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
P08240	P61011	2	binding	up-regulates activity	0.2	The multi-domain SRP GTPase SRP54 recognizes the signal with its M domain and establishes the targeting complex consisting of its NG domain bound to the homologous NG domain of the SRP receptor SRα at a proximal ribosome binding site.	SIGNOR-261163
O95786	P36873	0	dephosphorylation	up-regulates activity	0.2	We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.\|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively	SIGNOR-264580
Q15418	P50549	1	phosphorylation	up-regulates activity	0.35	Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.	SIGNOR-249163
P45983	P30307	1	phosphorylation	down-regulates	0.411	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-164089
Q96RI0	Q03113	2	binding	up-regulates	0.485	Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).	SIGNOR-196012
O43524	O14920	0	phosphorylation	down-regulates	0.692	Ikkbeta phosphorylates foxo3a at ser644. Ikappab kinase (ikk) physically interacts with, phosphorylates, and inhibits foxo3a independent of akt and causes proteolysis of foxo3a via the ub-dependent proteasome pathway	SIGNOR-124207
P63244	Q92615	2	binding	up-regulates activity	0.2	Here we show that LARP4B is a cytoplasmic protein that co-sediments with polysomes and accumulates upon stress induction in stress granules. Biochemical studies further show that the protein interacts with two key factors of the translational machinery, namely, the cytoplasmic poly(A) binding protein (PABPC1) and the receptor for activated C Kinase (RACK1). The biochemical and functional data of LARP4B presented in this study suggest a possible mode of action of LARP4B in translation. Assuming that LARP4B interacts with mRNA-associated PABPC1 and RACK1 simultaneously, it may form a bridge between the 3′ end of mRNAs and the initiating ribosome. This process would lead to mRNA circularization, possibly in an analogous way as it has been described for PABPC1 and eIF4G, the scaffold protein of the cap-binding complex.	SIGNOR-260941
Q9BXW9	P38398	0	ubiquitination	up-regulates activity	0.845	The major genetic evidence supporting ubiquitin ligase function for BRCA1 in vivo comes from studies on the FANCD2 protein. Whereas in wild‐type cells the FANCD2 protein co‐localizes with BRCA1 in nuclear foci and becomes monoubiquitylated in response to DNA damage, HCC1937 cells, which encode a mutated form of BRCA1, are largely defective for both monoubiquitylation of FANCD2 and foci formation	SIGNOR-263236
Q96FA3	Q9NWZ3	0	phosphorylation	up-regulates activity	0.658	The E3 ubiquitin ligase Pellino can be activated by phosphorylation in vitro, catalyzed by IL-1 receptor-associated kinase 1 (IRAK1) or IRAK4. Here, we show that phosphorylation enhances the E3 ligase activity of Pellino 1. Unusually, the full activation of Pellino 1 can be achieved by phosphorylating any one of several different sites (Ser-76, Thr-86, Thr-288, or Ser-293) or a combination of other sites (Ser-78, Thr-80, and Ser-82). Here, we show that Pellino is phosphorylated at multiple sites by IRAK1 and IRAK4 and that activation can be achieved by phosphorylating any one of several sites or a combination of other sites.	SIGNOR-276128
Q13131	P13569	1	phosphorylation	down-regulates activity	0.493	AMPK phosphorylates CFTR¬†in vitro¬†at two essential serines (Ser737and Ser768) in the R domain, formerly identified as "inhibitory" PKA sites.\|Interestingly two of these sites, namely Ser737 and Ser768, have been identified as “inhibitory” R domain sites, i.e. when mutated to alanines they augment the open probability of CFTR relative to wild type\|Our present results suggest that it might be AMPK rather than PKA that is phosphorylating Ser737 and Ser768 under baseline conditions	SIGNOR-259858
P11717	O60664	0	relocalization	up-regulates activity	0.725	TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.	SIGNOR-253092
Q9NPD5	P42229	0	transcriptional regulation	up-regulates quantity by expression	0.2	PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.\|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.	SIGNOR-268990
O15503	Q9UKV5	0	ubiquitination	down-regulates quantity by destabilization	0.525	The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.\|gp78 mediates the degradation of Insig-1 and Insig-2.	SIGNOR-278567
P09601	P69905	1	null	down-regulates activity	0.253	Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme	SIGNOR-251813
P60891	Q13131	0	phosphorylation	down-regulates activity	0.2	We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.	SIGNOR-265729
Q8IZL9	Q9UPZ9	1	phosphorylation	up-regulates	0.2	Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.	SIGNOR-138420
O76075	O00273	2	binding	down-regulates	0.929	Dff is a heterodimer of 40 kda and 45 kda subunits.	SIGNOR-29729
P48729	P01106	1	phosphorylation	down-regulates quantity by destabilization	0.282	Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.	SIGNOR-276387
Q9UKF7	P17252	0	phosphorylation	up-regulates activity	0.319	Only BIM-I caused a reduction in 14-3-3 binding (Figure 3B), suggesting that PKC could be responsible for one or both of the serine phosphorylations, pSer274 and pSer299.	SIGNOR-273801
P32121	P32248	0	relocalization	up-regulates activity	0.377	B-Arrestin-2 is recruited to CCR7 following stimulation with CCL19, but not CCL21.	SIGNOR-278124
Q09472	Q01543	2	binding	up-regulates	0.291	P300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380	SIGNOR-202682
O60315	O00257	0	sumoylation	down-regulates quantity by destabilization	0.331	Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription.	SIGNOR-268955
P18848	P49589	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269416
O00311	O14757	0	phosphorylation	up-regulates	0.734	Chk1 directly phosphorylates essential s-phase kinases cdc7.	SIGNOR-163161
Q5D1E8	P23769	1	post transcriptional regulation	up-regulates quantity	0.2	Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA	SIGNOR-259943
Q13671	P01116	2	binding	up-regulates	0.598	We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1.	SIGNOR-113970
P61764	Q02410	2	binding	up-regulates activity	0.702	Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.	SIGNOR-264035
O76094	Q9UHB9	2	binding	up-regulates activity	0.99	Taken together our data show that binding of the SRP68/72 heterodimer follows an ultrasensitive response dependent on the SRP72 C-terminus. Although the large solenoids of SRP68/72 have not been structurally characterized due to intrinsic flexibility, they serve as important contact sites in ribosome interaction.	SIGNOR-261164
P67775	Q7Z2W7	1	dephosphorylation	down-regulates activity	0.2	Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.	SIGNOR-273793
P17480	Q05195	0	transcriptional regulation	down-regulates quantity by repression	0.36	MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation\|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.	SIGNOR-269646
Q9BX66	P00519	0	phosphorylation	up-regulates activity	0.424	We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.	SIGNOR-278153
P68400	P42768	1	phosphorylation	up-regulates	0.354	Here we identify two phosphorylation sites in the vca domain of wasp at serines 483 and 484. S483 and s484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the vca domain for the arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length wasp molecule.	SIGNOR-101268
Q05655	P98082	1	phosphorylation	down-regulates	0.296	Mutational analysis revealed that a dab2 ser(24) phosphorylation mutant (s24a) abrogated the inhibitory function of dab2.	SIGNOR-127198
Q13501	P19474	0	ubiquitination	down-regulates activity	0.404	TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.\|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.	SIGNOR-278602
Q16877	Q9Y6Q9	1	phosphorylation	up-regulates activity	0.326	PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output	SIGNOR-267269
Q96RG2	P49841	1	phosphorylation	down-regulates activity	0.288	In vitro, PASK directly phosphorylates GSK3\u03b2 on its inactivating phosphorylation site Ser(9).\|We conclude that PASK phosphorylates and inactivates GSK3\u03b2, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3\u03b2-mediated PDX-1 protein degradation in pancreatic \u03b2-cells.	SIGNOR-279639
Q16539	O43524	1	phosphorylation	up-regulates	0.521	Ogether, our results suggest that p38 phosphorylation of foxo3a on ser-7 is essential for its nuclear relocalization in response to doxorubicin	SIGNOR-177927
P46108	Q9Y4K4	2	binding	up-regulates activity	0.364	Two novel candidates for signalling partners of Crk family adapter proteins, the hematopoietic progenitor kinase 1 (HPK1) and the kinase homologous to SPS1/STE20 (KHS), were found to bind with great selectivity to the first SH3 domains of c-Crk and CRKL.\|These results make it likely that HPK1 and KHS participate in the signal transduction of Crk family adapter proteins in certain cell types.	SIGNOR-262830
P51148	Q99698	2	binding	down-regulates activity	0.2	Mauve interacts with Rab5, Msps, and gamma-tubulin\|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment	SIGNOR-266003
P35968	P35968	2	phosphorylation	up-regulates	0.2	Binding of vegf to the receptor induces dimerisation and autophosphorylation of specific intracellular tyrosine residues. Activation of intracellular cascades results in proliferation, migration, survival and increased permeability.	SIGNOR-157093
Q8NG06	O95786	1	ubiquitination	up-regulates activity	0.2	Specifically, the ubiquitin E3 ligase TRIM25 ubiquitinates K172 in the CARD2 of RIG-I, which is essential for the efficient interaction of RIG-I with MAVS and thereby for antiviral signal transduction	SIGNOR-264582
O95835	Q7L9L4	2	binding	up-regulates	0.921	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-169795
O00141	P51608	0	transcriptional regulation	down-regulates quantity by repression	0.292	These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.	SIGNOR-264543
O95352	Q9GZQ8	2	binding	up-regulates	0.873	These results indicated that the fap motif of atg7 is indispensable for formation of the atg3-lc3 e2-substrate intermediate through the interaction of atg7 with atg3.	SIGNOR-195239
O94907	P50553	0	transcriptional regulation	down-regulates quantity by repression	0.306	We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.	SIGNOR-245885
P35568	P45984	0	phosphorylation	down-regulates	0.706	Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632	SIGNOR-118877
Q712K3	P19784	0	phosphorylation	up-regulates activity	0.449	UBC3B is specifically phosphorylated by CK2 in vitro and in vivo. We mapped by deletions and site directed mutagenesis the phosphorylation site to a serine residue within the C-terminal domain in position 233 of UBC3B and in the corresponding serine residue of UBC3. \| Following CK2-dependent phosphorylation both UBC3B and UBC3 bind to the F-box protein beta-TrCP, the substrate recognition subunit of an SCF (Skp1, Cul1, F-box) ubiquitin ligase. Furthermore, we observed that co-transfection of CK2alpha' together with UBC3B, but not with UBC3DeltaC, enhances the degradation of beta-catenin.	SIGNOR-251047
Q13324	P06850	2	binding	up-regulates activity	0.917	The actions of CRH are transduced through CRH receptors, which belong to the class II/secretin-like family of the G-protein coupled receptor (GPCR) superfamily (Martin et al. 2005). There are three types of CRH receptors – type 1 (CRHR1), type 2 (CRHR2) and type 3 (CRHR3). Among these, CRHR3 has not been identified in mammals. \|CRH is a high-affinity ligand of CRHR1. It also binds to CRHR2, but with lower affinity	SIGNOR-268611
P45983	P04637	1	phosphorylation	up-regulates	0.796	Activated jnk phosphorylates p53	SIGNOR-59812
P16220	P35680	2	binding	up-regulates activity	0.373	The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays.	SIGNOR-241323
P04150	P28562	1	null	up-regulates quantity	0.58	Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1\|Both induction of MKP-1 expression and inhibition of its degradation are necessary for glucocorticoid-mediated inhibition of Erk-1/2 activation. In NIH-3T3 fibroblasts, although glucocorticoids up-regulate the MKP-1 level, they do not attenuate the proteasomal degradation of this protein and consequently they are unable to inhibit Erk-1/2 activity.	SIGNOR-253546
Q96Q05	O14920	2	binding	up-regulates activity	0.489	We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK(beta), but not IKK(alpha) or IKK(gamma). NIBP overexpression potentiates tumor necrosis factor-alpha-induced NF-kappaB activation through increased phosphorylation of the IKK complex and its downstream I(kappa)B(alpha) and p65 substrates.	SIGNOR-269673
P54646	P54619	2	binding	up-regulates	0.897	Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.	SIGNOR-139173
Q86X55	P53778	0	phosphorylation	down-regulates activity	0.363	Here, we identify a role for the mitogen-activated protein kinase (MAPK) p38g/MAPK12 as a critical regulator of satellite stem cell fate through phosphorylation of Carm1.	SIGNOR-255897
P06493	P30304	2	phosphorylation	up-regulates	0.842	Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.	SIGNOR-95260
Q15382	Q8IW41	0	phosphorylation	down-regulates activity	0.401	Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation.	SIGNOR-276313
P24941	Q08050	1	phosphorylation	up-regulates activity	0.75	We demonstrated that FoxM1B transcriptional activity requires binding of either S-phase or M-phase Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins.	SIGNOR-250731
P29353	Q13588	2	binding	up-regulates	0.506	T cell activation effects an increase in grap association with p36/38, shc, sos, and dynamin.	SIGNOR-45528
P53350	P41279	0	phosphorylation	up-regulates	0.2	Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210	SIGNOR-92274
Q9UGI0	Q15672	1	deubiquitination	down-regulates activity	0.331	Trabid inhibits Twist1 activity by cleaving RNF8-mediated Twist1 K63-linked ubiquitination	SIGNOR-273502
Q13950	P06493	0	phosphorylation	up-regulates	0.479	In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.	SIGNOR-143586
O15198	O00238	0	phosphorylation	up-regulates activity	0.708	Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.	SIGNOR-255264
Q9UHD2	Q92985	1	phosphorylation	up-regulates activity	0.768	In most cell types, IRF7 is phosphorylated and activated by IKK\u03b5 and TBK1 after viral infection.\|We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKK\u03b5 or TBK1 is inhibited by ORF45.	SIGNOR-278216
Q06830	P00519	0	phosphorylation	down-regulates activity	0.387	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-276278
Q16576	Q13131	0	phosphorylation	up-regulates activity	0.2	AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314\| interaction between RBBP7 and HAT1 is required for acetyltransferase activity	SIGNOR-264784
P31152	Q05923	2	phosphorylation	up-regulates activity	0.353	However, co-expression of ERK4 significantly increased the half-life of DUSP2 (XREF_FIG).\|In support of the latter notion we have shown that wild-type ERK4 can phosphorylate DUSP2 in vitro and future studies will be aimed at identifying the relevant site (s) of modification and determining their influence on DUSP2 stability.	SIGNOR-278959
P27037	P13385	2	binding	down-regulates	0.642	Here we show that cripto can form a complex with activin and actrii/iib cripto inhibited crosslinking of activin to alk4 and the association of alk4 with actrii/iib.	SIGNOR-100052
Q9Y566	Q9P1A6	0	relocalization	up-regulates activity	0.756	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264589
O95747	Q96J92	0	phosphorylation	up-regulates activity	0.48	In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].\|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].	SIGNOR-278389
O94916	P29350	0	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
Q99684	P14921	2	binding	down-regulates activity	0.426	Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.	SIGNOR-254201
Q9Y4X5	O60573	1	ubiquitination	down-regulates quantity by destabilization	0.678	Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation.	SIGNOR-268848
P10915	P08254	0	cleavage	down-regulates quantity by destabilization	0.384	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256330
P26447	O94916	0	transcriptional regulation	up-regulates quantity by expression	0.478	As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009).	SIGNOR-274115
P10721	P29350	2	binding	down-regulates	0.576	Shp-1 binds and negatively modulates the c-kit receptor by interaction with tyrosine 569 in the c-kit juxtamembrane domain.	SIGNOR-56104
P19086	Q99677	2	binding	up-regulates activity	0.2	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-257325
P19174	P16520	2	binding	up-regulates	0.2	Furthermore, this work suggested that the g subunits released upon gi activation activated phospholipase c (plc- ) to produce inositol 3-phosphate (ip3), which would subsequently increase intracellular ca2+ abundance.	SIGNOR-199135
Q13224	P17612	0	phosphorylation	up-regulates activity	0.414	Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca(2+) permeation and Ca(2+) signaling in spines.	SIGNOR-276616
P28482	Q8WZ42	1	phosphorylation	up-regulates quantity	0.387	ERK2 phosphorylates three serines in titin\u2019s N2B-Us: S3918, S3960, and S4010 (the latter of which is well conserved) ().	SIGNOR-279636
P19086	P28566	2	binding	up-regulates activity	0.253	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-257100
P40424	P17481	2	binding	up-regulates activity	0.499	the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.	SIGNOR-223153
P60484	Q70Z35	2	binding	down-regulates activity	0.62	Here, we used cell biology, biochemistry, and genetic approaches to show that PTEN suppresses cell movement by blocking PREX2 GEF–catalyzed activation of the GTPase RAC1. PTEN binds PREX2 and directly inhibits GEF activity.	SIGNOR-259190
Q9NPG1	P50148	2	binding	up-regulates	0.408	Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.	SIGNOR-122895
P51959	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.791	Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation.	SIGNOR-268961
P15735	P46020	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
Q9HC98	Q96AP0	1	phosphorylation	up-regulates activity	0.2	NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment\|Shelterin component TPP1 plays critical roles in chromosome end protection and telomere length regulation. Specifically, TPP1 contains an OB-fold domain that provides an interface to recruit telomerase.\|	SIGNOR-264424
Q9UP38	O00744	2	binding	up-regulates	0.664	Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6	SIGNOR-89134
Q9UGP5	P78527	0	phosphorylation	up-regulates activity	0.467	We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.	SIGNOR-273835
Q96SB4	P53671	0	phosphorylation	up-regulates activity	0.2	In vitro kinase assays revealed that LIMK2 phosphorylates SRPK1 (Fig. xref ).\|LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.	SIGNOR-279625
P06730	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.332	This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis.\|We next sought to investigate whether eIF4E ubiquitination is enhanced by the collaborative activity of cIAP1 and CHIP, which we define as both the E3 ligase activity of cIAP1 alone and the E3 ligase activity of cIAP1 and CHIP together.	SIGNOR-278669
Q15375	P52797	2	binding	up-regulates	0.802	The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion	SIGNOR-52384
P21452	P50148	2	binding	up-regulates activity	0.462	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-257015
P52954	O95863	1	transcriptional regulation	up-regulates quantity by expression	0.32	Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively	SIGNOR-266053
O76075	P42574	0	cleavage	up-regulates	0.684	Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation	SIGNOR-47419
P08754	Q13304	2	binding	up-regulates activity	0.386	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-256835
P51813	Q06187	0	phosphorylation	up-regulates	0.335	Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism.	SIGNOR-98028
P63000	Q15052	0	guanine nucleotide exchange factor	up-regulates activity	0.623	ARHGEF6 is a Rho guanine nucleotide exchange factor for Rac1 and constitutively bound to GIT1. NO and PGI2 activate PKG and PKA, respectively and both kinases phosphorylate ARHGEF6 on Ser-684 and possibly on Ser-640. Phosphorylation of ARHGEF6 results in the assembly of a GIT1-ARHGEF6–14-3-3 complex. These changes might contribute to PGI2- and NO-mediated Rac1 inhibition.	SIGNOR-272167
Q9UK32	P49841	1	phosphorylation	down-regulates activity	0.2	Moreover, RSK4 stabilized Beta-catenin in the presence of GSK-3Beta WT but not RSK4 stabilizes Beta-catenin through phosphorylation of GSK-3Beta (Ser9) in ESCC cells\|GSK-3Beta S9A in ESCC cells, which was similar to overexpression of GSK3Beta S9D\|	SIGNOR-275801
P08754	P28221	2	binding	up-regulates activity	0.435	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-256864
P49841	P17947	1	phosphorylation	down-regulates quantity by destabilization	0.2	We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7.	SIGNOR-277541

P08240

P61011

2

binding

up-regulates activity

0.2

The multi-domain SRP GTPase SRP54 recognizes the signal with its M domain and establishes the targeting complex consisting of its NG domain bound to the homologous NG domain of the SRP receptor SRα at a proximal ribosome binding site.

SIGNOR-261163

O95786

P36873

0

dephosphorylation

up-regulates activity

0.2

We identified PP1alpha and PP1gamma as primary phosphatases responsible for MDA5 and RIG-I dephosphorylation, leading to their activation.|endogenous RIG-I and MDA5 that interacted with PP1 exhibited markedly decreased phosphorylation levels at S8 and S88, respectively

SIGNOR-264580

Q15418

P50549

1

phosphorylation

up-regulates activity

0.35

Here we describe that the 90-kDa ribosomal S6 kinase 1 (RSK1), a protein kinase downstream of the extracellular signal-regulated kinase (ERK) subclass of MAPKs, binds to ER81, phosphorylates it, and enhances ER81-dependent transcription. Two in vivo RSK1 phosphorylation sites within ER81, Ser(191) and Ser(216), were identified, whose mutation to alanine reduces ER81 activity upon ERK-MAPK stimulation.

SIGNOR-249163

P45983

P30307

1

phosphorylation

down-regulates

0.411

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-164089

Q96RI0

Q03113

2

binding

up-regulates

0.485

Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13).

SIGNOR-196012

O43524

O14920

0

phosphorylation

down-regulates

0.692

Ikkbeta phosphorylates foxo3a at ser644. Ikappab kinase (ikk) physically interacts with, phosphorylates, and inhibits foxo3a independent of akt and causes proteolysis of foxo3a via the ub-dependent proteasome pathway

SIGNOR-124207

P63244

Q92615

2

binding

up-regulates activity

0.2

Here we show that LARP4B is a cytoplasmic protein that co-sediments with polysomes and accumulates upon stress induction in stress granules. Biochemical studies further show that the protein interacts with two key factors of the translational machinery, namely, the cytoplasmic poly(A) binding protein (PABPC1) and the receptor for activated C Kinase (RACK1). The biochemical and functional data of LARP4B presented in this study suggest a possible mode of action of LARP4B in translation. Assuming that LARP4B interacts with mRNA-associated PABPC1 and RACK1 simultaneously, it may form a bridge between the 3′ end of mRNAs and the initiating ribosome. This process would lead to mRNA circularization, possibly in an analogous way as it has been described for PABPC1 and eIF4G, the scaffold protein of the cap-binding complex.

SIGNOR-260941

Q9BXW9

P38398

0

ubiquitination

up-regulates activity

0.845

The major genetic evidence supporting ubiquitin ligase function for BRCA1 in vivo comes from studies on the FANCD2 protein. Whereas in wild‐type cells the FANCD2 protein co‐localizes with BRCA1 in nuclear foci and becomes monoubiquitylated in response to DNA damage, HCC1937 cells, which encode a mutated form of BRCA1, are largely defective for both monoubiquitylation of FANCD2 and foci formation

SIGNOR-263236

Q96FA3

Q9NWZ3

0

phosphorylation

up-regulates activity

0.658

The E3 ubiquitin ligase Pellino can be activated by phosphorylation in vitro, catalyzed by IL-1 receptor-associated kinase 1 (IRAK1) or IRAK4. Here, we show that phosphorylation enhances the E3 ligase activity of Pellino 1. Unusually, the full activation of Pellino 1 can be achieved by phosphorylating any one of several different sites (Ser-76, Thr-86, Thr-288, or Ser-293) or a combination of other sites (Ser-78, Thr-80, and Ser-82). Here, we show that Pellino is phosphorylated at multiple sites by IRAK1 and IRAK4 and that activation can be achieved by phosphorylating any one of several sites or a combination of other sites.

SIGNOR-276128

Q13131

P13569

1

phosphorylation

down-regulates activity

0.493

AMPK phosphorylates CFTR¬†in vitro¬†at two essential serines (Ser737and Ser768) in the R domain, formerly identified as "inhibitory" PKA sites.|Interestingly two of these sites, namely Ser737 and Ser768, have been identified as “inhibitory” R domain sites, i.e. when mutated to alanines they augment the open probability of CFTR relative to wild type|Our present results suggest that it might be AMPK rather than PKA that is phosphorylating Ser737 and Ser768 under baseline conditions

SIGNOR-259858

P11717

O60664

0

relocalization

up-regulates activity

0.725

TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.

SIGNOR-253092

Q9NPD5

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.2

PRL enhanced the binding of Stat5a to the OATP1B3 promoter and DNA-protein binding was inhibited in competition assays by excess OATP1B3 and Stat5 consensus oligomers but not by mutant Stat5 oligomers.|PRL and GH induction of Oatp1b2 and OATP1B3 promoter activity required cotransfection of Stat5a and PRLRL or GHR.

SIGNOR-268990

O15503

Q9UKV5

0

ubiquitination

down-regulates quantity by destabilization

0.525

The ubiquitination of Insig-1 is mediated by gp78 and regulated by sterols.|gp78 mediates the degradation of Insig-1 and Insig-2.

SIGNOR-278567

P09601

P69905

1

null

down-regulates activity

0.253

Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme

SIGNOR-251813

P60891

Q13131

0

phosphorylation

down-regulates activity

0.2

We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.

SIGNOR-265729

Q8IZL9

Q9UPZ9

1

phosphorylation

up-regulates

0.2

Recombinant cak1p phosphorylates thr-157 in the tdy motif of recombinant ick and activates its activity in vitro.

SIGNOR-138420

O76075

O00273

2

binding

down-regulates

0.929

Dff is a heterodimer of 40 kda and 45 kda subunits.

SIGNOR-29729

P48729

P01106

1

phosphorylation

down-regulates quantity by destabilization

0.282

Together, our findings provide evidence for CK1α-mediated destruction of c-Myc and identify c-Myc S252 as a crucial CK1α phosphorylation site for c-Myc degradation.

SIGNOR-276387

Q9UKF7

P17252

0

phosphorylation

up-regulates activity

0.319

Only BIM-I caused a reduction in 14-3-3 binding (Figure 3B), suggesting that PKC could be responsible for one or both of the serine phosphorylations, pSer274 and pSer299.

SIGNOR-273801

P32121

P32248

0

relocalization

up-regulates activity

0.377

B-Arrestin-2 is recruited to CCR7 following stimulation with CCL19, but not CCL21.

SIGNOR-278124

Q09472

Q01543

2

binding

up-regulates

0.291

P300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380

SIGNOR-202682

O60315

O00257

0

sumoylation

down-regulates quantity by destabilization

0.331

Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription.

SIGNOR-268955

P18848

P49589

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269416

O00311

O14757

0

phosphorylation

up-regulates

0.734

Chk1 directly phosphorylates essential s-phase kinases cdc7.

SIGNOR-163161

Q5D1E8

P23769

1

post transcriptional regulation

up-regulates quantity

0.2

Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA

SIGNOR-259943

Q13671

P01116

2

binding

up-regulates

0.598

We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1.

SIGNOR-113970

P61764

Q02410

2

binding

up-regulates activity

0.702

Munc18-1 is a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis. We have now identified two Munc18-1-interacting proteins called Mint1 and Mint2 that may mediate the function of Munc18-1.

SIGNOR-264035

O76094

Q9UHB9

2

binding

up-regulates activity

0.99

Taken together our data show that binding of the SRP68/72 heterodimer follows an ultrasensitive response dependent on the SRP72 C-terminus. Although the large solenoids of SRP68/72 have not been structurally characterized due to intrinsic flexibility, they serve as important contact sites in ribosome interaction.

SIGNOR-261164

P67775

Q7Z2W7

1

dephosphorylation

down-regulates activity

0.2

Using specific pharmacological and molecular tools combined with patch-clamp current recordings, we found that in heterologously expressed HEK-293 (human embryonic kidney) cells, TRPM8 channel is inhibited by the G(i) protein/adenylate cyclase (AC)/cAMP/protein kinase A (PKA) signaling cascade. We further identified the TRPM8 S9 and T17 as two key PKA phosphorylation sites regulating TRPM8 channel activity. the intracellular serine/threonine protein phosphatase 2A (PP2A) dephosphorylates TRPM8 Ser-9 and Thr-17 inhibiting the channel activity.

SIGNOR-273793

P17480

Q05195

0

transcriptional regulation

down-regulates quantity by repression

0.36

MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.

SIGNOR-269646

Q9BX66

P00519

0

phosphorylation

up-regulates activity

0.424

We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.

SIGNOR-278153

P68400

P42768

1

phosphorylation

up-regulates

0.354

Here we identify two phosphorylation sites in the vca domain of wasp at serines 483 and 484. S483 and s484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the vca domain for the arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length wasp molecule.

SIGNOR-101268

Q05655

P98082

1

phosphorylation

down-regulates

0.296

Mutational analysis revealed that a dab2 ser(24) phosphorylation mutant (s24a) abrogated the inhibitory function of dab2.

SIGNOR-127198

Q13501

P19474

0

ubiquitination

down-regulates activity

0.404

TRIM21 directly ubiquitylates p62 at residue K7 to inhibit its oligomerization and sequestration function.|TRIM21 negatively regulates p62 mediated sequestration of Keap1 and antioxidant response.

SIGNOR-278602

Q16877

Q9Y6Q9

1

phosphorylation

up-regulates activity

0.326

PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output

SIGNOR-267269

Q96RG2

P49841

1

phosphorylation

down-regulates activity

0.288

In vitro, PASK directly phosphorylates GSK3\u03b2 on its inactivating phosphorylation site Ser(9).|We conclude that PASK phosphorylates and inactivates GSK3\u03b2, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3\u03b2-mediated PDX-1 protein degradation in pancreatic \u03b2-cells.

SIGNOR-279639

Q16539

O43524

1

phosphorylation

up-regulates

0.521

Ogether, our results suggest that p38 phosphorylation of foxo3a on ser-7 is essential for its nuclear relocalization in response to doxorubicin

SIGNOR-177927

P46108

Q9Y4K4

2

binding

up-regulates activity

0.364

Two novel candidates for signalling partners of Crk family adapter proteins, the hematopoietic progenitor kinase 1 (HPK1) and the kinase homologous to SPS1/STE20 (KHS), were found to bind with great selectivity to the first SH3 domains of c-Crk and CRKL.|These results make it likely that HPK1 and KHS participate in the signal transduction of Crk family adapter proteins in certain cell types.

SIGNOR-262830

P51148

Q99698

2

binding

down-regulates activity

0.2

Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment

SIGNOR-266003

P35968

2

phosphorylation

up-regulates

0.2

Binding of vegf to the receptor induces dimerisation and autophosphorylation of specific intracellular tyrosine residues. Activation of intracellular cascades results in proliferation, migration, survival and increased permeability.

SIGNOR-157093

Q8NG06

O95786

1

ubiquitination

up-regulates activity

0.2

Specifically, the ubiquitin E3 ligase TRIM25 ubiquitinates K172 in the CARD2 of RIG-I, which is essential for the efficient interaction of RIG-I with MAVS and thereby for antiviral signal transduction

SIGNOR-264582

O95835

Q7L9L4

2

binding

up-regulates

0.921

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-169795

O00141

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.292

These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.

SIGNOR-264543

O95352

Q9GZQ8

2

binding

up-regulates

0.873

These results indicated that the fap motif of atg7 is indispensable for formation of the atg3-lc3 e2-substrate intermediate through the interaction of atg7 with atg3.

SIGNOR-195239

O94907

P50553

0

transcriptional regulation

down-regulates quantity by repression

0.306

We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.

SIGNOR-245885

P35568

P45984

0

phosphorylation

down-regulates

0.706

Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632

SIGNOR-118877

Q712K3

P19784

0

phosphorylation

up-regulates activity

0.449

UBC3B is specifically phosphorylated by CK2 in vitro and in vivo. We mapped by deletions and site directed mutagenesis the phosphorylation site to a serine residue within the C-terminal domain in position 233 of UBC3B and in the corresponding serine residue of UBC3. | Following CK2-dependent phosphorylation both UBC3B and UBC3 bind to the F-box protein beta-TrCP, the substrate recognition subunit of an SCF (Skp1, Cul1, F-box) ubiquitin ligase. Furthermore, we observed that co-transfection of CK2alpha' together with UBC3B, but not with UBC3DeltaC, enhances the degradation of beta-catenin.

SIGNOR-251047

Q13324

P06850

2

binding

up-regulates activity

0.917

The actions of CRH are transduced through CRH receptors, which belong to the class II/secretin-like family of the G-protein coupled receptor (GPCR) superfamily (Martin et al. 2005). There are three types of CRH receptors – type 1 (CRHR1), type 2 (CRHR2) and type 3 (CRHR3). Among these, CRHR3 has not been identified in mammals. |CRH is a high-affinity ligand of CRHR1. It also binds to CRHR2, but with lower affinity

SIGNOR-268611

P45983

P04637

1

phosphorylation

up-regulates

0.796

Activated jnk phosphorylates p53

SIGNOR-59812

P16220

P35680

2

binding

up-regulates activity

0.373

The mammalian two-hybrid system showed that the region aa 393 to 476 of LFB3 is involved in the interaction with CREB or ATF1. The importance of this region for mediating cAMP induction was confirmed in transient transfection assays.

SIGNOR-241323

P04150

P28562

1

null

up-regulates quantity

0.58

Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1|Both induction of MKP-1 expression and inhibition of its degradation are necessary for glucocorticoid-mediated inhibition of Erk-1/2 activation. In NIH-3T3 fibroblasts, although glucocorticoids up-regulate the MKP-1 level, they do not attenuate the proteasomal degradation of this protein and consequently they are unable to inhibit Erk-1/2 activity.

SIGNOR-253546

Q96Q05

O14920

2

binding

up-regulates activity

0.489

We demonstrated by immunohistochemistry that NIBP expression in the brain is localized to neurons. NIBP physically interacts with NIK, IKK(beta), but not IKK(alpha) or IKK(gamma). NIBP overexpression potentiates tumor necrosis factor-alpha-induced NF-kappaB activation through increased phosphorylation of the IKK complex and its downstream I(kappa)B(alpha) and p65 substrates.

SIGNOR-269673

P54646

P54619

2

binding

up-regulates

0.897

Gamma non-catalytic subunit mediates binding to amp, adp and atp, leading to activate or inhibit ampk: amp-binding results in allosteric activation of alpha catalytic subunit (prkaa1 or prkaa2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits.

SIGNOR-139173

Q86X55

P53778

0

phosphorylation

down-regulates activity

0.363

Here, we identify a role for the mitogen-activated protein kinase (MAPK) p38g/MAPK12 as a critical regulator of satellite stem cell fate through phosphorylation of Carm1.

SIGNOR-255897

P06493

P30304

2

phosphorylation

up-regulates

0.842

Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.

SIGNOR-95260

Q15382

Q8IW41

0

phosphorylation

down-regulates activity

0.401

Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation.

SIGNOR-276313

P24941

Q08050

1

phosphorylation

up-regulates activity

0.75

We demonstrated that FoxM1B transcriptional activity requires binding of either S-phase or M-phase Cdk-cyclin complexes to mediate efficient Cdk phosphorylation of the FoxM1B Thr 596 residue, which is essential for recruitment of p300/CBP coactivator proteins.

SIGNOR-250731

P29353

Q13588

2

binding

up-regulates

0.506

T cell activation effects an increase in grap association with p36/38, shc, sos, and dynamin.

SIGNOR-45528

P53350

P41279

0

phosphorylation

up-regulates

0.2

Xplkk1 phosphorylates and activates mammalian plk / xplkk1 phosphorylates thr-210

SIGNOR-92274

Q9UGI0

Q15672

1

deubiquitination

down-regulates activity

0.331

Trabid inhibits Twist1 activity by cleaving RNF8-mediated Twist1 K63-linked ubiquitination

SIGNOR-273502

Q13950

P06493

0

phosphorylation

up-regulates

0.479

In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.

SIGNOR-143586

O15198

O00238

0

phosphorylation

up-regulates activity

0.708

Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.

SIGNOR-255264

Q9UHD2

Q92985

1

phosphorylation

up-regulates activity

0.768

In most cell types, IRF7 is phosphorylated and activated by IKK\u03b5 and TBK1 after viral infection.|We found that phosphorylation of IRF7 on Ser477 and Ser479 by IKK\u03b5 or TBK1 is inhibited by ORF45.

SIGNOR-278216

Q06830

P00519

0

phosphorylation

down-regulates activity

0.387

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-276278

Q16576

Q13131

0

phosphorylation

up-regulates activity

0.2

AMPK increased HAT1 activity through phosphorylation of HAT1-Ser190 and RBBP7-Ser314| interaction between RBBP7 and HAT1 is required for acetyltransferase activity

SIGNOR-264784

P31152

Q05923

2

phosphorylation

up-regulates activity

0.353

However, co-expression of ERK4 significantly increased the half-life of DUSP2 (XREF_FIG).|In support of the latter notion we have shown that wild-type ERK4 can phosphorylate DUSP2 in vitro and future studies will be aimed at identifying the relevant site (s) of modification and determining their influence on DUSP2 stability.

SIGNOR-278959

P27037

P13385

2

binding

down-regulates

0.642

Here we show that cripto can form a complex with activin and actrii/iib cripto inhibited crosslinking of activin to alk4 and the association of alk4 with actrii/iib.

SIGNOR-100052

Q9Y566

Q9P1A6

0

relocalization

up-regulates activity

0.756

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264589

O95747

Q96J92

0

phosphorylation

up-regulates activity

0.48

In addition, WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylate and activate NCC [ xref ; xref ].|Later studies also indicate that WNK4 phosphorylates and activates Ste20-type kinases SPAK and OSR1, which in turn phosphorylates and activates NCC ; ].

SIGNOR-278389

O94916

P29350

0

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

Q99684

P14921

2

binding

down-regulates activity

0.426

Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.

SIGNOR-254201

Q9Y4X5

O60573

1

ubiquitination

down-regulates quantity by destabilization

0.678

Human homologue of Drosophila ariadne (HHARI) is a RING-IBR-RING domain protein identified through its ability to bind the human ubiquitin-conjugating enzyme, UbcH7. Thus, by promoting the ubiquitin-mediated degradation of 4EHP, HHARI may have a role in both protein degradation and protein translation.

SIGNOR-268848

P10915

P08254

0

cleavage

down-regulates quantity by destabilization

0.384

Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.

SIGNOR-256330

P26447

O94916

0

transcriptional regulation

up-regulates quantity by expression

0.478

As expected, the depletion of NFAT5 decreased the S100A4 and LCN2 mRNA levels (Figure 3a). In addition, chromatin immunoprecipitation (ChIP) assay using NFAT5 antibody indicated that NFAT5 was bound to the S100A4 and LCN2 promoters (Figure 3b, Supplementary Figure S3), as expected (Chen et al., 2009).

SIGNOR-274115

P10721

P29350

2

binding

down-regulates

0.576

Shp-1 binds and negatively modulates the c-kit receptor by interaction with tyrosine 569 in the c-kit juxtamembrane domain.

SIGNOR-56104

P19086

Q99677

2

binding

up-regulates activity

0.2

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-257325

P19174

P16520

2

binding

up-regulates

0.2

Furthermore, this work suggested that the g subunits released upon gi activation activated phospholipase c (plc- ) to produce inositol 3-phosphate (ip3), which would subsequently increase intracellular ca2+ abundance.

SIGNOR-199135

Q13224

P17612

0

phosphorylation

up-regulates activity

0.414

Here we identify serine residue 1166 (Ser1166) in the carboxy-terminal tail of the NMDAR subunit GluN2B to be a direct molecular and functional target of PKA phosphorylation critical to NMDAR-dependent Ca(2+) permeation and Ca(2+) signaling in spines.

SIGNOR-276616

P28482

Q8WZ42

1

phosphorylation

up-regulates quantity

0.387

ERK2 phosphorylates three serines in titin\u2019s N2B-Us: S3918, S3960, and S4010 (the latter of which is well conserved) ().

SIGNOR-279636

P19086

P28566

2

binding

up-regulates activity

0.253

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-257100

P40424

P17481

2

binding

up-regulates activity

0.499

the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms.

SIGNOR-223153

P60484

Q70Z35

2

binding

down-regulates activity

0.62

Here, we used cell biology, biochemistry, and genetic approaches to show that PTEN suppresses cell movement by blocking PREX2 GEF–catalyzed activation of the GTPase RAC1. PTEN binds PREX2 and directly inhibits GEF activity.

SIGNOR-259190

Q9NPG1

P50148

2

binding

up-regulates

0.408

Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.

SIGNOR-122895

P51959

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.791

Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation.

SIGNOR-268961

P15735

P46020

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

Q9HC98

Q96AP0

1

phosphorylation

up-regulates activity

0.2

NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment|Shelterin component TPP1 plays critical roles in chromosome end protection and telomere length regulation. Specifically, TPP1 contains an OB-fold domain that provides an interface to recruit telomerase.|

SIGNOR-264424

Q9UP38

O00744

2

binding

up-regulates

0.664

Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6

SIGNOR-89134

Q9UGP5

P78527

0

phosphorylation

up-regulates activity

0.467

We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.

SIGNOR-273835

Q96SB4

P53671

0

phosphorylation

up-regulates activity

0.2

In vitro kinase assays revealed that LIMK2 phosphorylates SRPK1 (Fig. xref ).|LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.

SIGNOR-279625

P06730

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.332

This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis.|We next sought to investigate whether eIF4E ubiquitination is enhanced by the collaborative activity of cIAP1 and CHIP, which we define as both the E3 ligase activity of cIAP1 alone and the E3 ligase activity of cIAP1 and CHIP together.

SIGNOR-278669

Q15375

P52797

2

binding

up-regulates

0.802

The activation of eph receptors by their ligands, which are membrane-anchored molecules, involves a cell-cell recognition event that often causes cell repulsion

SIGNOR-52384

P21452

P50148

2

binding

up-regulates activity

0.462

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-257015

P52954

O95863

1

transcriptional regulation

up-regulates quantity by expression

0.32

Compared with the empty vector, LBX1 induced increased promoter activity of threefold to fourfold and fivefold to sixfold for ZEB1 and Snail1, respectively

SIGNOR-266053

O76075

P42574

0

cleavage

up-regulates

0.684

Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation

SIGNOR-47419

P08754

Q13304

2

binding

up-regulates activity

0.386

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-256835

P51813

Q06187

0

phosphorylation

up-regulates

0.335

Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism.

SIGNOR-98028

P63000

Q15052

0

guanine nucleotide exchange factor

up-regulates activity

0.623

ARHGEF6 is a Rho guanine nucleotide exchange factor for Rac1 and constitutively bound to GIT1. NO and PGI2 activate PKG and PKA, respectively and both kinases phosphorylate ARHGEF6 on Ser-684 and possibly on Ser-640. Phosphorylation of ARHGEF6 results in the assembly of a GIT1-ARHGEF6–14-3-3 complex. These changes might contribute to PGI2- and NO-mediated Rac1 inhibition.

SIGNOR-272167

Q9UK32

P49841

1

phosphorylation

down-regulates activity

0.2

Moreover, RSK4 stabilized Beta-catenin in the presence of GSK-3Beta WT but not RSK4 stabilizes Beta-catenin through phosphorylation of GSK-3Beta (Ser9) in ESCC cells|GSK-3Beta S9A in ESCC cells, which was similar to overexpression of GSK3Beta S9D|

SIGNOR-275801

P08754

P28221

2

binding

up-regulates activity

0.435

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-256864

P49841

P17947

1

phosphorylation

down-regulates quantity by destabilization

0.2

We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7.

SIGNOR-277541