GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 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
Q13131	O43524	1	phosphorylation	up-regulates activity	0.517	Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization.	SIGNOR-249684
P00519	P42684	1	phosphorylation	up-regulates	0.517	The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization	SIGNOR-134396
Q96GD4	O95239	1	phosphorylation	up-regulates activity	0.517	Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.	SIGNOR-265992
Q99500	P50148	1	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
P31749	Q15121	1	phosphorylation	up-regulates activity	0.517	Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.	SIGNOR-102092
Q9NYA4	P84022	1	dephosphorylation	down-regulates	0.517	Here we demonstrate that myotubularin-related protein 4	SIGNOR-163034
O75636	O00187	1	binding	up-regulates activity	0.517	In the lectin pathway, mannose-binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated serine protease-2 (MASP-2)	SIGNOR-263412
Q15139	Q9UQL6	1	phosphorylation	down-regulates activity	0.516	Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes.	SIGNOR-249270
Q9H3N8	P63096	1	binding	up-regulates activity	0.516	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-256672
P29275	P63092	1	binding	up-regulates activity	0.516	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256767
Q92633	P08754	1	binding	up-regulates activity	0.516	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-256839
Q99835	P63096	1	binding	up-regulates	0.516	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-199159
Q96J02	O95835	1	ubiquitination	down-regulates quantity by destabilization	0.516	Furthermore, ITCH mediated degradation of LATS1 was associated with enhanced cell growth, induction of epithelial-mesenchymal transition, and increased tumorigenicity.\|Ubiquitination of LATS1 catalyzed by ITCH stimulated the proteasomal degradation of LATS1.	SIGNOR-278816
P48729	P27348	1	phosphorylation	down-regulates activity	0.516	This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.	SIGNOR-250795
Q00535	Q05193	1	phosphorylation	up-regulates activity	0.516	Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE.	SIGNOR-250661
P00533	O14939	1	phosphorylation	up-regulates activity	0.516	Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF). PLD2, but not PLD1, associates with the EGF receptor in a ligand-independent manner and becomes tyrosine-phosphorylated upon EGF receptor activation. Tyrosine 11 (Tyr-11) of PLD2 was identified as the specific phosphorylation site. Mutation of this residue to phenylalanine enhanced basal activity almost 2-fold	SIGNOR-251095
Q9UQF2	Q12852	1	binding	down-regulates	0.516	Jip inhibits dlk dimerization.	SIGNOR-109046
Q9NRM7	Q4VCS5	1	phosphorylation	up-regulates quantity by stabilization	0.516	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-275846
P03372	P11511	1	transcriptional regulation	down-regulates quantity by repression	0.516	By binding to S1, ERalpha down-regulates the aromatase promoter activity.	SIGNOR-271683
Q01718	P63092	1	binding	up-regulates activity	0.516	The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins	SIGNOR-268694
P17612	Q04206	1	phosphorylation	up-regulates	0.516	The transcriptional activity of nf-kappa b is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase a (pka).	SIGNOR-58972
Q13145	O14641	1	binding	up-regulates	0.516	Bmp-2 mediates phosphorylated smad1 (psmad1) or, with loss of bmprii, psmad3-dependent recruitment of disheveled (dvl) to promote rhoa-rac1 signaling necessary for motility.	SIGNOR-23037
Q96L34	Q5BJF6	1	phosphorylation	up-regulates activity	0.516	Collectively, our data indicate that MARK4 interacts with ODF2 in vivo and phosphorylates ODF2 in vitro.\|Collectively, our data support the model that MARK4 promotes ciliogenesis by acting upstream of ODF2.	SIGNOR-278961
O14965	P41208	1	phosphorylation	up-regulates	0.516	Our studies show that aurora a phosphorylates centrin at serine 170 in vitro and that the serine 170 phosphorylation affects the stability of centrin by regulating its interaction with apc/c. finally we demonstrated that phosphorylation of centrin serine 170 is an absolute requirement for aurora a-mediated centriole amplification.	SIGNOR-174686
O14522	P40763	1	dephosphorylation	down-regulates activity	0.516	Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T\|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.	SIGNOR-263981
P18031	Q14247	1	dephosphorylation	up-regulates activity	0.516	We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.	SIGNOR-277027
Q5VT25	P24844	1	phosphorylation	up-regulates	0.516	More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.	SIGNOR-188781
Q13554	P16949	1	phosphorylation	down-regulates	0.515	Stimulation via cd2 activated multiple signal transduction pathways, resulting in phosphorylation of distinct sites of stathmin. Ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells.	SIGNOR-59358
Q9GZU7	Q15796	1	dephosphorylation	down-regulates activity	0.515	SCP1 Dephosphorylates Smad2/3 in the Linkers\|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity	SIGNOR-248795
O15169	Q13233	1	binding	up-regulates	0.515	We found that in contrast to axin, dvl2 activation of jnk does not require mekk1.	SIGNOR-77591
Q15349	P32004	1	phosphorylation	up-regulates activity	0.515	Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. \| These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152.	SIGNOR-248949
P49757	P04637	1	binding	up-regulates	0.515	Numb can actually interact in vivo with endogenous mdm2 and p53, resulting in a trimeric complex between the three proteins [10]. This interaction appears to regulate the stability of p53, as reduction of numb levels by rna interference (rnai) causes a decrease in the half-life of p53 and consequently a reduction in steady-state levels of the protein. Consistent with this observation, overexpression of numb increases the level of p53 in both unstressed and stressed cells.	SIGNOR-178668
P31749	Q13309	1	phosphorylation	down-regulates activity	0.515	We further show that Akt1 phosphorylates Skp2 at Ser72, which is required to disrupt the interaction between Cdh1 and Skp2.	SIGNOR-278274
Q16514	P17544	1	binding	up-regulates activity	0.515	We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7.	SIGNOR-225249
O43525	O43526	2	binding	up-regulates activity	0.515	The M-current regulates the subthreshold electrical excitability of many neurons, determining their firing properties and responsiveness to synaptic input. To date, however, the genes that encode subunits of this important channel have not been identified. The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.	SIGNOR-268832
O43526	O43525	2	binding	up-regulates activity	0.515	The M-current regulates the subthreshold electrical excitability of many neurons, determining their firing properties and responsiveness to synaptic input. To date, however, the genes that encode subunits of this important channel have not been identified. The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.	SIGNOR-268833
P21127	O00303	1	phosphorylation	up-regulates activity	0.515	EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.\|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis.	SIGNOR-273133
O60674	Q9UQC2	1	phosphorylation	up-regulates	0.515	In vitro, activated jak2 directly phosphorylated specific gab2 tyrosine residues. Mutagenesis studies revealed that gab2 tyrosine 643 (y643) was a major target of jak2 in vitro, and a key residue for jak2-dependent phosphorylation in intact cells. Mutation of gab2 y643 inhibited g-csf-stimulated erk1/2 activation and shp2 binding to gab2.	SIGNOR-179488
P49841	O75122	1	phosphorylation	down-regulates activity	0.515	GSK-3beta directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules.\| CLASPs were originally identified as CLIP-170-interacting proteins and later found to be required for microtubule stabilisation at the cortical regions of epithelial cells	SIGNOR-264826
P24941	O43303	1	phosphorylation	down-regulates activity	0.515	GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)	SIGNOR-265956
O96017	P18887	1	phosphorylation	up-regulates	0.515	Chk2 formed a complex with xrcc1, the ber scaffold protein, and phosphorylated xrcc1 in vivo and in vitro at thr(284). our results are consistent with the phosphorylation of xrcc1 by atm-chk2 facilitating recruitment of downstream ber proteins to the initial damage recognition/excision step to promote ber.	SIGNOR-181816
P00519	P29323	1	phosphorylation	down-regulates	0.515	Two-hybrid screens identified regions of abl and arg that bind to the ephb2 and epha4 receptors, suggesting a novel signaling connection involving the two kinase families.The connection between EphB2 and Abl/Arg appears to be reciprocal. Activated EphB2 causes tyrosine phosphorylation of Abl and Arg, and vice versa. Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl.	SIGNOR-109668
Q05655	P04792	1	phosphorylation	down-regulates activity	0.515	Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B).	SIGNOR-278425
Q9Y2H9	P60484	1	phosphorylation	down-regulates	0.515	Mast1 was found to associate to pten.	SIGNOR-138003
Q9ULT6	Q13467	1	ubiquitination	down-regulates quantity	0.515	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260118
O43318	Q15653	1	phosphorylation	down-regulates	0.515	Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene.	SIGNOR-55719
Q5S007	O95295	1	phosphorylation	down-regulates	0.514	Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2	SIGNOR-202436
Q14980	P68366	1	binding	up-regulates	0.514	Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.	SIGNOR-116788
Q14157	P35226	1	binding	up-regulates activity	0.514	We identified UBAP2L as a novel BMI1-interacting protein. UBAP2L, BMI1, RNF2, and PHC1 define a novel Polycomb subcomplex	SIGNOR-261315
Q13501	P00441	1	binding	down-regulates quantity by destabilization	0.514	This study provides a novel molecular mechanism by which mutant SOD1 can be recognized by p62 in an ubiquitin-independent fashion and targeted for the autophagy-lysosome degradation pathway.	SIGNOR-262801
Q8IUQ4	Q9H2X6	1	polyubiquitination	down-regulates quantity by destabilization	0.514	Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation.	SIGNOR-276166
P18146	P78337	1	binding	up-regulates activity	0.514	GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.	SIGNOR-254916
P31751	P16220	1	phosphorylation	up-regulates	0.514	Creb is a nuclear target for activation via the growth factor-dependent ser/thr kinase akt/pkb. When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp.	SIGNOR-62253
Q13627	P08151	1	phosphorylation	up-regulates activity	0.514	Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.\|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .	SIGNOR-278930
P68400	P37840	1	phosphorylation	up-regulates	0.514	In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.	SIGNOR-73807
P42336	Q06187	1	phosphorylation	up-regulates activity	0.514	Activation of Btk occurs by transphosphorylation of tyrosine 551 in the catalytic domain, resulting in a dramatic increase in the catalytic activity of the kinase (11, 12, 13). This allows for autophosphorylation at tyrosine 223 in the SH3 domain (14). Both Lyn and Syk have been demonstrated to be involved in BCR-mediated Btk activation (11), but processes that drive colocalization of these kinases are ill-defined. Recently, it was suggested that phosphatidylinositol 3-kinase (PI3-K) is also involved in Btk activation	SIGNOR-249610
P67775	Q9BUB5	1	dephosphorylation	down-regulates	0.514	Moreover, a dephosphorylation assay revealed that pp2a could directly dephosphorylate mnk1 and eif4e.	SIGNOR-168314
Q969G2	P28069	1	transcriptional regulation	up-regulates quantity by expression	0.514	We show that normal LHX4 binds to a human-specific element and subsequently activates transcription from the proximal upstream regulatory sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known as the main regulator of GH expression.	SIGNOR-266056
Q8WZ64	P61586	1	gtpase-activating protein	down-regulates activity	0.514	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260453
P31749	P15976	1	phosphorylation	up-regulates	0.514	We found that akt directly phosphorylates the transcription factor gata-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the timp-1 promoter.	SIGNOR-139782
P35372	P08754	1	binding	up-regulates activity	0.513	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-256854
P00533	P37231	1	phosphorylation	down-regulates quantity by destabilization	0.513	Here, we found that nuclear EGFR induced phosphorylation of PPARγ at Tyr-74 leading to PPARγ ubiquitination and degradation by mouse double minute 2 (MDM2) ubiquitin ligase.	SIGNOR-277190
P06493	Q96GX5	1	phosphorylation	up-regulates activity	0.513	We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop	SIGNOR-249653
P12931	P35916	1	phosphorylation	up-regulates	0.513	Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk.	SIGNOR-165035
P28482	O60674	1	phosphorylation	down-regulates	0.513	We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner	SIGNOR-236331
P28482	Q13362	2	phosphorylation	down-regulates	0.513	Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.	SIGNOR-144313
Q13362	P28482	2	binding	down-regulates	0.513	B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk	SIGNOR-144325
P00519	P55211	1	phosphorylation	up-regulates	0.513	C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.	SIGNOR-133260
P78527	P00519	1	phosphorylation	up-regulates activity	0.513	We show that DNA-PK phosphorylates and activates c-Abl in vitro.	SIGNOR-279268
Q15418	O00418	1	phosphorylation	down-regulates activity	0.513	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity	SIGNOR-109708
P31751	Q86YS7	1	phosphorylation	up-regulates activity	0.513	MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).	SIGNOR-279585
Q9UQM7	Q00613	1	phosphorylation	up-regulates activity	0.513	Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells.	SIGNOR-250631
P06493	P63279	1	phosphorylation	up-regulates activity	0.512	Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71.	SIGNOR-278174
Q13177	P35240	1	phosphorylation	down-regulates	0.512	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159768
Q9P107	P60953	1	gtpase-activating protein	down-regulates activity	0.512	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260507
Q8WWQ0	P35568	1	binding	up-regulates activity	0.512	We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner.	SIGNOR-266962
Q92748	Q9NPA3	1	binding	down-regulates activity	0.512	In the current study, we have determined the crystal structure of mouse S14 to 2.65-Å resolution. The structure of S14 reveals a helical protein arranged as a symmetric dimer. Cultured cell experiments indicate that S14 can form heterodimers with MIG12, suggesting a mechanism through which S14 could modulate ACC activity and subsequently rates of fatty acid synthesis via heterodimer formation with MIG12.In the current study, we have shown that regulating the levels of S14∶MIG12 heterodimers regulates the ability of MIG12 to activate ACC. Increasing S14∶MIG12 heterodimers by the overexpression of S14 resulted in decreased ACC activity and polymerization, whereas decreasing S14∶MIG12 heterodimers by knockdown of S14 increased ACC activity and polymerization.	SIGNOR-267113
P15173	Q969P5	1	binding	down-regulates activity	0.512	Myogenin had a MAFbx-recognition motif and interacted with MAFbx. MAFbx activated polyubiquitination of myogenin. The results of this study suggest that MAFbx functions as an F-box protein for ubiquitination of myogenin.	SIGNOR-237854
P47871	P63092	1	binding	up-regulates activity	0.512	Glucagon signals through its receptor on the cell surface (Fig.1). The binding of glucagon to the extracellular loops of the glucagon receptor results in conformational changes of the latter, leading to subsequent activation of the coupled G proteins. At least two classes of G proteins are known to be associated with and involved in the signal transduction of the glucagon receptor, namely Gsα and Gq. The activation of Gsα leads to activation of adenylate cyclase, increase in intracellular cAMP levels, and subsequent activation of protein kinase A (PKA).	SIGNOR-267715
Q13315	Q13541	1	phosphorylation	down-regulates	0.512	Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e.	SIGNOR-85619
Q13315	Q7LG56	1	phosphorylation	up-regulates	0.512	Atm-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53r2 protein against mdm2 to dna damage	SIGNOR-182423
P30556	P29992	1	binding	up-regulates activity	0.512	The angiotensin II type 1 receptor (AT1 R) is a G q/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney.	SIGNOR-278125
Q99996	Q15642	1	binding	up-regulates activity	0.512	Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues.\|Co-immunoprecipitation assay revealed that AKAP-9 and CIP4 physically interacted with each other in Lovo and HT29 cells (Fig. 4B and C).	SIGNOR-260303
Q14012	P18846	1	phosphorylation	up-regulates activity	0.512	Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.	SIGNOR-250611
Q99986	P05412	1	phosphorylation	up-regulates	0.512	Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription	SIGNOR-127073
P17612	O14965	1	phosphorylation	up-regulates activity	0.512	Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.	SIGNOR-250337
Q9NQC7	P20749	1	deubiquitination	down-regulates	0.512	Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.	SIGNOR-146774
P45983	P19419	1	phosphorylation	up-regulates activity	0.512	However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.	SIGNOR-236432
P22681	O94875	1	ubiquitination	down-regulates	0.512	Cbl-argbp2 complex mediates ubiquitination and degradation of c-abl	SIGNOR-96325
P15863	P50221	1	binding	up-regulates activity	0.512	We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.	SIGNOR-222193
Q06124	P32927	1	dephosphorylation	up-regulates	0.511	Shp2 is thought to act as a positive mediator of growth factor signals.. Hp2 could act as an adaptor between the activated c and grb2, thus leading to activation of the ras/mitogen-activated protein kinase pathway, known to be activated by il-3	SIGNOR-48557
Q16539	P04150	1	phosphorylation	up-regulates	0.511	We found serine 211 of the human gr to be a substrate for p38 mapk both in vitro and intracellularly. Mutation of this site to alanine greatly diminished gr-driven gene transcription and apoptosis.	SIGNOR-135198
Q96EB6	P23025	1	deacetylation	up-regulates activity	0.511	SIRT1 deacetylates XPA at residues K63, K67, and K215 to promote interactions with ATR	SIGNOR-262294
O15111	P42345	1	phosphorylation	up-regulates activity	0.511	In those studies, we found that IKKalpha interacts with and phosphorylates mTOR in the mTORC1 complex to activate mTORC1, and that Akt signaling drives the IKKalpha-mTORC1 interaction.\|We then studied whether IKKalpha promotes Akt and mTOR activity in other mammalian cancer cell lines.	SIGNOR-279607
O43293	O14950	1	phosphorylation	up-regulates	0.511	Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.	SIGNOR-16043
P08754	O43306	1	binding	down-regulates activity	0.511	Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3	SIGNOR-278079
Q9HBE1	P78317	1	binding	down-regulates	0.511	In vitro and in vivo interaction between rnf4 and patz was demonstrated / patz acted as a transcriptional repressor, whereas its partner rnf4 behaved as a transcriptional activator./ the association of patz with rnf4 switches activation to repression	SIGNOR-75775
P28482	Q13485	1	phosphorylation	up-regulates	0.511	Phosphorylation of thr276 is shown to be important for tgf-?-Induced nuclear accumulation and, as a consequence, transcriptional activity of smad4. these results suggest that smad4 can be phosphorylated by erk2 at thr276.	SIGNOR-101660
P06493	Q12778	1	phosphorylation	down-regulates	0.511	Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1.	SIGNOR-178202
O00230	Q96LB1	1	binding	up-regulates	0.511	The mrgx2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin n-terminal peptides (pamp)	SIGNOR-139855

Q13131

O43524

1

phosphorylation

up-regulates activity

0.517

Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization.

SIGNOR-249684

P00519

P42684

1

phosphorylation

up-regulates

0.517

The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization

SIGNOR-134396

Q96GD4

O95239

1

phosphorylation

up-regulates activity

0.517

Using in vitro kinase assays, we found that active AMPK and Aurora B phosphorylated KIF4A at Ser801 and Thr799 respectively in a time-dependent manner (Figure 5D). KIF4A is phosphoregulated by AMPK and Aurora B. Although AMPK phosphorylation increased the ATPase activity of KIF4A, Aurora B phosphorylation resulted in a stronger increase (Figure 5I), which might be consistent with the more powerful kinase function of Aurora B during mitosis.

SIGNOR-265992

Q99500

P50148

1

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

P31749

Q15121

1

phosphorylation

up-regulates activity

0.517

Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.

SIGNOR-102092

Q9NYA4

P84022

1

dephosphorylation

down-regulates

0.517

Here we demonstrate that myotubularin-related protein 4

SIGNOR-163034

O75636

O00187

1

binding

up-regulates activity

0.517

In the lectin pathway, mannose-binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated serine protease-2 (MASP-2)

SIGNOR-263412

Q15139

Q9UQL6

1

phosphorylation

down-regulates activity

0.516

Here, we demonstrate that signaling by protein kinase C (PKC) is sufficient and, in some cases, necessary to drive nuclear export of class II HDAC5 in cardiomyocytes.

SIGNOR-249270

Q9H3N8

P63096

1

binding

up-regulates activity

0.516

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-256672

P29275

P63092

1

binding

up-regulates activity

0.516

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256767

Q92633

P08754

1

binding

up-regulates activity

0.516

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-256839

Q99835

P63096

1

binding

up-regulates

0.516

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-199159

Q96J02

O95835

1

ubiquitination

down-regulates quantity by destabilization

0.516

Furthermore, ITCH mediated degradation of LATS1 was associated with enhanced cell growth, induction of epithelial-mesenchymal transition, and increased tumorigenicity.|Ubiquitination of LATS1 catalyzed by ITCH stimulated the proteasomal degradation of LATS1.

SIGNOR-278816

P48729

P27348

1

phosphorylation

down-regulates activity

0.516

This protein kinase has been identified as casein kinase Ialpha (CKIalpha) by peptide mapping analysis and sequencing. Among mammalian 14-3-3, only 14-3-3 tau possesses a phosphorylatable residue at the same position (Ser-233), and we show that this residue is also phosphorylated by CKI. In addition, we show that 14-3-3 zeta is exclusively phosphorylated on Thr-233 in human embryonic kidney 293 cells. The residue 233 is located within a region shown to be important for the association of 14-3-3 to target proteins.

SIGNOR-250795

Q00535

Q05193

1

phosphorylation

up-regulates activity

0.516

Here, we show that cyclin-dependent kinase 5 (Cdk5) phosphorylates dynamin I on Ser 774 and Ser 778 in vitro, which are identical to its endogenous phosphorylation sites in vivo. Cdk5 antagonists and expression of dominant-negative Cdk5 block phosphorylation of dynamin I, but not of amphiphysin or AP180, in nerve terminals and inhibit SVE.

SIGNOR-250661

P00533

O14939

1

phosphorylation

up-regulates activity

0.516

Using transiently transfected human embryonic kidney fibroblasts (HEK293), we demonstrate here that PLD1 activity, and to a lesser extent PLD2 activity, is stimulated in response to epidermal growth factor (EGF). PLD2, but not PLD1, associates with the EGF receptor in a ligand-independent manner and becomes tyrosine-phosphorylated upon EGF receptor activation. Tyrosine 11 (Tyr-11) of PLD2 was identified as the specific phosphorylation site. Mutation of this residue to phenylalanine enhanced basal activity almost 2-fold

SIGNOR-251095

Q9UQF2

Q12852

1

binding

down-regulates

0.516

Jip inhibits dlk dimerization.

SIGNOR-109046

Q9NRM7

Q4VCS5

1

phosphorylation

up-regulates quantity by stabilization

0.516

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-275846

P03372

P11511

1

transcriptional regulation

down-regulates quantity by repression

0.516

By binding to S1, ERalpha down-regulates the aromatase promoter activity.

SIGNOR-271683

Q01718

P63092

1

binding

up-regulates activity

0.516

The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins

SIGNOR-268694

P17612

Q04206

1

phosphorylation

up-regulates

0.516

The transcriptional activity of nf-kappa b is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase a (pka).

SIGNOR-58972

Q13145

O14641

1

binding

up-regulates

0.516

Bmp-2 mediates phosphorylated smad1 (psmad1) or, with loss of bmprii, psmad3-dependent recruitment of disheveled (dvl) to promote rhoa-rac1 signaling necessary for motility.

SIGNOR-23037

Q96L34

Q5BJF6

1

phosphorylation

up-regulates activity

0.516

Collectively, our data indicate that MARK4 interacts with ODF2 in vivo and phosphorylates ODF2 in vitro.|Collectively, our data support the model that MARK4 promotes ciliogenesis by acting upstream of ODF2.

SIGNOR-278961

O14965

P41208

1

phosphorylation

up-regulates

0.516

Our studies show that aurora a phosphorylates centrin at serine 170 in vitro and that the serine 170 phosphorylation affects the stability of centrin by regulating its interaction with apc/c. finally we demonstrated that phosphorylation of centrin serine 170 is an absolute requirement for aurora a-mediated centriole amplification.

SIGNOR-174686

O14522

P40763

1

dephosphorylation

down-regulates activity

0.516

Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T|Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

SIGNOR-263981

P18031

Q14247

1

dephosphorylation

up-regulates activity

0.516

We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.

SIGNOR-277027

Q5VT25

P24844

1

phosphorylation

up-regulates

0.516

More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.

SIGNOR-188781

Q13554

P16949

1

phosphorylation

down-regulates

0.515

Stimulation via cd2 activated multiple signal transduction pathways, resulting in phosphorylation of distinct sites of stathmin. Ser16 of recombinant human stathmin was phosphorylated also by purified cam kinase ii, and in vivo, cam kinase ii activity was indeed stimulated in cd2-triggered jurkat cells.

SIGNOR-59358

Q9GZU7

Q15796

1

dephosphorylation

down-regulates activity

0.515

SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity

SIGNOR-248795

O15169

Q13233

1

binding

up-regulates

0.515

We found that in contrast to axin, dvl2 activation of jnk does not require mekk1.

SIGNOR-77591

Q15349

P32004

1

phosphorylation

up-regulates activity

0.515

Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. | These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152.

SIGNOR-248949

P49757

P04637

1

binding

up-regulates

0.515

Numb can actually interact in vivo with endogenous mdm2 and p53, resulting in a trimeric complex between the three proteins [10]. This interaction appears to regulate the stability of p53, as reduction of numb levels by rna interference (rnai) causes a decrease in the half-life of p53 and consequently a reduction in steady-state levels of the protein. Consistent with this observation, overexpression of numb increases the level of p53 in both unstressed and stressed cells.

SIGNOR-178668

P31749

Q13309

1

phosphorylation

down-regulates activity

0.515

We further show that Akt1 phosphorylates Skp2 at Ser72, which is required to disrupt the interaction between Cdh1 and Skp2.

SIGNOR-278274

Q16514

P17544

1

binding

up-regulates activity

0.515

We show that overexpression of hsTAF12 potentiates ATF7-induced transcriptional activation through direct interaction with ATF7, suggesting that TAF12 is a functional partner of ATF7.

SIGNOR-225249

O43525

O43526

2

binding

up-regulates activity

0.515

The M-current regulates the subthreshold electrical excitability of many neurons, determining their firing properties and responsiveness to synaptic input. To date, however, the genes that encode subunits of this important channel have not been identified. The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.

SIGNOR-268832

O43526

O43525

2

binding

up-regulates activity

0.515

The M-current regulates the subthreshold electrical excitability of many neurons, determining their firing properties and responsiveness to synaptic input. To date, however, the genes that encode subunits of this important channel have not been identified. The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current.

SIGNOR-268833

P21127

O00303

1

phosphorylation

up-regulates activity

0.515

EIF3f is phosphorylated by CDK11p46 at Ser46 during apoptosis.|Phosphorylation of eIF3f plays an important role in regulating its function in translation and apoptosis. Phosphorylation of eIF3f enhances the association of eIF3f with the core eIF3 subunits during apoptosis.

SIGNOR-273133

O60674

Q9UQC2

1

phosphorylation

up-regulates

0.515

In vitro, activated jak2 directly phosphorylated specific gab2 tyrosine residues. Mutagenesis studies revealed that gab2 tyrosine 643 (y643) was a major target of jak2 in vitro, and a key residue for jak2-dependent phosphorylation in intact cells. Mutation of gab2 y643 inhibited g-csf-stimulated erk1/2 activation and shp2 binding to gab2.

SIGNOR-179488

P49841

O75122

1

phosphorylation

down-regulates activity

0.515

GSK-3beta directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules.| CLASPs were originally identified as CLIP-170-interacting proteins and later found to be required for microtubule stabilisation at the cortical regions of epithelial cells

SIGNOR-264826

P24941

O43303

1

phosphorylation

down-regulates activity

0.515

GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)

SIGNOR-265956

O96017

P18887

1

phosphorylation

up-regulates

0.515

Chk2 formed a complex with xrcc1, the ber scaffold protein, and phosphorylated xrcc1 in vivo and in vitro at thr(284). our results are consistent with the phosphorylation of xrcc1 by atm-chk2 facilitating recruitment of downstream ber proteins to the initial damage recognition/excision step to promote ber.

SIGNOR-181816

P00519

P29323

1

phosphorylation

down-regulates

0.515

Two-hybrid screens identified regions of abl and arg that bind to the ephb2 and epha4 receptors, suggesting a novel signaling connection involving the two kinase families.The connection between EphB2 and Abl/Arg appears to be reciprocal. Activated EphB2 causes tyrosine phosphorylation of Abl and Arg, and vice versa. Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl.

SIGNOR-109668

Q05655

P04792

1

phosphorylation

down-regulates activity

0.515

Radioactive kinase assays confirmed that PKC\u03b4 phosphorylated Hsp27 at Ser78 and Ser82 ( Fig. 3 B).

SIGNOR-278425

Q9Y2H9

P60484

1

phosphorylation

down-regulates

0.515

Mast1 was found to associate to pten.

SIGNOR-138003

Q9ULT6

Q13467

1

ubiquitination

down-regulates quantity

0.515

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260118

O43318

Q15653

1

phosphorylation

down-regulates

0.515

Overexpression oftak1together with its activator protein,tak1binding protein 1 (tab1), induced thenucleartranslocation of nf-kappa b p50/p65 heterodimer accompanied by the degradation of i kappa b alpha and i kappa b beta, and the expression of kappa b-dependent reporter gene.

SIGNOR-55719

Q5S007

O95295

1

phosphorylation

down-regulates

0.514

Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2

SIGNOR-202436

Q14980

P68366

1

binding

up-regulates

0.514

Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules.

SIGNOR-116788

Q14157

P35226

1

binding

up-regulates activity

0.514

We identified UBAP2L as a novel BMI1-interacting protein. UBAP2L, BMI1, RNF2, and PHC1 define a novel Polycomb subcomplex

SIGNOR-261315

Q13501

P00441

1

binding

down-regulates quantity by destabilization

0.514

This study provides a novel molecular mechanism by which mutant SOD1 can be recognized by p62 in an ubiquitin-independent fashion and targeted for the autophagy-lysosome degradation pathway.

SIGNOR-262801

Q8IUQ4

Q9H2X6

1

polyubiquitination

down-regulates quantity by destabilization

0.514

Here we demonstrate that HIPK2 is an unstable protein that colocalizes and interacts with the E3 ubiquitin ligase Siah-1 in unstressed cells. Siah-1 knockdown increases HIPK2 stability and steady-state levels, whereas Siah-1 expression facilitates HIPK2 polyubiquitination, degradation and thereby inactivation.

SIGNOR-276166

P18146

P78337

1

binding

up-regulates activity

0.514

GNRH1 induces expression of early growth response 1 (EGR1), which interacts with steroidogenic factor 1 (SF1) and paired-like homeodomain transcription factor 1 (PITX1) to regulate Lhb promoter activity.

SIGNOR-254916

P31751

P16220

1

phosphorylation

up-regulates

0.514

Creb is a nuclear target for activation via the growth factor-dependent ser/thr kinase akt/pkb. When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp.

SIGNOR-62253

Q13627

P08151

1

phosphorylation

up-regulates activity

0.514

Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus .

SIGNOR-278930

P68400

P37840

1

phosphorylation

up-regulates

0.514

In vitro experiments and two-dimensional phosphopeptide mapping provided further evidence that serine 129 was phosphorylated by ck-1 and ck-2. Moreover, phosphorylation of serine 129 was reduced in vivo upon inhibition of ck-1 or ck-2. These data demonstrate that alpha-synuclein is constitutively phosphorylated within its c terminus and may indicate that the function of alpha-synuclein is regulated by phosphorylation/dephosphorylation.From these data we conclude that _-synuclein is predominantly phosphorylated at serine residue 129. However, a second serine at position 87 is also used for phosphorylation to some extent. together, these data may indicate that ck-1 and ck-2 are involved in the regulation of neuronal function and one may speculate that phosphorylation of _-synuclein could affect its binding to membranes.

SIGNOR-73807

P42336

Q06187

1

phosphorylation

up-regulates activity

0.514

Activation of Btk occurs by transphosphorylation of tyrosine 551 in the catalytic domain, resulting in a dramatic increase in the catalytic activity of the kinase (11, 12, 13). This allows for autophosphorylation at tyrosine 223 in the SH3 domain (14). Both Lyn and Syk have been demonstrated to be involved in BCR-mediated Btk activation (11), but processes that drive colocalization of these kinases are ill-defined. Recently, it was suggested that phosphatidylinositol 3-kinase (PI3-K) is also involved in Btk activation

SIGNOR-249610

P67775

Q9BUB5

1

dephosphorylation

down-regulates

0.514

Moreover, a dephosphorylation assay revealed that pp2a could directly dephosphorylate mnk1 and eif4e.

SIGNOR-168314

Q969G2

P28069

1

transcriptional regulation

up-regulates quantity by expression

0.514

We show that normal LHX4 binds to a human-specific element and subsequently activates transcription from the proximal upstream regulatory sequence of POUIF1, a gene encoding a POU homeodomain transcription factor known as the main regulator of GH expression.

SIGNOR-266056

Q8WZ64

P61586

1

gtpase-activating protein

down-regulates activity

0.514

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260453

P31749

P15976

1

phosphorylation

up-regulates

0.514

We found that akt directly phosphorylates the transcription factor gata-1 at serine 310 and that this site-specific phosphorylation is required for the transcriptional activation of the timp-1 promoter.

SIGNOR-139782

P35372

P08754

1

binding

up-regulates activity

0.513

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-256854

P00533

P37231

1

phosphorylation

down-regulates quantity by destabilization

0.513

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

SIGNOR-277190

P06493

Q96GX5

1

phosphorylation

up-regulates activity

0.513

We propose a model in which the initiating event for Gwl activation is phosphorylation by MPF of the proline-directed sites T193 and T206 in the presumptive activation loop

SIGNOR-249653

P12931

P35916

1

phosphorylation

up-regulates

0.513

Vegfr-3 is a direct c-src target and mass spectrometry analysis identified the sites phosphorylated by c-src as tyrosine 830, 833, 853, 1063, 1333, and 1337 vegfr-3 phosphorylation activates the recruitment to the receptor of the adaptor proteins crki/ii and shc inducing activation of jnk.

SIGNOR-165035

P28482

O60674

1

phosphorylation

down-regulates

0.513

We hypothesize that phosphorylation of ser523 in jak2 by erks 1 and/or 2 or other as-yet-unidentified kinases acts in a negative feedback manner

SIGNOR-236331

P28482

Q13362

2

phosphorylation

down-regulates

0.513

Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit.

SIGNOR-144313

Q13362

P28482

2

binding

down-regulates

0.513

B56-containing pp2a dephosphorylate erk and their activity is controlled by the early gene iex-1 and erk

SIGNOR-144325

P00519

P55211

1

phosphorylation

up-regulates

0.513

C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.

SIGNOR-133260

P78527

P00519

1

phosphorylation

up-regulates activity

0.513

We show that DNA-PK phosphorylates and activates c-Abl in vitro.

SIGNOR-279268

Q15418

O00418

1

phosphorylation

down-regulates activity

0.513

We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

SIGNOR-109708

P31751

Q86YS7

1

phosphorylation

up-regulates activity

0.513

MS analysis of an HA-CDP138 sample from the in vitro kinase assay revealed that active Akt2 induces CDP138 phosphorylation at serine (Ser)197, which lies within a consensus Akt substrate motif RQRLIS 197 ( xref ).

SIGNOR-279585

Q9UQM7

Q00613

1

phosphorylation

up-regulates activity

0.513

Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells.

SIGNOR-250631

P06493

P63279

1

phosphorylation

up-regulates activity

0.512

Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71.

SIGNOR-278174

Q13177

P35240

1

phosphorylation

down-regulates

0.512

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159768

Q9P107

P60953

1

gtpase-activating protein

down-regulates activity

0.512

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260507

Q8WWQ0

P35568

1

binding

up-regulates activity

0.512

We have recently reported the isolation of a PH domain-interacting protein, PHIP, which selectively binds to the IRS-1 PH domain and is stably associated with IRS-1 in mammalian cells. Here we demonstrate that overexpression of PHIP in fibroblasts enhances insulin-induced transcriptional responses in a mitogen-activated protein kinase-dependent manner.

SIGNOR-266962

Q92748

Q9NPA3

1

binding

down-regulates activity

0.512

In the current study, we have determined the crystal structure of mouse S14 to 2.65-Å resolution. The structure of S14 reveals a helical protein arranged as a symmetric dimer. Cultured cell experiments indicate that S14 can form heterodimers with MIG12, suggesting a mechanism through which S14 could modulate ACC activity and subsequently rates of fatty acid synthesis via heterodimer formation with MIG12.In the current study, we have shown that regulating the levels of S14∶MIG12 heterodimers regulates the ability of MIG12 to activate ACC. Increasing S14∶MIG12 heterodimers by the overexpression of S14 resulted in decreased ACC activity and polymerization, whereas decreasing S14∶MIG12 heterodimers by knockdown of S14 increased ACC activity and polymerization.

SIGNOR-267113

P15173

Q969P5

1

binding

down-regulates activity

0.512

Myogenin had a MAFbx-recognition motif and interacted with MAFbx. MAFbx activated polyubiquitination of myogenin. The results of this study suggest that MAFbx functions as an F-box protein for ubiquitination of myogenin.

SIGNOR-237854

P47871

P63092

1

binding

up-regulates activity

0.512

Glucagon signals through its receptor on the cell surface (Fig.1). The binding of glucagon to the extracellular loops of the glucagon receptor results in conformational changes of the latter, leading to subsequent activation of the coupled G proteins. At least two classes of G proteins are known to be associated with and involved in the signal transduction of the glucagon receptor, namely Gsα and Gq. The activation of Gsα leads to activation of adenylate cyclase, increase in intracellular cAMP levels, and subsequent activation of protein kinase A (PKA).

SIGNOR-267715

Q13315

Q13541

1

phosphorylation

down-regulates

0.512

Here we report that atm... phosphorylates 4e-bp1 at ser 111cells lacking atm kinase activity exhibit a significant decrease in the insulin-induced dissociation of 4e-bp1 from eif-4e.

SIGNOR-85619

Q13315

Q7LG56

1

phosphorylation

up-regulates

0.512

Atm-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53r2 protein against mdm2 to dna damage

SIGNOR-182423

P30556

P29992

1

binding

up-regulates activity

0.512

The angiotensin II type 1 receptor (AT1 R) is a G q/11-coupled G protein-coupled receptor that is widely expressed in multiple tissues, including vascular smooth muscle cells, brain, and kidney.

SIGNOR-278125

Q99996

Q15642

1

binding

up-regulates activity

0.512

Mechanistically, AKAP-9 interacted with cdc42 interacting protein 4 (CIP4) and regulated its expression. CIP4 levels were interrelated to the AKAP-9 level in CRC cells. Functionally, AKAP-9 was essential for TGF-β1-induced epithelial-mesenchymal transition of CRC cells, and CIP4 played a critical role in mediating the function of AKAP-9. Importantly, CIP4 expression was significantly up-regulated in human CRC tissues.|Co-immunoprecipitation assay revealed that AKAP-9 and CIP4 physically interacted with each other in Lovo and HT29 cells (Fig. 4B and C).

SIGNOR-260303

Q14012

P18846

1

phosphorylation

up-regulates activity

0.512

Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.

SIGNOR-250611

Q99986

P05412

1

phosphorylation

up-regulates

0.512

Vrk1 phosphorylates c-jun in ser63 and ser73 in vitro...VRK1 Activates c-jun dependent transcription

SIGNOR-127073

P17612

O14965

1

phosphorylation

up-regulates activity

0.512

Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.

SIGNOR-250337

Q9NQC7

P20749

1

deubiquitination

down-regulates

0.512

Cyld binds and deubiquitinates bcl-3in cyld+/+ keratinocytes, tpa or uv light triggers the translocation of cyld from the cytoplasm to the perinuclear region, where cyld binds and deubiquitinates bcl-3, thereby preventing nuclear accumulation of bcl-3 and p50/bcl-3- or p52/bcl-3-dependent proliferation.

SIGNOR-146774

P45983

P19419

1

phosphorylation

up-regulates activity

0.512

However, both of these stimuli strongly activate two other mapks, jnk1 and jnk2, and stimulate elk-1 transcriptional activity and phosphorylation jnk phosphorylation sites include ser383 and ser389, the major residues whose phosphorylation is responsible for enhancement of elk-1 trascriptional activity.

SIGNOR-236432

P22681

O94875

1

ubiquitination

down-regulates

0.512

Cbl-argbp2 complex mediates ubiquitination and degradation of c-abl

SIGNOR-96325

P15863

P50221

1

binding

up-regulates activity

0.512

We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.

SIGNOR-222193

Q06124

P32927

1

dephosphorylation

up-regulates

0.511

Shp2 is thought to act as a positive mediator of growth factor signals.. Hp2 could act as an adaptor between the activated c and grb2, thus leading to activation of the ras/mitogen-activated protein kinase pathway, known to be activated by il-3

SIGNOR-48557

Q16539

P04150

1

phosphorylation

up-regulates

0.511

We found serine 211 of the human gr to be a substrate for p38 mapk both in vitro and intracellularly. Mutation of this site to alanine greatly diminished gr-driven gene transcription and apoptosis.

SIGNOR-135198

Q96EB6

P23025

1

deacetylation

up-regulates activity

0.511

SIRT1 deacetylates XPA at residues K63, K67, and K215 to promote interactions with ATR

SIGNOR-262294

O15111

P42345

1

phosphorylation

up-regulates activity

0.511

In those studies, we found that IKKalpha interacts with and phosphorylates mTOR in the mTORC1 complex to activate mTORC1, and that Akt signaling drives the IKKalpha-mTORC1 interaction.|We then studied whether IKKalpha promotes Akt and mTOR activity in other mammalian cancer cell lines.

SIGNOR-279607

O43293

O14950

1

phosphorylation

up-regulates

0.511

Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.

SIGNOR-16043

P08754

O43306

1

binding

down-regulates activity

0.511

Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3

SIGNOR-278079

Q9HBE1

P78317

1

binding

down-regulates

0.511

In vitro and in vivo interaction between rnf4 and patz was demonstrated / patz acted as a transcriptional repressor, whereas its partner rnf4 behaved as a transcriptional activator./ the association of patz with rnf4 switches activation to repression

SIGNOR-75775

P28482

Q13485

1

phosphorylation

up-regulates

0.511

Phosphorylation of thr276 is shown to be important for tgf-?-Induced nuclear accumulation and, as a consequence, transcriptional activity of smad4. these results suggest that smad4 can be phosphorylated by erk2 at thr276.

SIGNOR-101660

P06493

Q12778

1

phosphorylation

down-regulates

0.511

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

SIGNOR-178202

O00230

Q96LB1

1

binding

up-regulates

0.511

The mrgx2 receptor has been shown to be activated by the peptides cortistatin and proadrenomedullin n-terminal peptides (pamp)

SIGNOR-139855