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
Q9HBW0	P63096	1	binding	up-regulates	0.625	Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.	SIGNOR-84559
Q13873	O00238	1	binding	up-regulates	0.625	Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors (br-ia and br-ib) and the bmp type ii receptor (br-ii).	SIGNOR-75655
Q92696	P20339	1	lipidation	up-regulates activity	0.625	Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional	SIGNOR-265572
Q16539	P03372	1	phosphorylation	up-regulates	0.625	Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells	SIGNOR-136950
P78357	Q12860	1	relocalization	up-regulates activity	0.625	These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.	SIGNOR-269073
Q9Y219	P46531	1	binding	up-regulates	0.625	Immunohistochemistry revealed coexpression of jagged2 and notch1 within thymus and other fetal murine tissues, consistent with interaction of the two proteins in vivo. Coculture of fibroblasts expressing human jagged2 with murine c2c12 myoblasts inhibited myogenic differentiation, accompanied by increased notch1 and the appearance of a novel 115-kda notch1 fragment. Exposure of c2c12 cells to jagged2 led to increased amounts of notch mrna as well as mrnas for a second notch receptor, notch3, and a second notch ligand, jagged1. Constitutively active forms of notchl in c2c12 cells also induced increased levels of the same set of mrnas, suggesting positive feedback control of these genes initiated by binding of jagged2 to notch1.	SIGNOR-236922
Q07820	Q16611	1	binding	down-regulates	0.625	Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax	SIGNOR-149774
O95390	Q13705	1	binding	up-regulates	0.625	Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2	SIGNOR-95309
Q9H1J7	O75581	1	binding	up-regulates	0.625	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131888
Q01484	Q9UJW0	1	relocalization	up-regulates quantity	0.625	We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.	SIGNOR-266713
P22694	P08138	1	phosphorylation	up-regulates	0.625	Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.	SIGNOR-99755
Q93098	Q9NPG1	1	binding	up-regulates	0.625	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-132024
Q92956	O00463	1	binding	up-regulates activity	0.625	ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5\|synergistic activation of NF-κB by ATAR and TRAF5 293 cells	SIGNOR-262592
P07948	Q9UN19	1	phosphorylation	up-regulates activity	0.625	Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines\|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.	SIGNOR-249378
Q9UN37	Q9Y3E7	1	cleavage	up-regulates activity	0.625	Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.	SIGNOR-260847
Q9Y219	Q9UM47	1	binding	up-regulates	0.625	These results suggest that delta1, jagged1, and jagged2 are ligands for notch1 and notch3 receptors.	SIGNOR-82401
O14640	P61586	1	binding	up-regulates activity	0.624	Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK)	SIGNOR-258971
P07949	Q9P104	1	binding	up-regulates	0.624	Dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase	SIGNOR-109516
P00747	P25116	1	cleavage	down-regulates activity	0.624	Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site.	SIGNOR-263572
P11802	Q08050	1	phosphorylation	up-regulates	0.624	We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence.	SIGNOR-177266
Q6PHR2	P53990	1	phosphorylation	down-regulates activity	0.624	ULK3 phosphorylation of IST1 is required to sustain the abscission checkpoint and inhibits IST1 function in abscission.	SIGNOR-278205
Q13464	O14950	1	phosphorylation	up-regulates	0.624	Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies.	SIGNOR-91542
A2RUS2	Q6IQ22	1	guanine nucleotide exchange factor	up-regulates activity	0.624	ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.\|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.	SIGNOR-264734
Q5S007	P37840	1	phosphorylation	down-regulates activity	0.624	Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD.	SIGNOR-249690
P12931	Q14289	1	phosphorylation	up-regulates	0.624	These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity.	SIGNOR-133870
P06493	Q99459	1	phosphorylation	up-regulates activity	0.624	Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.\|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression.	SIGNOR-279597
P24394	O60674	1	phosphorylation	up-regulates activity	0.624	Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.	SIGNOR-249530
P06401	P03372	1	binding	up-regulates	0.624	Here we identify two domains of prb, erid-i and -ii, mediating a direct interaction with the ligand-binding domain of eralpha.	SIGNOR-98807
P28482	P04150	1	phosphorylation	down-regulates activity	0.623	Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.\|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action.	SIGNOR-249428
Q13591	Q9ULL4	1	binding	up-regulates activity	0.623	Plexin-B3 is a functional receptor for semaphorin 5A. Here we show that plexin-B3 is a high-affinity receptor specific for Sema5A. We further demonstrate that plexin-B3 activation by Sema5A mediates functional responses in plexin-B3-expressing cells (either fibroblasts, epithelial and primary endothelial cells).	SIGNOR-268373
Q9GZT5	Q9NPG1	1	binding	up-regulates	0.623	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131616
P27361	P84022	1	phosphorylation	down-regulates	0.623	These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3.	SIGNOR-66781
P25490	P46531	1	binding	down-regulates activity	0.623	Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex [..] both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling.	SIGNOR-251654
P31751	P49841	1	phosphorylation	down-regulates activity	0.623	Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1	SIGNOR-245420
P13497	P20908	1	cleavage	up-regulates activity	0.623	BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595.	SIGNOR-256344
Q9NQ66	P29992	2	binding	up-regulates	0.623	Plc-_1 stimulates hydrolysis of gq/11-bound gtp and acts as a gtpase-activating protein (gap) for its physiologic regulator, gq/11	SIGNOR-17239
Q13535	Q9NVI1	1	phosphorylation	up-regulates activity	0.623	Alternatively, the locally accumulated ATRIP-ATR might have sufficient activity to phosphorylate FANCI without TOPBP1 stimulation.\|The results described above and our previous studies clearly indicated that FANCI phosphorylation is mediated by ATR kinase in a manner dependent on the FA core complex and FANCD2 protein.	SIGNOR-279320
O14905	Q9NPG1	1	binding	up-regulates	0.623	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-132111
Q15052	P63000	1	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
P49757	P08151	1	binding	down-regulates	0.623	The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation.	SIGNOR-167841
P35348	Q14344	1	binding	up-regulates activity	0.623	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-257279
Q13043	O95835	1	phosphorylation	up-regulates	0.623	We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.	SIGNOR-133551
Q9UBR4	P61371	1	binding	up-regulates activity	0.623	The Lhx3-Isl1 C terminus interaction was dependent on the LIM domains of Lhx3. The combinatorial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and Lhx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innervation targets, implying a functional role for LIM homeodomain protein combinations in the specification of neuronal identity	SIGNOR-220169
P06239	P27986	1	phosphorylation	down-regulates activity	0.623	the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.	SIGNOR-251383
O60674	P04626	1	phosphorylation	up-regulates activity	0.623	Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation.	SIGNOR-279197
P29992	Q9NQ66	2	binding	up-regulates activity	0.623	TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.	SIGNOR-267203
P29350	P21854	1	dephosphorylation	down-regulates	0.623	Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals.	SIGNOR-60155
Q05923	Q16539	1	dephosphorylation	down-regulates	0.623	We show that the in vivo substrate specificities of individual phosphatases are unique. Pac1, mkp-2, and mkp-1 recognize erk and p38, erk and jnk, and erk, p38, and jnk, respectively	SIGNOR-40918
P67775	P28749	1	dephosphorylation	up-regulates	0.623	Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.	SIGNOR-129749
Q16633	P14859	1	binding	up-regulates	0.622	Obf1 enhances transcriptional potential of oct1.	SIGNOR-100968
P35813	P84022	1	dephosphorylation	down-regulates activity	0.622	Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads.	SIGNOR-232110
Q16539	O95644	1	phosphorylation	down-regulates	0.622	We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.	SIGNOR-74560
P50750	P84022	1	phosphorylation	down-regulates activity	0.622	Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161589
Q00535	Q14194	1	phosphorylation	up-regulates	0.622	These findings suggest that sema3a-induced spine development is regulated by phosphorylation of crmp1 by cdk5. Introduction of crmp1-wt, but not crmp1-t509a/s522a, a crmp1 mutant that cannot be phosphorylated by cdk5, rescued the defect in sema3a responsiveness.	SIGNOR-159314
Q9BWP8	P48740	1	binding	up-regulates activity	0.622	On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.	SIGNOR-263409
P17706	P06213	1	dephosphorylation	down-regulates	0.622	Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1.	SIGNOR-75914
P53350	O75122	1	phosphorylation	up-regulates activity	0.622	Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments.\|Finally, we demonstrate that CLASP2 phosphorylation on S1234 and S1255 by Cdk1 and Plk1, respectively, increases with conditions that allow the establishment and stabilization of KT\u2013MT attachments ( xref ).	SIGNOR-278321
P31749	P84022	1	binding	down-regulates	0.622	Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis.	SIGNOR-123606
P02545	Q9UH99	1	relocalization	up-regulates activity	0.622	In the case of Sun2, there is some evidence that A-type lamins might contribute to Sun2 localization in the INM. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.	SIGNOR-261310
Q13882	P40763	1	phosphorylation	up-regulates activity	0.622	29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.\|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer.	SIGNOR-278346
Q86VW2	P63000	1	guanine nucleotide exchange factor	up-regulates	0.622	Exogenous expression of geft promotes myogenesis ofc2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process.	SIGNOR-236882
Q12972	P62136	1	binding	down-regulates activity	0.622	We have purified two of these nuclear inhibitors of PP-1 (NIPP-1a and NIPP-1b) until homogeneity.	SIGNOR-255657
P40763	P14210	1	transcriptional regulation	up-regulates quantity by expression	0.622	Coexpression of activated c-Src and Stat3 synergistically induced strong HGF promoter activity in SP1 cells	SIGNOR-251742
O14904	Q9NPG1	1	binding	up-regulates	0.622	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-132070
Q15831	P43268	1	phosphorylation	down-regulates quantity by destabilization	0.622	LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism.	SIGNOR-279293
Q06124	P21802	1	dephosphorylation	down-regulates activity	0.622	In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).\|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2.	SIGNOR-277030
Q2M1P5	P08151	1	binding	up-regulates quantity by stabilization	0.622	Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling.	SIGNOR-209608
P67775	P28482	1	dephosphorylation	down-regulates activity	0.621	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).Mapk activity is tightly regulated by phosphorylation and dephosphorylation. The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase	SIGNOR-103159
O60346	P31751	1	dephosphorylation	down-regulates activity	0.621	The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.\|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.	SIGNOR-248328
Q00987	Q92831	1	ubiquitination	down-regulates quantity by destabilization	0.621	Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.\|MDM2 ubiquitinated PCAF in vitro and in cells.	SIGNOR-278825
O14492	P06213	1	binding	down-regulates	0.621	APS couples c-Cbl to the insulin receptor, resulting in ubiquitination of the insulin receptor.	SIGNOR-109694
Q53G59	O14640	1	binding	down-regulates quantity by destabilization	0.621	KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation.	SIGNOR-271558
Q16539	P40763	1	phosphorylation	up-regulates	0.621	All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).	SIGNOR-154783
P45983	O95644	1	phosphorylation	down-regulates activity	0.621	It has been previously shown that NF-ATc1 accumulates in the nucleus of activated CD4 + T cells from Jnk1 \n \u2212/\u2212 mice 35\u2022 and that JNK1 phosphorylates and inactivates NFATc1 in Jurkat T cells 47 , indicating that JNK1 is an inhibitor of NFAT.	SIGNOR-280031
P13945	P63092	1	binding	up-regulates activity	0.621	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-256753
O14640	P49841	1	binding	down-regulates activity	0.621	In canonical wnt signaling, dsh phosphorylation inhibits the apcaxingsk3 complex, leading to beta-catenin stabilization.	SIGNOR-167957
Q96EB6	O75376	1	null	up-regulates	0.621	In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.	SIGNOR-253505
Q96EB6	P15172	1	null	down-regulates activity	0.621	Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation	SIGNOR-241963
Q9H1J5	Q9NPG1	1	binding	up-regulates	0.621	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131984
Q6PHR2	P10070	1	phosphorylation	up-regulates activity	0.621	We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro	SIGNOR-260798
O75582	P05114	1	phosphorylation	down-regulates activity	0.62	HMGN1 (formerly known as HMG-14) phosphorylation at Ser6 occurs concomitantly with IE gene expression. \| MSK2 seems to be the most important kinase responsible for this modification \|Accordingly, it was suggested that HMGN1 phosphorylation reduces binding of the protein to the nucleosomes	SIGNOR-262988
P51878	P57764	1	cleavage	up-regulates activity	0.62	Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD\|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence \|	SIGNOR-256418
Q9NPE3	O14746	1	binding	up-regulates activity	0.62	Dyskerin was recently found to be associated with active human telomerase (34), and mutations in dyskerin or NOP10 or deletion of the H/ACA motif of hTERC result in diminished telomerase activity	SIGNOR-263331
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
P15976	P17947	2	binding	down-regulates activity	0.62	GATA-1 represses PU.1 activity.We have in this report found that the GATA-1 transcription factor is capable of functionally interfering with the PU.1 protein and have provided evidence that this interference is mediated through interaction between the PU.1 ETS domain and the GATA-1 C-finger region.	SIGNOR-256050
Q16566	P56524	1	phosphorylation	down-regulates activity	0.62	CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. \| Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. \| Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.	SIGNOR-250712
P02649	Q92673	1	binding	up-regulates	0.62	Lr11 binds the apolipoprotein e (apoe)-rich lipoproteins, beta-very low density lipoproteins (vldls), with a high affinity similar to that of other members, such as the ldlr and vldl receptor.Incubation For 48 hours with beta-vldl of lr11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets.	SIGNOR-110555
Q70Z35	P60484	2	binding	down-regulates activity	0.62	Here, we report that P-REX2 interacts with PTEN via two interfaces. In summary, P-REX2 docks to the PDZ-BD of PTEN through its C-terminal domain, reads the phosphorylation state of the PTEN tail via the DH domain, and inhibits PTEN activity by unleashing the PH domain	SIGNOR-259189
P68400	Q13547	1	phosphorylation	up-regulates	0.62	Human hdac1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, ser(421) and ser(423), were unambiguously identified. Loss of phosphorylation at ser(421) and ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of hdac1.	SIGNOR-111015
P49137	Q07352	1	phosphorylation	down-regulates	0.62	Mk2-mediated inhibition of brf1 requires phosphorylation at s54, s92, and s203. Phosphorylation of brf1 by mk2 does not appear to alter its ability to interact with ares or to associate with mrna decay enzymes. Thus, mk2 inhibits brf1-dependent amd through direct phosphorylation.	SIGNOR-161274
P31269	O00470	1	binding	up-regulates activity	0.62	We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.	SIGNOR-241162
Q16661	P25092	1	binding	up-regulates	0.62	Guanylins activate two receptors, gc-c and ok-gc, which are expressed in intestine and/or kidney.	SIGNOR-78120
Q9Y6E7	P00367	1	glycosylation	down-regulates activity	0.62	We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity.	SIGNOR-267828
Q8N5S9	Q16566	1	phosphorylation	up-regulates	0.62	Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity.	SIGNOR-134649
Q13188	O95835	1	phosphorylation	up-regulates	0.62	Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1.	SIGNOR-132927
Q96RR4	Q16566	1	phosphorylation	up-regulates activity	0.62	Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation.	SIGNOR-250718
P07948	P16885	1	phosphorylation	up-regulates activity	0.62	The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.	SIGNOR-249384
O14920	Q04864	1	phosphorylation	up-regulates activity	0.62	We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.	SIGNOR-279620
P18146	P37231	1	transcriptional regulation	down-regulates quantity by repression	0.62	Previous studies have reported that the PPARγ proximal promoter contains an overlapping binding site for Egr-1, which is involved in the down-regulation of PPARγ. In the present study, we have provided direct evidence that leptin causes PPARγ reduction in primary cultured PASMC; this effect is coupled to leptin-induced ERK1/2 activation and subsequent induction of Egr-1, which further down-regulates PPARγ expression and results in PASMC proliferation. The present study confirmed that ERK1/2 signaling cascade mediated leptin-induced PPARγ reduction by up-regulation of Egr-1 in PASMC.	SIGNOR-263508
P17947	P15976	2	binding	down-regulates activity	0.62	We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation.	SIGNOR-256049

Q9HBW0

P63096

1

binding

up-regulates

0.625

Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies.

SIGNOR-84559

Q13873

O00238

1

binding

up-regulates

0.625

Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors (br-ia and br-ib) and the bmp type ii receptor (br-ii).

SIGNOR-75655

Q92696

P20339

1

lipidation

up-regulates activity

0.625

Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional

SIGNOR-265572

Q16539

P03372

1

phosphorylation

up-regulates

0.625

Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells

SIGNOR-136950

P78357

Q12860

1

relocalization

up-regulates activity

0.625

These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.

SIGNOR-269073

Q9Y219

P46531

1

binding

up-regulates

0.625

Immunohistochemistry revealed coexpression of jagged2 and notch1 within thymus and other fetal murine tissues, consistent with interaction of the two proteins in vivo. Coculture of fibroblasts expressing human jagged2 with murine c2c12 myoblasts inhibited myogenic differentiation, accompanied by increased notch1 and the appearance of a novel 115-kda notch1 fragment. Exposure of c2c12 cells to jagged2 led to increased amounts of notch mrna as well as mrnas for a second notch receptor, notch3, and a second notch ligand, jagged1. Constitutively active forms of notchl in c2c12 cells also induced increased levels of the same set of mrnas, suggesting positive feedback control of these genes initiated by binding of jagged2 to notch1.

SIGNOR-236922

Q07820

Q16611

1

binding

down-regulates

0.625

Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax

SIGNOR-149774

O95390

Q13705

1

binding

up-regulates

0.625

Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2

SIGNOR-95309

Q9H1J7

O75581

1

binding

up-regulates

0.625

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131888

Q01484

Q9UJW0

1

relocalization

up-regulates quantity

0.625

We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4.

SIGNOR-266713

P22694

P08138

1

phosphorylation

up-regulates

0.625

Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth.

SIGNOR-99755

Q93098

Q9NPG1

1

binding

up-regulates

0.625

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-132024

Q92956

O00463

1

binding

up-regulates activity

0.625

ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5|synergistic activation of NF-κB by ATAR and TRAF5 293 cells

SIGNOR-262592

P07948

Q9UN19

1

phosphorylation

up-regulates activity

0.625

Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins.

SIGNOR-249378

Q9UN37

Q9Y3E7

1

cleavage

up-regulates activity

0.625

Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission.

SIGNOR-260847

Q9Y219

Q9UM47

1

binding

up-regulates

0.625

These results suggest that delta1, jagged1, and jagged2 are ligands for notch1 and notch3 receptors.

SIGNOR-82401

O14640

P61586

1

binding

up-regulates activity

0.624

Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK)

SIGNOR-258971

P07949

Q9P104

1

binding

up-regulates

0.624

Dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase

SIGNOR-109516

P00747

P25116

1

cleavage

down-regulates activity

0.624

Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site.

SIGNOR-263572

P11802

Q08050

1

phosphorylation

up-regulates

0.624

We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence.

SIGNOR-177266

Q6PHR2

P53990

1

phosphorylation

down-regulates activity

0.624

ULK3 phosphorylation of IST1 is required to sustain the abscission checkpoint and inhibits IST1 function in abscission.

SIGNOR-278205

Q13464

O14950

1

phosphorylation

up-regulates

0.624

Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies.

SIGNOR-91542

A2RUS2

Q6IQ22

1

guanine nucleotide exchange factor

up-regulates activity

0.624

ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy.

SIGNOR-264734

Q5S007

P37840

1

phosphorylation

down-regulates activity

0.624

Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD.

SIGNOR-249690

P12931

Q14289

1

phosphorylation

up-regulates

0.624

These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity.

SIGNOR-133870

P06493

Q99459

1

phosphorylation

up-regulates activity

0.624

Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression.

SIGNOR-279597

P24394

O60674

1

phosphorylation

up-regulates activity

0.624

Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.

SIGNOR-249530

P06401

P03372

1

binding

up-regulates

0.624

Here we identify two domains of prb, erid-i and -ii, mediating a direct interaction with the ligand-binding domain of eralpha.

SIGNOR-98807

P28482

P04150

1

phosphorylation

down-regulates activity

0.623

Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action.

SIGNOR-249428

Q13591

Q9ULL4

1

binding

up-regulates activity

0.623

Plexin-B3 is a functional receptor for semaphorin 5A. Here we show that plexin-B3 is a high-affinity receptor specific for Sema5A. We further demonstrate that plexin-B3 activation by Sema5A mediates functional responses in plexin-B3-expressing cells (either fibroblasts, epithelial and primary endothelial cells).

SIGNOR-268373

Q9GZT5

Q9NPG1

1

binding

up-regulates

0.623

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131616

P27361

P84022

1

phosphorylation

down-regulates

0.623

These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3.

SIGNOR-66781

P25490

P46531

1

binding

down-regulates activity

0.623

Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex [..] both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling.

SIGNOR-251654

P31751

P49841

1

phosphorylation

down-regulates activity

0.623

Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1

SIGNOR-245420

P13497

P20908

1

cleavage

up-regulates activity

0.623

BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595.

SIGNOR-256344

Q9NQ66

P29992

2

binding

up-regulates

0.623

Plc-_1 stimulates hydrolysis of gq/11-bound gtp and acts as a gtpase-activating protein (gap) for its physiologic regulator, gq/11

SIGNOR-17239

Q13535

Q9NVI1

1

phosphorylation

up-regulates activity

0.623

Alternatively, the locally accumulated ATRIP-ATR might have sufficient activity to phosphorylate FANCI without TOPBP1 stimulation.|The results described above and our previous studies clearly indicated that FANCI phosphorylation is mediated by ATR kinase in a manner dependent on the FA core complex and FANCD2 protein.

SIGNOR-279320

O14905

Q9NPG1

1

binding

up-regulates

0.623

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-132111

Q15052

P63000

1

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

P49757

P08151

1

binding

down-regulates

0.623

The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation.

SIGNOR-167841

P35348

Q14344

1

binding

up-regulates activity

0.623

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-257279

Q13043

O95835

1

phosphorylation

up-regulates

0.623

We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity.

SIGNOR-133551

Q9UBR4

P61371

1

binding

up-regulates activity

0.623

The Lhx3-Isl1 C terminus interaction was dependent on the LIM domains of Lhx3. The combinatorial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and Lhx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innervation targets, implying a functional role for LIM homeodomain protein combinations in the specification of neuronal identity

SIGNOR-220169

P06239

P27986

1

phosphorylation

down-regulates activity

0.623

the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.

SIGNOR-251383

O60674

P04626

1

phosphorylation

up-regulates activity

0.623

Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation.

SIGNOR-279197

P29992

Q9NQ66

2

binding

up-regulates activity

0.623

TRH-R1 receptor, which is coupled to Gq/11 protein, activates phospholipase C, mobilizes calcium and activates protein kinase C.

SIGNOR-267203

P29350

P21854

1

dephosphorylation

down-regulates

0.623

Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals.

SIGNOR-60155

Q05923

Q16539

1

dephosphorylation

down-regulates

0.623

We show that the in vivo substrate specificities of individual phosphatases are unique. Pac1, mkp-2, and mkp-1 recognize erk and p38, erk and jnk, and erk, p38, and jnk, respectively

SIGNOR-40918

P67775

P28749

1

dephosphorylation

up-regulates

0.623

Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation.

SIGNOR-129749

Q16633

P14859

1

binding

up-regulates

0.622

Obf1 enhances transcriptional potential of oct1.

SIGNOR-100968

P35813

P84022

1

dephosphorylation

down-regulates activity

0.622

Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads.

SIGNOR-232110

Q16539

O95644

1

phosphorylation

down-regulates

0.622

We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats.

SIGNOR-74560

P50750

P84022

1

phosphorylation

down-regulates activity

0.622

Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161589

Q00535

Q14194

1

phosphorylation

up-regulates

0.622

These findings suggest that sema3a-induced spine development is regulated by phosphorylation of crmp1 by cdk5. Introduction of crmp1-wt, but not crmp1-t509a/s522a, a crmp1 mutant that cannot be phosphorylated by cdk5, rescued the defect in sema3a responsiveness.

SIGNOR-159314

Q9BWP8

P48740

1

binding

up-regulates activity

0.622

On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.

SIGNOR-263409

P17706

P06213

1

dephosphorylation

down-regulates

0.622

Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1.

SIGNOR-75914

P53350

O75122

1

phosphorylation

up-regulates activity

0.622

Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments.|Finally, we demonstrate that CLASP2 phosphorylation on S1234 and S1255 by Cdk1 and Plk1, respectively, increases with conditions that allow the establishment and stabilization of KT\u2013MT attachments ( xref ).

SIGNOR-278321

P31749

P84022

1

binding

down-regulates

0.622

Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis.

SIGNOR-123606

P02545

Q9UH99

1

relocalization

up-regulates activity

0.622

In the case of Sun2, there is some evidence that A-type lamins might contribute to Sun2 localization in the INM. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation.

SIGNOR-261310

Q13882

P40763

1

phosphorylation

up-regulates activity

0.622

29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer.

SIGNOR-278346

Q86VW2

P63000

1

guanine nucleotide exchange factor

up-regulates

0.622

Exogenous expression of geft promotes myogenesis ofc2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process.

SIGNOR-236882

Q12972

P62136

1

binding

down-regulates activity

0.622

We have purified two of these nuclear inhibitors of PP-1 (NIPP-1a and NIPP-1b) until homogeneity.

SIGNOR-255657

P40763

P14210

1

transcriptional regulation

up-regulates quantity by expression

0.622

Coexpression of activated c-Src and Stat3 synergistically induced strong HGF promoter activity in SP1 cells

SIGNOR-251742

O14904

Q9NPG1

1

binding

up-regulates

0.622

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-132070

Q15831

P43268

1

phosphorylation

down-regulates quantity by destabilization

0.622

LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism.

SIGNOR-279293

Q06124

P21802

1

dephosphorylation

down-regulates activity

0.622

In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2.

SIGNOR-277030

Q2M1P5

P08151

1

binding

up-regulates quantity by stabilization

0.622

Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling.

SIGNOR-209608

P67775

P28482

1

dephosphorylation

down-regulates activity

0.621

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).Mapk activity is tightly regulated by phosphorylation and dephosphorylation. The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase

SIGNOR-103159

O60346

P31751

1

dephosphorylation

down-regulates activity

0.621

The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.

SIGNOR-248328

Q00987

Q92831

1

ubiquitination

down-regulates quantity by destabilization

0.621

Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells.

SIGNOR-278825

O14492

P06213

1

binding

down-regulates

0.621

APS couples c-Cbl to the insulin receptor, resulting in ubiquitination of the insulin receptor.

SIGNOR-109694

Q53G59

O14640

1

binding

down-regulates quantity by destabilization

0.621

KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation.

SIGNOR-271558

Q16539

P40763

1

phosphorylation

up-regulates

0.621

All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below).

SIGNOR-154783

P45983

O95644

1

phosphorylation

down-regulates activity

0.621

It has been previously shown that NF-ATc1 accumulates in the nucleus of activated CD4 + T cells from Jnk1 \n \u2212/\u2212 mice 35\u2022 and that JNK1 phosphorylates and inactivates NFATc1 in Jurkat T cells 47 , indicating that JNK1 is an inhibitor of NFAT.

SIGNOR-280031

P13945

P63092

1

binding

up-regulates activity

0.621

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-256753

O14640

P49841

1

binding

down-regulates activity

0.621

In canonical wnt signaling, dsh phosphorylation inhibits the apcaxingsk3 complex, leading to beta-catenin stabilization.

SIGNOR-167957

Q96EB6

O75376

1

null

up-regulates

0.621

In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.

SIGNOR-253505

Q96EB6

P15172

1

null

down-regulates activity

0.621

Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation

SIGNOR-241963

Q9H1J5

Q9NPG1

1

binding

up-regulates

0.621

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131984

Q6PHR2

P10070

1

phosphorylation

up-regulates activity

0.621

We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro

SIGNOR-260798

O75582

P05114

1

phosphorylation

down-regulates activity

0.62

HMGN1 (formerly known as HMG-14) phosphorylation at Ser6 occurs concomitantly with IE gene expression. | MSK2 seems to be the most important kinase responsible for this modification |Accordingly, it was suggested that HMGN1 phosphorylation reduces binding of the protein to the nucleosomes

SIGNOR-262988

P51878

P57764

1

cleavage

up-regulates activity

0.62

Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence |

SIGNOR-256418

Q9NPE3

O14746

1

binding

up-regulates activity

0.62

Dyskerin was recently found to be associated with active human telomerase (34), and mutations in dyskerin or NOP10 or deletion of the H/ACA motif of hTERC result in diminished telomerase activity

SIGNOR-263331

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

P15976

P17947

2

binding

down-regulates activity

0.62

GATA-1 represses PU.1 activity.We have in this report found that the GATA-1 transcription factor is capable of functionally interfering with the PU.1 protein and have provided evidence that this interference is mediated through interaction between the PU.1 ETS domain and the GATA-1 C-finger region.

SIGNOR-256050

Q16566

P56524

1

phosphorylation

down-regulates activity

0.62

CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.

SIGNOR-250712

P02649

Q92673

1

binding

up-regulates

0.62

Lr11 binds the apolipoprotein e (apoe)-rich lipoproteins, beta-very low density lipoproteins (vldls), with a high affinity similar to that of other members, such as the ldlr and vldl receptor.Incubation For 48 hours with beta-vldl of lr11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets.

SIGNOR-110555

Q70Z35

P60484

2

binding

down-regulates activity

0.62

Here, we report that P-REX2 interacts with PTEN via two interfaces. In summary, P-REX2 docks to the PDZ-BD of PTEN through its C-terminal domain, reads the phosphorylation state of the PTEN tail via the DH domain, and inhibits PTEN activity by unleashing the PH domain

SIGNOR-259189

P68400

Q13547

1

phosphorylation

up-regulates

0.62

Human hdac1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, ser(421) and ser(423), were unambiguously identified. Loss of phosphorylation at ser(421) and ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of hdac1.

SIGNOR-111015

P49137

Q07352

1

phosphorylation

down-regulates

0.62

Mk2-mediated inhibition of brf1 requires phosphorylation at s54, s92, and s203. Phosphorylation of brf1 by mk2 does not appear to alter its ability to interact with ares or to associate with mrna decay enzymes. Thus, mk2 inhibits brf1-dependent amd through direct phosphorylation.

SIGNOR-161274

P31269

O00470

1

binding

up-regulates activity

0.62

We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets.

SIGNOR-241162

Q16661

P25092

1

binding

up-regulates

0.62

Guanylins activate two receptors, gc-c and ok-gc, which are expressed in intestine and/or kidney.

SIGNOR-78120

Q9Y6E7

P00367

1

glycosylation

down-regulates activity

0.62

We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity.

SIGNOR-267828

Q8N5S9

Q16566

1

phosphorylation

up-regulates

0.62

Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity.

SIGNOR-134649

Q13188

O95835

1

phosphorylation

up-regulates

0.62

Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1.

SIGNOR-132927

Q96RR4

Q16566

1

phosphorylation

up-regulates activity

0.62

Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation.

SIGNOR-250718

P07948

P16885

1

phosphorylation

up-regulates activity

0.62

The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors.

SIGNOR-249384

O14920

Q04864

1

phosphorylation

up-regulates activity

0.62

We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.

SIGNOR-279620

P18146

P37231

1

transcriptional regulation

down-regulates quantity by repression

0.62

Previous studies have reported that the PPARγ proximal promoter contains an overlapping binding site for Egr-1, which is involved in the down-regulation of PPARγ. In the present study, we have provided direct evidence that leptin causes PPARγ reduction in primary cultured PASMC; this effect is coupled to leptin-induced ERK1/2 activation and subsequent induction of Egr-1, which further down-regulates PPARγ expression and results in PASMC proliferation. The present study confirmed that ERK1/2 signaling cascade mediated leptin-induced PPARγ reduction by up-regulation of Egr-1 in PASMC.

SIGNOR-263508

P17947

P15976

2

binding

down-regulates activity

0.62

We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation.

SIGNOR-256049