GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q14493	P0DPK2	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265419
P07101	P27361	0	phosphorylation	up-regulates	0.482	In this paper we have studied the phosphorylation and activation of alternatively spliced forms of human th by mapkap kinase-1 , mapkap kinase-2, map kinase, and cam kinase-11	SIGNOR-34678
O00429	P42345	0	phosphorylation	up-regulates activity	0.345	Furthermore, we confirmed also in Jurkat cells that the specific silencing of both ERK1/2 and mTOR by siRNA downregulates Drp1 phosphorylation on Ser616	SIGNOR-275430
Q05513	P52565	1	phosphorylation	up-regulates activity	0.246	Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.\|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation.	SIGNOR-280089
Q9H4A3	Q9H4A3	2	phosphorylation	up-regulates	0.2	We demonstrate that wnk1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its t-loop ser382 residue, possibly triggered by a transautophosphorylation reaction.	SIGNOR-160850
P48431	Q9HCK8	0	transcriptional regulation	down-regulates quantity	0.318	Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells	SIGNOR-268921
Q13627	P37840	1	phosphorylation	up-regulates	0.561	In vitro kinase assay of anti-dyrk1a immunocomplexes demonstrated that dyrk1a could phosphorylate alpha-synuclein at ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by dyrk1a, potentially affecting neuronal cell viability.	SIGNOR-149393
O14965	O14965	2	phosphorylation	up-regulates	0.2	The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability	SIGNOR-205106
P52564	Q9Y6R4	0	phosphorylation	up-regulates activity	0.657	When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.	SIGNOR-62372
Q99576	Q12778	1	relocalization	down-regulates activity	0.301	GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.	SIGNOR-256146
P48023	O43638	0	transcriptional regulation	down-regulates quantity by repression	0.2	As we expected, Fkhl18 suppressed, dose-dependently,human and mouseFasLpromoter in bovine vascularsmooth muscle cells	SIGNOR-261612
P05771	O15519	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276146
P06493	Q96FF9	1	phosphorylation	down-regulates activity	0.711	Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.	SIGNOR-276118
P45983	Q13115	0	dephosphorylation	down-regulates	0.714	Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2	SIGNOR-27756
O95835	Q4VCS5	1	phosphorylation	up-regulates quantity by stabilization	0.523	Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130	SIGNOR-275843
P54756	Q14938	0	transcriptional regulation	up-regulates quantity	0.2	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268909
O14641	Q9NZR2	2	binding	down-regulates activity	0.385	In this study, we have shown that LRP1B inhibited the activity of beta-catenin/TCF signaling possibly by interacting with DVL2. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling.	SIGNOR-259090
P54646	Q9H2X6	1	phosphorylation	down-regulates activity	0.2	AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2\|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro	SIGNOR-275485
P45984	P12931	1	phosphorylation	up-regulates activity	0.355	Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).\|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.	SIGNOR-279221
P37023	O95393	2	binding	up-regulates	0.709	Taken together, our results sug- gest that bmp9 and bmp10 are two spe- cific alk1 ligands that may physiologi- cally trigger the effects of alk1 on angiogenesis	SIGNOR-150201
P11498	Q16654	0	phosphorylation	down-regulates activity	0.373	PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.	SIGNOR-278974
P01137	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.296	MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production	SIGNOR-251740
P51003	P06493	0	phosphorylation	up-regulates activity	0.258	Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPalpha, 537, 545 and 558, thereby leading to increased activity.	SIGNOR-268338
Q96QV6	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271761
P10721	P12931	0	phosphorylation	up-regulates activity	0.386	C-src phosphorylates tyr900 in the second part of the kinase domain of c-kit.	SIGNOR-103999
P46020	P15735	2	binding	down-regulates activity	0.852	Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.	SIGNOR-267407
P23528	Q96S53	0	phosphorylation	down-regulates activity	0.503	Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.	SIGNOR-108753
P48729	P49841	2	binding	up-regulates activity	0.579	In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)]	SIGNOR-184696
P14416	P43250	0	phosphorylation	down-regulates activity	0.447	GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.	SIGNOR-279046
Q99986	P15336	1	phosphorylation	up-regulates	0.371	Vrk1 phosphorylates atf2 mainly on thr-73, stabilizing the atf2 protein and increasing its intracellular level.	SIGNOR-124330
O15530	P48736	2	binding	up-regulates	0.632	Recent reports have also shown that the phosphoinositide-dependent protein kinase-1 (pdk-1), which binds with high affinity to the pi 3-kinase lipid product phosphatidylinositol-3,4,5-trisphosphate (ptdins-3,4,5-p), phosphorylates and potently activates two other pi 3-kinase targets, the protein kinases akt/pkb and p70s6k.	SIGNOR-60567
P0DP91	P00519	0	phosphorylation	up-regulates activity	0.271	These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress	SIGNOR-279317
P17252	Q04637	1	phosphorylation	up-regulates activity	0.258	Phospho-proteomic and mutational analyses revealed that eIF4G1 is a substrate for PKCα at Ser1186.	SIGNOR-276327
P35125	P60953	0	relocalization	up-regulates	0.359	In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.	SIGNOR-98935
Q01196	P28482	0	phosphorylation	up-regulates activity	0.2	We have identified four phosphorylation sites on AML1c that are necessary for transcriptional activity of AML1c in K562 and 293T cells (27).4 Mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.	SIGNOR-138973
Q00613	P45983	0	phosphorylation	down-regulates activity	0.497	JNK is activated by heat shock and phosphorylates HSF-1 on serine 363. JNK Phosphorylation of HSF-1 Leads to Reduction in Its Transcriptional Activity	SIGNOR-250119
Q14195	P49841	0	phosphorylation	up-regulates activity	0.475	Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro	SIGNOR-146011
O60341	Q9UKL0	2	binding	up-regulates activity	0.955	CoREST protects LSD1 from proteasomal degradation and also plays an indispensable role in LSD1-mediated demethylation of nucleosomal substrates in vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity.	SIGNOR-264506
P31749	P31749	2	phosphorylation	up-regulates activity	0.2	Autophosphorylation of Akt on Thr-72 and Ser-246 appeared to require prior phosphorylation of Akt on Thr-308 and Ser-473. Compared with wild-type Akt, Akt/T72A/S246A mutant exhibited markedly reduced basal Akt kinase activity and response to cellular stimulation by insulin-like growth factor-1, and also conferred less cellular resistance to doxorubicin-induced apoptosis.	SIGNOR-276055
P35568	Q05513	0	phosphorylation	down-regulates activity	0.723	Extensive studies have provided evidence that phosphorylation of Ser307 in IRS-1 inhibits IR/IRS-1 complex formation and IRS-1 tyrosine phosphorylation after prolonged insulin-stimulation similar to our results.	SIGNOR-236760
P31749	Q92945	1	phosphorylation	down-regulates activity	0.703	Beta-catenin transcript can be stabilized by either wnt or pi3k-akt signaling activation. Akt phosphorylates ksrp at a unique serine residue akt phosphorylates the mrna decay-promoting factor ksrp at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents ksrp interaction with the exoribonucleolytic complex exosome.	SIGNOR-252497
P19622	P55075	1	transcriptional regulation	down-regulates quantity by repression	0.416	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.	SIGNOR-265801
Q9UQD0	Q13554	0	phosphorylation	up-regulates activity	0.272	CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability\|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.	SIGNOR-275788
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
Q9H6Q3	P36888	2	binding	down-regulates activity	0.248	We screened a panel of SH2 domain-containing proteins and identified SLAP2 as a potent interacting partner of FLT3. We demonstrated that interaction occurs when FLT3 is activated, and also, an intact SH2 domain of SLAP2 is required for binding. Expression of SLAP2 blocked FLT3 downstream signaling cascades including AKT, ERK, p38 and STAT5.	SIGNOR-256155
P29350	O94916	1	dephosphorylation	down-regulates activity	0.343	We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity	SIGNOR-248467
Q92922	P51532	2	binding	up-regulates	0.95	The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.	SIGNOR-65441
P48729	Q86UY5	2	binding	up-regulates quantity	0.2	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273748
P17252	O60346	0	dephosphorylation	down-regulates quantity	0.25	In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha	SIGNOR-237043
P46940	O75122	2	binding	up-regulates activity	0.416	IQGAP1 is a novel CLASP2-interacting protein\| nonphosphorylated CLASP2 on microtubules is allowed to associate with IQGAP1 for the coupling of microtubules to actin filaments at the front of migrating cells.	SIGNOR-264828
Q00341	Q06609	2	binding	up-regulates activity	0.2	We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.	SIGNOR-266697
Q9H228	P63096	2	binding	up-regulates activity	0.492	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256676
P05026	Q96D59	0	polyubiquitination	down-regulates quantity by destabilization	0.2	RNF183 promotes the degradation of Na, K-ATPas. We confirmed that RNF183 interacted with both α1 and β1 subunits; however, we found that RNF183 ubiquitinated only the β1 subunit, not the α1 subunit.	SIGNOR-272218
P04637	O15164	0	ubiquitination	down-regulates	0.532	New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation	SIGNOR-188726
Q13573	P46531	2	binding	up-regulates	0.601	Contact with skip is required for biological activity of notchic. A mutation in the fourth ankyrin repeat that abolished notch signal transduction did not affect interaction with cbf1 but abolished interaction with skip.	SIGNOR-75788
P36888	P22681	2	binding	down-regulates activity	0.436	Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.	SIGNOR-255739
P31431	P17252	0	phosphorylation	up-regulates activity	0.732	The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.	SIGNOR-249149
Q9UP38	P04628	2	binding	up-regulates activity	0.701	Here, we report that the Wnt signal is transduced in muscle progenitor cells by at least two Frizzled (Fz) receptors (Fz1 and/or Fz6)	SIGNOR-217827
Q969H0	Q71F56	1	ubiquitination	down-regulates quantity by destabilization	0.359	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-266688
O60341	Q16695	1	demethylation	up-regulates activity	0.2	Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription.	SIGNOR-264508
P54253	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.441	CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation\|Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1	SIGNOR-278666
Q96PU5	P17612	0	phosphorylation	down-regulates	0.2	Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246).	SIGNOR-128429
P28482	Q96Q27	1	phosphorylation	up-regulates activity	0.265	Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. \|Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.	SIGNOR-272240
P11309	P46531	1	phosphorylation	up-regulates activity	0.27	Interestingly, Pim1 phosphorylated Notch1 and Notch3, but not Notch2 ICD (Figure xref ), which was in line with the observed Pearson correlations ( xref ).\|Our data indicate that endogenous Pim1 and Notch1 interact already in the cytoplasm, which supports the notion that Pim1 enhances nuclear localization and activity of Notch1.	SIGNOR-279643
Q96P20	Q13153	0	phosphorylation	up-regulates activity	0.2	Pak1 phosphorylates NLRP3 to promote inflammasome activation.	SIGNOR-277547
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
P50148	Q99500	2	binding	up-regulates activity	0.517	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257388
P17482	P62324	2	binding	up-regulates activity	0.442	The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.	SIGNOR-221019
O00141	Q92597	1	phosphorylation	up-regulates	0.569	Transient expression of active (sgk1-s422d) and inactive (sgk1-k127a) sgk1 mutants confirmed that activating sgk1 stimulates ndrg1-thr(346/356/366) phosphorylation. dexamethasone (0.2 mum) acutely activated sgk1 and the peak of this response (2-3 h) coincided with the induction of g (na), and both responses were pi3k-dependent. While these data suggest that sgk1 might mediate the rise in g (na), transient expression of the inactive sgk1-k127a mutant did not affect the hormonal induction of g (na) but did suppress the activation of sgk1.	SIGNOR-180821
P23769	Q16539	0	phosphorylation	up-regulates	0.269	P38_ increases gata_2 activity at endogenous target genes by inducing gata_2 multi_site phosphorylation.	SIGNOR-205242
P09238	Q14586	0	transcriptional regulation	down-regulates quantity by repression	0.39	Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10	SIGNOR-266211
P62136	P40763	1	dephosphorylation	down-regulates activity	0.329	Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3.\| However, PD98059, an inhibitor of MEK1/2, had no significant effects on avicin-induced dephosphorylation of Stat3 (Ser 727)	SIGNOR-248563
Q9ULB1	Q9NZ94	2	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264142
P60983	P17612	0	phosphorylation	up-regulates activity	0.307	Protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. PKA is capable of phosphorylating threonine 26 and serine 82.	SIGNOR-249983
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
Q99608	Q9Y6B2	2	binding	up-regulates activity	0.375	The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation.	SIGNOR-237614
P50148	Q92633	2	binding	up-regulates activity	0.544	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257091
Q01638	O95760	2	binding	up-regulates activity	0.925	We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.The binding of IL-33 to cells that express ST2 results in the activation of NF-κB and MAP kinases. Administration of purified IL-33 either in vitro or in vivo leads to the production of TH2-associated cytokines.	SIGNOR-277711
P36956	O43462	0	cleavage	up-regulates activity	0.651	In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted	SIGNOR-267499
P06493	P36956	1	phosphorylation	up-regulates	0.287	Cdk1/cyclin b-mediated phosphorylation stabilizes srebp1 during mitosis.	SIGNOR-148354
P32239	P09471	2	binding	up-regulates activity	0.255	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257238
P19784	Q16543	1	phosphorylation	up-regulates activity	0.489	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250982
P46531	P78504	2	binding	up-regulates activity	0.642	We identify functional fragments of human notch-1 (n-1) and jagged-1 (j-1) which interact in a calcium-dependent manner.	SIGNOR-219253
P42356	Q9Y2G0	2	binding	up-regulates quantity	0.509	PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B	SIGNOR-269093
P13232	P16871	2	binding	up-regulates	0.914	This receptor (il-7r) is a heterodimer consisting of the il-7r chain and the common cytokine ? -chain.	SIGNOR-163548
O15350	O00308	0	polyubiquitination	down-regulates quantity by destabilization	0.283	WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.	SIGNOR-272233
O60674	P01106	2	binding	up-regulates quantity by stabilization	0.451	In this study, we show that Jak2 is involved in c-Myc induction by inducing c-MYC mRNA and protecting c-Myc protein from 26S proteasome-dependent degradation. These results indicate that c-Myc is a downstream target of activated Jak2 in Bcr-Abl positive cells.	SIGNOR-255810
P53350	Q99661	1	phosphorylation	up-regulates activity	0.812	Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation.	SIGNOR-276931
P68400	Q92538	1	phosphorylation	down-regulates quantity by destabilization	0.2	We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation.	SIGNOR-277398
P17252	Q01970	1	phosphorylation	down-regulates	0.481	These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.	SIGNOR-58859
Q13164	O00141	1	phosphorylation	up-regulates	0.388	Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.	SIGNOR-105728
P06241	Q15831	1	phosphorylation	down-regulates activity	0.327	Moreover, Fyn kinase directly phosphorylated LKB1 on tyrosine 261 and 365 residues and mutations of these sites resulted in LKB1 export into the cytoplasm and increased AMPK phosphorylation.	SIGNOR-278477
Q6ZMZ0	Q96LR5	2	binding	up-regulates activity	0.506	We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and	SIGNOR-271592
P41161	P17612	0	phosphorylation	up-regulates activity	0.2	We further show that the increase in erm transcriptional activity after pka phosphorylation is closely correlated with a drastic reduction in the dna binding of the transcription factor. These results indicate that the phosphorylation of erm by pka is involved in erm-mediated transcription and suggest that the activation of erm is probably related to conformational changes.	SIGNOR-111239
P31749	P49918	1	phosphorylation	down-regulates	0.447	Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination	SIGNOR-252535
Q9H270	P35241	2	binding	up-regulates activity	0.347	Vps11 was found to interact with radixin. ERM proteins and the HOPS complex are required for the transition from early to late endosomes. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.	SIGNOR-261312
Q13480	P08581	0	phosphorylation	up-regulates activity	0.674	Gab-1 is phosphorylated on the same residues by HGF and EGF receptors. Among 16 peptides only nine were phosphorylated by the EGF and HGF receptors, namely peptides containing the tyrosine residues 285, 307, 373, 407, 448, 473, 590, 628 and 660. we show that in the response to HGF or EGF, Gab1 is phosphorylated in vivo on the same residues. However, a sustained activation of signaling pathways downstream to Gab1 (as a result of its sustained phosphorylation) is achieved only in response to HGF.	SIGNOR-250290
P52954	P84550	2	binding	down-regulates activity	0.558	Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord.	SIGNOR-238004
P53350	Q14980	1	phosphorylation	down-regulates activity	0.534	Phosphorylation of NuMA by Plk1 at 1833/34 residue can impact its cortical localization.\|These data strongly suggest that Plk1 negatively regulate cortical NuMA localization and that this impact of Plk1 on NuMA is presumably independent of LGN, at least in the anaphase cells.	SIGNOR-279345
Q9H8S9	O95835	2	binding	up-regulates	0.941	Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1	SIGNOR-169752

Q14493

P0DPK2

1

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265419

P07101

P27361

0

phosphorylation

up-regulates

0.482

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

SIGNOR-34678

O00429

P42345

0

phosphorylation

up-regulates activity

0.345

Furthermore, we confirmed also in Jurkat cells that the specific silencing of both ERK1/2 and mTOR by siRNA downregulates Drp1 phosphorylation on Ser616

SIGNOR-275430

Q05513

P52565

1

phosphorylation

up-regulates activity

0.246

Hence, it may be reasonable to deduce that N-formyl-methionyl-leucyl-phenylalanine binds its receptors to activate protein kinase C\u03b6 to generate superoxide, which in turn stimulates the motility in an autocrine manner via the protein kinase C\u03b6-RhoGDI-1-RhoGTPase pathway.|In these cells, protein kinase C zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation.

SIGNOR-280089

Q9H4A3

2

phosphorylation

up-regulates

0.2

We demonstrate that wnk1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its t-loop ser382 residue, possibly triggered by a transautophosphorylation reaction.

SIGNOR-160850

P48431

Q9HCK8

0

transcriptional regulation

down-regulates quantity

0.318

Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells

SIGNOR-268921

Q13627

P37840

1

phosphorylation

up-regulates

0.561

In vitro kinase assay of anti-dyrk1a immunocomplexes demonstrated that dyrk1a could phosphorylate alpha-synuclein at ser-87. Furthermore, aggregates formed by phosphorylated alpha-synuclein have a distinct morphology and are more neurotoxic compared with aggregates composed of unmodified wild type alpha-synuclein. These findings suggest alpha-synuclein inclusion formation regulated by dyrk1a, potentially affecting neuronal cell viability.

SIGNOR-149393

O14965

2

phosphorylation

up-regulates

0.2

The upstream pak1 kinase can phosphorylate aurora a at t288, autophosphorylation appears to be the essential mode of activation. Our experiments suggest that phosphorylation of t288 is important for regulation of the aurora2 kinase both for its activity and its stability

SIGNOR-205106

P52564

Q9Y6R4

0

phosphorylation

up-regulates activity

0.657

When truncated mapkkk4 (deltamapkkk4) was overexpressed in hek293 cells, it was constitutively activeco-expressed map kinase kinase (mkk)-1, mkk-4, mkk-3 and mkk-6 were activated in vivo by deltamapkkk4. All of the above mkks purified from escherichia coli were phosphorylated and activated by deltamapkkk4 immunoprecipitates in vitro.

SIGNOR-62372

Q99576

Q12778

1

relocalization

down-regulates activity

0.301

GILZ inhibits FOXO1, FOXO3, and FOXO4 transcriptional activities measured with natural or synthetic FOXO-responsive promoters in HL-60 cells.

SIGNOR-256146

P48023

O43638

0

transcriptional regulation

down-regulates quantity by repression

0.2

As we expected, Fkhl18 suppressed, dose-dependently,human and mouseFasLpromoter in bovine vascularsmooth muscle cells

SIGNOR-261612

P05771

O15519

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276146

P06493

Q96FF9

1

phosphorylation

down-regulates activity

0.711

Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion.

SIGNOR-276118

P45983

Q13115

0

dephosphorylation

down-regulates

0.714

Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2

SIGNOR-27756

O95835

Q4VCS5

1

phosphorylation

up-regulates quantity by stabilization

0.523

Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130

SIGNOR-275843

P54756

Q14938

0

transcriptional regulation

up-regulates quantity

0.2

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

SIGNOR-268909

O14641

Q9NZR2

2

binding

down-regulates activity

0.385

In this study, we have shown that LRP1B inhibited the activity of beta-catenin/TCF signaling possibly by interacting with DVL2. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling.

SIGNOR-259090

P54646

Q9H2X6

1

phosphorylation

down-regulates activity

0.2

AMPKalpha2-mediated inhibition of WIP1 phosphorylation by HIPK2|Site-directed mutagenesis of Thr112 and Ser114 in the N terminus, and Thr1107 in the C terminus markedly reduced HIPK2 phosphorylation by AMPKalpha2 in vitro

SIGNOR-275485

P45984

P12931

1

phosphorylation

up-regulates activity

0.355

Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.

SIGNOR-279221

P37023

O95393

2

binding

up-regulates

0.709

Taken together, our results sug- gest that bmp9 and bmp10 are two spe- cific alk1 ligands that may physiologi- cally trigger the effects of alk1 on angiogenesis

SIGNOR-150201

P11498

Q16654

0

phosphorylation

down-regulates activity

0.373

PDK4 phosphorylates and inhibits the pyruvate dehydrogenase complex (PDC) which catalyzes the conversion of pyruvate to acetyl-CoA in the glucose oxidation pathway.

SIGNOR-278974

P01137

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.296

MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-β mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-β production

SIGNOR-251740

P51003

P06493

0

phosphorylation

up-regulates activity

0.258

Once an oocyte resumes meiosis, activated CDK1 and ERK1/2 cooperatively mediate the phosphorylation of three serine residues of PAPalpha, 537, 545 and 558, thereby leading to increased activity.

SIGNOR-268338

Q96QV6

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271761

P10721

P12931

0

phosphorylation

up-regulates activity

0.386

C-src phosphorylates tyr900 in the second part of the kinase domain of c-kit.

SIGNOR-103999

P46020

P15735

2

binding

down-regulates activity

0.852

Phk is among the most complex of the protein kinases so far elucidated. It has one catalytic (gamma) subunit and three different regulatory (alpha, beta, and delta) subunits, a molecular mass of 1.3 X 106 daltons, and each holoenzyme molecule is presumed to contain four molecules of each subunit. The three regulatory subunits inhibit the phosphotransferase activity of the gamma subunit.

SIGNOR-267407

P23528

Q96S53

0

phosphorylation

down-regulates activity

0.503

Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.

SIGNOR-108753

P48729

P49841

2

binding

up-regulates activity

0.579

In the absence of secreted wnt ligands, cytosolic beta-catenin is phosphorylated at ser45 by the priming kinase casein kinase 1 (ck1). Consequently, glycogen synthase kinase 3 (gsk3), in complex with axin and adenomatous polyposis coli (apc), phosphorylates beta-catenin at thr41, ser37, and ser33 apc cooperates with axin to promote the phosphorylation of b-catenin by gsk3 [which requires priming phosphorylation by casein kinase 1, alpha-isoform (ck1alpha)]

SIGNOR-184696

P14416

P43250

0

phosphorylation

down-regulates activity

0.447

GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.

SIGNOR-279046

Q99986

P15336

1

phosphorylation

up-regulates

0.371

Vrk1 phosphorylates atf2 mainly on thr-73, stabilizing the atf2 protein and increasing its intracellular level.

SIGNOR-124330

O15530

P48736

2

binding

up-regulates

0.632

Recent reports have also shown that the phosphoinositide-dependent protein kinase-1 (pdk-1), which binds with high affinity to the pi 3-kinase lipid product phosphatidylinositol-3,4,5-trisphosphate (ptdins-3,4,5-p), phosphorylates and potently activates two other pi 3-kinase targets, the protein kinases akt/pkb and p70s6k.

SIGNOR-60567

P0DP91

P00519

0

phosphorylation

up-regulates activity

0.271

These data raise the possibility that tyrosine phosphorylation of CSB by c-Abl promotes redistribution of CSB in the nucleus and enrichment of CSB in the nucleolus in response to oxidative stress

SIGNOR-279317

P17252

Q04637

1

phosphorylation

up-regulates activity

0.258

Phospho-proteomic and mutational analyses revealed that eIF4G1 is a substrate for PKCα at Ser1186.

SIGNOR-276327

P35125

P60953

0

relocalization

up-regulates

0.359

In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.

SIGNOR-98935

Q01196

P28482

0

phosphorylation

up-regulates activity

0.2

We have identified four phosphorylation sites on AML1c that are necessary for transcriptional activity of AML1c in K562 and 293T cells (27).4 Mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. The presence of these mutations results in an increase in the amount of ubiquitinated AML1c in the matrix, and increases the half-life of this insoluble AML1c. One possible model to explain these observations is that phosphorylation might be necessary for the normal process of both proteasome degradation and transcriptional activation.

SIGNOR-138973

Q00613

P45983

0

phosphorylation

down-regulates activity

0.497

JNK is activated by heat shock and phosphorylates HSF-1 on serine 363. JNK Phosphorylation of HSF-1 Leads to Reduction in Its Transcriptional Activity

SIGNOR-250119

Q14195

P49841

0

phosphorylation

up-regulates activity

0.475

Together, these results suggest that crmp4 is able to increase neurite formation and elongation in neurons, although not as potently as crmp2, and that this process is regulated by ser522/ser518/thr514/thr509 phosphorylation in both cases. We demonstrate that cdk5 primes crmp2 and crmp4 for subsequent phosphorylation by gsk3, whereas dyrk2, phosphorylates and primes only crmp4 in vitro

SIGNOR-146011

O60341

Q9UKL0

2

binding

up-regulates activity

0.955

CoREST protects LSD1 from proteasomal degradation and also plays an indispensable role in LSD1-mediated demethylation of nucleosomal substrates in vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity.

SIGNOR-264506

P31749

2

phosphorylation

up-regulates activity

0.2

Autophosphorylation of Akt on Thr-72 and Ser-246 appeared to require prior phosphorylation of Akt on Thr-308 and Ser-473. Compared with wild-type Akt, Akt/T72A/S246A mutant exhibited markedly reduced basal Akt kinase activity and response to cellular stimulation by insulin-like growth factor-1, and also conferred less cellular resistance to doxorubicin-induced apoptosis.

SIGNOR-276055

P35568

Q05513

0

phosphorylation

down-regulates activity

0.723

Extensive studies have provided evidence that phosphorylation of Ser307 in IRS-1 inhibits IR/IRS-1 complex formation and IRS-1 tyrosine phosphorylation after prolonged insulin-stimulation similar to our results.

SIGNOR-236760

P31749

Q92945

1

phosphorylation

down-regulates activity

0.703

Beta-catenin transcript can be stabilized by either wnt or pi3k-akt signaling activation. Akt phosphorylates ksrp at a unique serine residue akt phosphorylates the mrna decay-promoting factor ksrp at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents ksrp interaction with the exoribonucleolytic complex exosome.

SIGNOR-252497

P19622

P55075

1

transcriptional regulation

down-regulates quantity by repression

0.416

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression.

SIGNOR-265801

Q9UQD0

Q13554

0

phosphorylation

up-regulates activity

0.272

CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability|mmobilized peptide arrays and nanoflow LC-electrospray ionization/MS of Nav1.6 reveal potential sites of CaMKII phosphorylation, specifically Ser-561 and Ser-641/Thr-642 within the first intracellular loop of the channel.

SIGNOR-275788

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

Q9H6Q3

P36888

2

binding

down-regulates activity

0.248

We screened a panel of SH2 domain-containing proteins and identified SLAP2 as a potent interacting partner of FLT3. We demonstrated that interaction occurs when FLT3 is activated, and also, an intact SH2 domain of SLAP2 is required for binding. Expression of SLAP2 blocked FLT3 downstream signaling cascades including AKT, ERK, p38 and STAT5.

SIGNOR-256155

P29350

O94916

1

dephosphorylation

down-regulates activity

0.343

We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity

SIGNOR-248467

Q92922

P51532

2

binding

up-regulates

0.95

The remodeling activity of brg1 and hbrm is stimulated by baf170/baf155 and is further stimulated when ini1 is added.

SIGNOR-65441

P48729

Q86UY5

2

binding

up-regulates quantity

0.2

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273748

P17252

O60346

0

dephosphorylation

down-regulates quantity

0.25

In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha

SIGNOR-237043

P46940

O75122

2

binding

up-regulates activity

0.416

IQGAP1 is a novel CLASP2-interacting protein| nonphosphorylated CLASP2 on microtubules is allowed to associate with IQGAP1 for the coupling of microtubules to actin filaments at the front of migrating cells.

SIGNOR-264828

Q00341

Q06609

2

binding

up-regulates activity

0.2

We show that vigilin interacts with the DNA damage response (DDR) proteins RAD51 and BRCA1, and vigilin depletion impairs their recruitment to DSB sites.

SIGNOR-266697

Q9H228

P63096

2

binding

up-regulates activity

0.492

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256676

P05026

Q96D59

0

polyubiquitination

down-regulates quantity by destabilization

0.2

RNF183 promotes the degradation of Na, K-ATPas. We confirmed that RNF183 interacted with both α1 and β1 subunits; however, we found that RNF183 ubiquitinated only the β1 subunit, not the α1 subunit.

SIGNOR-272218

P04637

O15164

0

ubiquitination

down-regulates

0.532

New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation

SIGNOR-188726

Q13573

P46531

2

binding

up-regulates

0.601

Contact with skip is required for biological activity of notchic. A mutation in the fourth ankyrin repeat that abolished notch signal transduction did not affect interaction with cbf1 but abolished interaction with skip.

SIGNOR-75788

P36888

P22681

2

binding

down-regulates activity

0.436

Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.

SIGNOR-255739

P31431

P17252

0

phosphorylation

up-regulates activity

0.732

The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant.

SIGNOR-249149

Q9UP38

P04628

2

binding

up-regulates activity

0.701

Here, we report that the Wnt signal is transduced in muscle progenitor cells by at least two Frizzled (Fz) receptors (Fz1 and/or Fz6)

SIGNOR-217827

Q969H0

Q71F56

1

ubiquitination

down-regulates quantity by destabilization

0.359

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-266688

O60341

Q16695

1

demethylation

up-regulates activity

0.2

Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription.

SIGNOR-264508

P54253

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.441

CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation|Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1

SIGNOR-278666

Q96PU5

P17612

0

phosphorylation

down-regulates

0.2

Nedd4-2 was a substrate for phosphorylation by pka in vitro and in cells;three nedd4-2 residues were phosphorylated by pka and were required for camp to inhibit nedd4-2 (relative functional importance ser-327 > ser-221 > thr-246).

SIGNOR-128429

P28482

Q96Q27

1

phosphorylation

up-regulates activity

0.265

Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.

SIGNOR-272240

P11309

P46531

1

phosphorylation

up-regulates activity

0.27

Interestingly, Pim1 phosphorylated Notch1 and Notch3, but not Notch2 ICD (Figure xref ), which was in line with the observed Pearson correlations ( xref ).|Our data indicate that endogenous Pim1 and Notch1 interact already in the cytoplasm, which supports the notion that Pim1 enhances nuclear localization and activity of Notch1.

SIGNOR-279643

Q96P20

Q13153

0

phosphorylation

up-regulates activity

0.2

Pak1 phosphorylates NLRP3 to promote inflammasome activation.

SIGNOR-277547

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

P50148

Q99500

2

binding

up-regulates activity

0.517

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257388

P17482

P62324

2

binding

up-regulates activity

0.442

The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation.

SIGNOR-221019

O00141

Q92597

1

phosphorylation

up-regulates

0.569

Transient expression of active (sgk1-s422d) and inactive (sgk1-k127a) sgk1 mutants confirmed that activating sgk1 stimulates ndrg1-thr(346/356/366) phosphorylation. dexamethasone (0.2 mum) acutely activated sgk1 and the peak of this response (2-3 h) coincided with the induction of g (na), and both responses were pi3k-dependent. While these data suggest that sgk1 might mediate the rise in g (na), transient expression of the inactive sgk1-k127a mutant did not affect the hormonal induction of g (na) but did suppress the activation of sgk1.

SIGNOR-180821

P23769

Q16539

0

phosphorylation

up-regulates

0.269

P38_ increases gata_2 activity at endogenous target genes by inducing gata_2 multi_site phosphorylation.

SIGNOR-205242

P09238

Q14586

0

transcriptional regulation

down-regulates quantity by repression

0.39

Furthermore, ZNF267 binds to the MMP-10 promoter region as demonstrated by chromatin immunoprecipitation assays. In conclusion, our results suggest that ZNF267 as a negative transcriptional regulator of MMP-10

SIGNOR-266211

P62136

P40763

1

dephosphorylation

down-regulates activity

0.329

Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3.| However, PD98059, an inhibitor of MEK1/2, had no significant effects on avicin-induced dephosphorylation of Stat3 (Ser 727)

SIGNOR-248563

Q9ULB1

Q9NZ94

2

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264142

P60983

P17612

0

phosphorylation

up-regulates activity

0.307

Protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. PKA is capable of phosphorylating threonine 26 and serine 82.

SIGNOR-249983

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

Q99608

Q9Y6B2

2

binding

up-regulates activity

0.375

The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation.

SIGNOR-237614

P50148

Q92633

2

binding

up-regulates activity

0.544

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257091

Q01638

O95760

2

binding

up-regulates activity

0.925

We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.The binding of IL-33 to cells that express ST2 results in the activation of NF-κB and MAP kinases. Administration of purified IL-33 either in vitro or in vivo leads to the production of TH2-associated cytokines.

SIGNOR-277711

P36956

O43462

0

cleavage

up-regulates activity

0.651

In order to activate transcription, the NH2-terminal domain of the SREBP must be released from the membrane so that it can enter the nucleus. This release has been studied most extensively for one of the SREBPs, namely, SREBP-2. However, the mechanism appears to be similar for the other SREBPs (SREBP-1a and -1c) (1). Release of the NH2-terminal domain is accomplished by a two-step proteolytic event that is regulated by sterols (3). In sterol-depleted mammalian cells, this proteolysis is initiated by the Site-1 protease (S1P), which cleaves human SREBP-2 between the Leu522-Ser523 bond in the sequence RSVL S (4). This cleavage requires formation of a complex between SREBP and SCAP, a polytopic membrane protein of the ER, and it is prevented when this complex is disrupted

SIGNOR-267499

P06493

P36956

1

phosphorylation

up-regulates

0.287

Cdk1/cyclin b-mediated phosphorylation stabilizes srebp1 during mitosis.

SIGNOR-148354

P32239

P09471

2

binding

up-regulates activity

0.255

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257238

P19784

Q16543

1

phosphorylation

up-regulates activity

0.489

Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. | In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.

SIGNOR-250982

P46531

P78504

2

binding

up-regulates activity

0.642

We identify functional fragments of human notch-1 (n-1) and jagged-1 (j-1) which interact in a calcium-dependent manner.

SIGNOR-219253

P42356

Q9Y2G0

2

binding

up-regulates quantity

0.509

PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B

SIGNOR-269093

P13232

P16871

2

binding

up-regulates

0.914

This receptor (il-7r) is a heterodimer consisting of the il-7r chain and the common cytokine ? -chain.

SIGNOR-163548

O15350

O00308

0

polyubiquitination

down-regulates quantity by destabilization

0.283

WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.

SIGNOR-272233

O60674

P01106

2

binding

up-regulates quantity by stabilization

0.451

In this study, we show that Jak2 is involved in c-Myc induction by inducing c-MYC mRNA and protecting c-Myc protein from 26S proteasome-dependent degradation. These results indicate that c-Myc is a downstream target of activated Jak2 in Bcr-Abl positive cells.

SIGNOR-255810

P53350

Q99661

1

phosphorylation

up-regulates activity

0.812

Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation.

SIGNOR-276931

P68400

Q92538

1

phosphorylation

down-regulates quantity by destabilization

0.2

We show that, in mitosis, GBF1 is phosphorylated on Ser292 and Ser297 by casein kinase-2 allowing recognition by the F-box protein βTrCP. GBF1 interaction with βTrCP recruits GBF1 to the SCFβTrCP ubiquitin ligase complex, triggering its degradation.

SIGNOR-277398

P17252

Q01970

1

phosphorylation

down-regulates

0.481

These data establish that direct phosphorylation by pka of ser1105 in the putative g-box of plcbeta3 inhibits galphaq-stimulated plcbeta3 activity.

SIGNOR-58859

Q13164

O00141

1

phosphorylation

up-regulates

0.388

Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.

SIGNOR-105728

P06241

Q15831

1

phosphorylation

down-regulates activity

0.327

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

SIGNOR-278477

Q6ZMZ0

Q96LR5

2

binding

up-regulates activity

0.506

We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and

SIGNOR-271592

P41161

P17612

0

phosphorylation

up-regulates activity

0.2

We further show that the increase in erm transcriptional activity after pka phosphorylation is closely correlated with a drastic reduction in the dna binding of the transcription factor. These results indicate that the phosphorylation of erm by pka is involved in erm-mediated transcription and suggest that the activation of erm is probably related to conformational changes.

SIGNOR-111239

P31749

P49918

1

phosphorylation

down-regulates

0.447

Cdk inhibitor p57 (kip2) is downregulated by akt during her2-mediated tumorigenicityakt phosphorylates p57 on ser 282 or thr310. Akt activity results in destabilization of p57 by accelerating turnover rate of p57 and enhancing p57 ubiquitination

SIGNOR-252535

Q9H270

P35241

2

binding

up-regulates activity

0.347

Vps11 was found to interact with radixin. ERM proteins and the HOPS complex are required for the transition from early to late endosomes. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.

SIGNOR-261312

Q13480

P08581

0

phosphorylation

up-regulates activity

0.674

Gab-1 is phosphorylated on the same residues by HGF and EGF receptors. Among 16 peptides only nine were phosphorylated by the EGF and HGF receptors, namely peptides containing the tyrosine residues 285, 307, 373, 407, 448, 473, 590, 628 and 660. we show that in the response to HGF or EGF, Gab1 is phosphorylated in vivo on the same residues. However, a sustained activation of signaling pathways downstream to Gab1 (as a result of its sustained phosphorylation) is achieved only in response to HGF.

SIGNOR-250290

P52954

P84550

2

binding

down-regulates activity

0.558

Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord.

SIGNOR-238004

P53350

Q14980

1

phosphorylation

down-regulates activity

0.534

Phosphorylation of NuMA by Plk1 at 1833/34 residue can impact its cortical localization.|These data strongly suggest that Plk1 negatively regulate cortical NuMA localization and that this impact of Plk1 on NuMA is presumably independent of LGN, at least in the anaphase cells.

SIGNOR-279345

Q9H8S9

O95835

2

binding

up-regulates

0.941

Lats1/2 are activated by association with the highly homologous scaffold proteins mps one binder kinase activator-like 1a (mobkl1a) and 1b (mobkl1b), which are collectively referred to as mob1

SIGNOR-169752