERK1/2 activity appears to negatively regulate the AKAP function of RSPH3.

SIGNOR-262839

Q9HC98

O96017

0

phosphorylation

down-regulates activity

0.229

Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro .

SIGNOR-279404

P60510

Q13085

1

dephosphorylation

up-regulates activity

0.242

PP4 was also found to directly interact with pACC1‑Ser79 in human HepG2 cells. In conclusion, the present study showed that PP4 may be a novel regulator in hepatic lipogenesis through dephosphorylating ACC1 on serine 79, suggesting that PP4 may be a promising therapeutic target in lipid metabolism disorders.

SIGNOR-267724

Q86YT6

Q9UPN4

1

ubiquitination

down-regulates

0.43

We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined.

SIGNOR-272876

P18031

Q9NZJ5

1

dephosphorylation

down-regulates activity

0.267

Finally, we demonstrated that wild-type PTP1B directly dephosphorylated myc-tagged PERK that had been isolated from tunicamycin-treated HEK293T cells by immunoprecipitation ( xref ).|The ability of PTP1B to dephosphorylate Tyr619 and inactivate PERK is fine tuned by the production of H 2 S by CSE in response to ER stress.

SIGNOR-277051

Q96T68

P68431

1

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263896

O75030

P49840

0

phosphorylation

up-regulates

0.294

Glycogen synthase kinase 3 (gsk3) was found to phosphorylate ser298 in vitro, thereby enhancing the binding of mitf to the tyrosinase promoter

SIGNOR-72878

P53779

O43521

1

phosphorylation

up-regulates activity

0.689

JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity.

SIGNOR-250130

P19883

Q13469

0

transcriptional regulation

up-regulates quantity by expression

0.2

MyoD, CREB, and NFAT Mediate the Transcriptional Activation of the Follistatin Promoter Induced by TSA

SIGNOR-251729

P63000

P31749

0

phosphorylation

down-regulates activity

0.725

Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1

SIGNOR-252576

Q13043

P31751

0

phosphorylation

down-regulates

0.262

Full activation of mst1 requires an activation cleavage that is prevented by the phosphorylation of thr-387 by akt.

SIGNOR-201125

P43004

Q6VVB1

0

ubiquitination

up-regulates activity

0.2

On the contrary, overexpression of the laforin/malin complex promotes the retention of GLT-1 at the plasma membrane.|This is due to a direct ubiquitination of GLT-1 by laforin and malin and/or to changes in the dynamics of its Nedd4.2-mediated endocytosis, which is assisted by specific adaptors (\u03b1- and \u03b2-arrestins).

SIGNOR-278586

Q16236

Q14145

0

ubiquitination

down-regulates quantity

0.813

Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation

SIGNOR-259335

Q92688

P68400

0

phosphorylation

up-regulates

0.234

Here, we are able to report that casein kinase 2 (ck2) phosphorylates april on residue threonine244 (thr(244)) and demonstrate that the ck2-specific inhibitor 4,5,6,7-tetrabromo-2-azabenzimidazole abolishes cd83 expression in activated jurkat t cells by interfering with the nucleocytoplasmic translocation of cd83 mrna

SIGNOR-183158

Q86YJ5

Q8NHL6

1

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271534

P27361

Q14005

1

phosphorylation

up-regulates

0.266

The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 in antigen receptor-, sdf1alpha- and il-2-activated t cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.

SIGNOR-121856

P35222

Q13554

0

phosphorylation

down-regulates

0.289

Camkii represses transcriptionally active _-catenin to mediate acute ethanol neurodegeneration and can phosphorylate _-catenincamkii can directly phosphorylate _-catenin. Using targeted mutagenesis we identified camkii phosphorylation sites within human _-catenin at t332, t472, and s552.

SIGNOR-202833

Q12888

Q99986

0

phosphorylation

up-regulates

0.399

The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size

SIGNOR-197625

P30405

P31751

0

phosphorylation

up-regulates activity

0.2

In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy.

SIGNOR-276875

Q9UBF6

P42574

1

ubiquitination

down-regulates activity

0.2

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271448

P11473

O60315

0

transcriptional regulation

up-regulates quantity by expression

0.2

ZEB, a Krüppel-type transcription factor known to repress the transcription of several genes, binds to two sites within the VDR promoter and activates the transcription of this receptor in a cell-specific manner. Transfection of ZEB into SW620 colon carcinoma cells results in an up-regulation of the expression of endogenous VDR, confirming the role of ZEB in the transcriptional activation of the VDR gene.

SIGNOR-268954

Q9UQL6

Q9Y463

0

phosphorylation

down-regulates activity

0.372

Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279

SIGNOR-235809

Q14289

Q05397

1

phosphorylation

up-regulates

0.524

Activated rock phosphorylates fak on ser732, which is essential for phosphorylation of tyr407 and for cell migration. We further show that pyk2 is activated by vegf-induced clustering of integrin v 3 and is responsible for the phosphorylation of tyr407.

SIGNOR-147070

P50281

Q99558

0

phosphorylation

up-regulates activity

0.2

A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.

SIGNOR-279631

P30304

Q00534

1

dephosphorylation

up-regulates activity

0.704

Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs.

SIGNOR-267569

P10415

P62714

0

dephosphorylation

up-regulates activity

0.385

The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.

SIGNOR-248589

P06493

Q9UNZ2

1

phosphorylation

down-regulates activity

0.325

Now, we have found that p47, which mainly localizes to the nucleus during interphase, is phosphorylated on serine-140 by cdc2 at mitosis. The phosphorylated p47 does not bind to golgi membranes.

SIGNOR-102350

P31749

P04792

1

phosphorylation

down-regulates

0.66

First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.

SIGNOR-252526

P30874

P31629

0

transcriptional regulation

up-regulates quantity by expression

0.411

Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain.

SIGNOR-261617

P49137

Q9UKV8

1

phosphorylation

up-regulates

0.436

Mk2 was found to phopsphorylate in vitro the ago2 protein in ser387, which was identified as the major ago2 phosphorylation site in cells.and mutation of ser387 to alanineimpairsago2 localization to therna-containing granules termedprocessing bodies

SIGNOR-166615

P06493

Q5BJF6

1

phosphorylation

up-regulates activity

0.543

Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles.

SIGNOR-273584

O60674

P42224

1

phosphorylation

up-regulates

0.806

Phosphorylation at tyr701 by the janus family of tyrosine kinases (jak) leads to stat1 dimerization via its src homology 2 domains, exposure of a dimer-specific nuclear localization signal, and subsequent nuclear translocation.

SIGNOR-235709

P31271

Q15375

1

transcriptional regulation

up-regulates quantity by expression

0.291

Analysis of normalized luciferase expression confirmed that wt HOXA13 regulates gene expression through the EphA7 cis-regulatory DNA element

SIGNOR-261631

P30307

P53779

0

phosphorylation

down-regulates

0.245

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164085

Q9Y5W3

P78509

1

transcriptional regulation

up-regulates quantity by expression

0.2

KLF2 transactivates the reelin promoter in K562 cells.

SIGNOR-266048

Q9Y4K3

O00635

0

polyubiquitination

down-regulates quantity by destabilization

0.43

As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6.

SIGNOR-272009

P60891

P06493

0

phosphorylation

up-regulates activity

0.254

CDK1 contributes to upregulation of PRPS1 activity by phosphorylating PRPS1 at S103|In conclusion, compared with upregulation of PRPS1 expression levels, increased PRPS1 activity, which is marked by S103 phosphorylation

SIGNOR-265728

Q86VW2

P60953

1

guanine nucleotide exchange factor

up-regulates

0.669

Exogenous expression of geft promotes myogenesis of c2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process.

SIGNOR-235391

P00748

P03951

1

cleavage

up-regulates activity

0.494

Activation of factor XI in plasma is dependent on factor XII | Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.

SIGNOR-263519

P25025

P37231

0

transcriptional regulation

up-regulates quantity by expression

0.264

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

SIGNOR-271682

P48167

P12931

0

phosphorylation

up-regulates

0.27

These findings indicate that glyr function is upregulated by ptks and this modulation is dependent on the tyrosine-413 residue of the beta subunit.

SIGNOR-115705

Q8TCQ1

P01903

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination.

SIGNOR-271412

P07949

P17612

0

phosphorylation

down-regulates

0.4

Furthermore, we find that activation of protein kinase a (pka) by forskolin reduces the recruitment of shp2 to ret and negatively affects ligand-mediated neurite outgrowth. In agreement with this, mutation of ser(696), a known pka phosphorylation site in ret, enhances shp2 binding to the receptor and eliminates the effect of forskolin on ligand-induced outgrowth.

SIGNOR-167349

P31749

Q9Y2I7

1

phosphorylation

up-regulates

0.491

Here we report that serine318 on the fyve domain-containing ptdins3p 5-kinase (pikfyve) is a novel substrate for pkb, and show that phosphorylation stimulates the ptdins3p 5-kinase activity of the enzyme.

SIGNOR-252474

Q04864

Q14164

0

phosphorylation

up-regulates

0.354

The present results demonstrate that ikkepsilon- and tbk1-mediated phosphorylation of crel in the c-terminal td leads to cytoplasmic dissociation of a crel-ikb_ complex and nuclear accumulation of crel.

SIGNOR-148620

Q96SD1

Q13315

0

phosphorylation

up-regulates

0.619

The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo

SIGNOR-148315

P05305

Q14119

0

transcriptional regulation

up-regulates quantity by expression

0.276

Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone

SIGNOR-266884

P37231

P00533

0

phosphorylation

down-regulates quantity by destabilization

0.513

Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.

SIGNOR-277190

Q8IVM8

P20823

0

transcriptional regulation

up-regulates quantity by expression

0.2

Luciferase reporter gene constructs containing the OAT5 (SLC22A10) and OAT7 (SLC22A9) promoter regions were transactivated by HNF-1 in HepG2 cells.

SIGNOR-268982

O43521

P28482

0

phosphorylation

down-regulates quantity by destabilization

0.716

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-129874

Q05513

Q8TEW0

1

phosphorylation

up-regulates

0.711

These results imply that serine 827 in the apkc binding site of par-3 is a target of apkc and that the regulated interaction between a protein kinase, apkc, and its substrate, par-3, plays an essential role in the establishment of cell polarity

SIGNOR-94523

P60484

Q8IZP0

1

dephosphorylation

down-regulates quantity by destabilization

0.241

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

SIGNOR-276948

P63000

Q12979

0

gtpase-activating protein

down-regulates activity

0.504

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-260525

P35372

P01213

0

chemical activation

up-regulates activity

0.674

Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors.

SIGNOR-258414

P24385

P35222

0

transcriptional regulation

up-regulates quantity by expression

0.801

One of the most well studied activators of CCND1 transcription is β-catenin, which could be actived by AKT signalling to inducing G1/S transition. When β-catenin is translocated from the cytoplasm to the nucleus, it forms a complex with the ternary complex factor (TCF) and/or lymphoid enhancer-binding factor (LEF) and stimulates cyclin D1 gene transcription (Fig. 4C).In agreement with the data described above, a chromatin immunoprecipitation (ChIP) assay confirmed that TNC regulates the binding of β-catenin to the TCF/LEF-binding site in the CCND1 promoter (Fig. 4C). Additionally, the β-cateninbinding activity with respect to the CCND1 promoter was much higher in TNC-overexpression PANC-1 cells than in the vector controls.

SIGNOR-277738

O75116

O14974

1

phosphorylation

down-regulates activity

0.785

Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited.

SIGNOR-249164

P25098

P37840

1

phosphorylation

down-regulates activity

0.2

We found that grk-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and pld2. These findings suggest that gpcrs may be able to indirectly stimulate pld2 activity via their ability to regulate grk-promoted phosphorylation of synuclein.

SIGNOR-78333

P11309

P53350

1

phosphorylation

down-regulates activity

0.294

This data strongly indicates that Pim1 phosphorylates PLK1 at threonine 210, a site previously reported to be phosphorylated by aurora A kinase during mitosis.

SIGNOR-279749

Q9HB90

Q8NFG4

0

gtpase-activating protein

up-regulates activity

0.695

The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur

SIGNOR-256503

O43602

P45983

0

phosphorylation

up-regulates activity

0.286

DCX phosphorylation by JNK1 is required for glioma suppression.

SIGNOR-279217

P31751

Q9UBK2

1

phosphorylation

down-regulates

0.348

Here we describe a mechanism by which insulin, through the intermediary protein kinase akt2/protein kinase b (pkb)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (pgc-1alpha), a global regulator of hepatic metabolism during fasting / phosphorylation of pgc-1? At ser?570 Is required for akt to inhibit recruitment of pgc-1? To chromatin.

SIGNOR-155536

P43378

P06213

1

dephosphorylation

down-regulates

0.26

Ectopic expression of ptp-meg2 in cells inhibited insulin-induced phosphorylation of the insulin receptor, while rnai-mediated reduction of ptp-meg2 transcript levels enhanced insulin action

SIGNOR-146676

P54619

P78527

0

phosphorylation

up-regulates activity

0.2

PRKDC interacted with the AMPK complex and phosphorylated its nucleotide-sensing γ1 subunit PRKAG1/AMPKγ1 at Ser192 and Thr284, both events being significantly reduced upon the activation of the AMPK complex. Alanine substitutions of PRKDC phosphorylation sites in PRKAG1 reduced AMPK complex activation without affecting its nucleotide sensing capacity.

SIGNOR-277503

Q7Z6Z7

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.495

HUWE1 directly binds and ubiquitinates p53 to target it for proteasomal degradation, independently of MDM2 [ xref ].

SIGNOR-278547

Q05655

Q00535

1

phosphorylation

down-regulates activity

0.2

This generates a binding site for the C2 domain of PKCδ, which in turn phosphorylates CDK5 on T77. The resulting dissociation of the CDK5R1/CDK5 complex abolishes the activity of CDK5.

SIGNOR-277386

P14618

P36956

0

transcriptional regulation

up-regulates quantity by expression

0.29

Well-described targets of srebp-1 and the carbohydrate response element binding protein (chrebp), which include the following: fatty acid synthase (fas), acetyl coa carboxylase (acc1), and liver pyruvate kinase (l-pk)

SIGNOR-166381

P62979

P15374

0

cleavage

up-regulates quantity

0.802

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270828

P33527

P68400

0

phosphorylation

up-regulates

0.374

Casein kinase 2_ regulates multidrug resistance-associated protein 1 function via phosphorylation of thr249. This study supports a model in which ck2_ potentiates mrp1 function via direct phosphorylation of thr249.

SIGNOR-197844

P00797

P19544

0

transcriptional regulation

down-regulates quantity by repression

0.421

Here, we show that a splice variant of the Wilms' tumor protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription

SIGNOR-252296

P29474

P31751

0

phosphorylation

up-regulates activity

0.504

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

SIGNOR-251624

P40763

Q9Y4K3

0

ubiquitination

down-regulates activity

0.47

TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.|TRAF6 Represses the Transcriptional Activity of STAT3.

SIGNOR-278618

O43781

P18848

0

transcriptional regulation

down-regulates quantity by repression

0.2

Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop.

SIGNOR-275453

O14757

P04637

1

phosphorylation

up-regulates activity

0.78

Phosphorylation by chk1 of at least three of these sites, Ser366, Ser378, and Thr387, was induced by DNA damage.

SIGNOR-217861

Q14247

Q05397

0

phosphorylation

down-regulates activity

0.745

FAK directly phosphorylates cortactin at Y421 and Y466 and over-expression of cortactin Y421, Y466, and Y482 mutated to phenylalanine (3YF) prevented FAK-enhanced FA turnover and cell motility.|GFP-FAK re-expression in FAK-/- MEFs enhances FA turnover (XREF_FIG) and cortactin knockdown slows FA turnover (XREF_FIG).

SIGNOR-278283

O43524

Q96EB6

0

deacetylation

up-regulates activity

0.911

Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress

SIGNOR-122405

P53350

Q3KR16

1

phosphorylation

up-regulates

0.415

We reported previously that a guanine nucleotide exchange factor, myogef, localizes to the central spindle, activates rhoa, and is required for cytokinesis. In this study, we have found that plk1 (polo-like kinase 1) can phosphorylate myogef, thereby recruiting myogef to the central spindle as well as enhancing myogef activity toward rhoa. The in vitro kinase assay shows that plk1 can phosphorylate myogef on threonine 574.

SIGNOR-179954

P00533

O15492

1

phosphorylation

up-regulates

0.415

Phosphorylation on tyr(168) was mediated by the epidermal growth factor receptor (egfr). We show here that endogenous rgs16 is phosphorylated after epidermal growth factor stimulation of mcf-7 cells.

SIGNOR-98267

P53350

Q15022

1

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

Q05209

P42768

1

dephosphorylation

down-regulates

0.444

Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction.

SIGNOR-121136

Q9NYY3

P37840

1

phosphorylation

down-regulates activity

0.478

Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. Pathological serine 129 phosphorylation regulates membrane accumulation of mutant alpha-synuclein.

SIGNOR-182155

O43318

P61006

1

phosphorylation

up-regulates activity

0.252

In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2 in vitro. |Overall our data suggests that the phosphorylation of Rab8A at Ser111 may influence Switch II-binding by regulators, thus disrupting interactions with its cognate GEF and moderately impairs its interaction with GAPs.|The antagonistic interplay between Ser111 phosphorylation and Thr72 phosphorylation is genetically concordant with how respective mutations in PINK1 and LRRK2 cause Parkinson’s disease

SIGNOR-260266

P17612

O95644

1

phosphorylation

down-regulates

0.385

Here we show that overexpression of pka causes phosphorylation and cytoplasmic accumulation of nf-atc1 in direct opposition to calcineurin by phosphorylating ser-245, ser-269, and ser-294 in the conserved serine-proline repeat domainwe further show that a complete block of nf-atc1 nuclear localization by pka requires a second kinase activity that can be supplied by glycogen synthase kinase-3 (gsk-3)

SIGNOR-93531

Q96A26

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.282

In this work, we report the identification of an HIF-1 alpha-responsive proapoptotic molecule, HGTD-P. Its expression was directly regulated by HIF-1 alpha through a hypoxia-responsive element on the HGTD-P promoter region.

SIGNOR-260292

P00533

P03372

1

phosphorylation

up-regulates

0.59

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

SIGNOR-115734

P34925

Q86YT6

0

ubiquitination

down-regulates

0.327

We discovered that ryk both physically and functionally interacts with the e3 ubiquitin ligase mind bomb 1 (mib1).We Found that overexpressed ryk and mib1 colocalized and that the overexpression of mib1 leads to the loss of surface ryk expression. In addition, biochemical studies revealed that mib1 promotes the ubiquitination and degradation of ryk. Endogenous ryk and mib1 were required for the wnt-dependent activation of wnt/ctnnb1 signaling

SIGNOR-176282

Q08050

Q9H2X6

0

phosphorylation

up-regulates activity

0.2

In conclusion, the phosphorylation of FOXM1 by HIPK2 can promote FOXM1 transcription activity and cell proliferation in RCC, thus, indicating a potential mechanism for the treatment of human RCC in the future.

SIGNOR-278944

Q9UKX2

Q02078

0

transcriptional regulation

up-regulates quantity by expression

0.325

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

SIGNOR-238703

P32119

P06239

0

phosphorylation

down-regulates activity

0.2

Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylated PrxI and PrxII. Phosphorylation of the wild-type protein was detected, whereas that of the Y194F mutant was not (Figure 1B), indicating that Tyr194 is the only site of tyrosine phosphorylation.

SIGNOR-276279

P63000

Q8N103

0

gtpase-activating protein

down-regulates activity

0.402

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-260524

Q9NZV8

Q6PIL6

0

relocalization

up-regulates activity

0.773

KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface

SIGNOR-269004

Q9ULA0

Q9P286

0

phosphorylation

down-regulates quantity by destabilization

0.2

We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. | PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway.

SIGNOR-275651

P53350

Q15013

1

phosphorylation

down-regulates activity

0.41

Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.

SIGNOR-265970

P53350

Q96CV9

1

phosphorylation

up-regulates

0.539

Here we show that at mitotic entry, plk1 phosphorylates optineurin (optn) at serine 177 and that this dissociates optn from the golgi-localized gtpase rab8, inducing its translocation into the nucleus.

SIGNOR-196367