GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P47736	Q9Y297	ubiquitination	down-regulates	0.342	Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex.	SIGNOR-203548
P54274	Q8TDX7	phosphorylation	up-regulates activity	0.342	Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.\|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres.	SIGNOR-278447
P09884	P09874	binding	up-regulates activity	0.342	We provide evidence that in proliferating cells: (i) PARP is physically associated with the catalytic subunit of the DNA polymerase α–primase tetramer, an association confirmed by confocal microscopy, demonstrating that both enzymes are co-localized at the nuclear periphery of HeLa cells.\|(iii) PARP-deficient cells derived from PARP knock-out mice exhibited reduced DNA polymerase activity,	SIGNOR-261270
P08263	Q16236	transcriptional regulation	up-regulates quantity by expression	0.342	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256278
Q7Z3C6	P12931	phosphorylation	up-regulates activity	0.342	Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.	SIGNOR-266367
P26358	P24941	phosphorylation	up-regulates	0.342	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173681
P49840	Q05655	phosphorylation	down-regulates	0.342	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115722
P15311	Q15475	transcriptional regulation	up-regulates quantity	0.342	We now show that the gene encoding Ezrin is a direct transcriptional target of Six1.	SIGNOR-259374
P31939	P50552	phosphorylation	up-regulates activity	0.342	ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity.	SIGNOR-276172
Q14765	P52564	phosphorylation	up-regulates activity	0.342	MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity.	SIGNOR-251425
P15311	P41743	phosphorylation	up-regulates	0.342	Pkciota phosphorylated ezrin on t567 in vitro, and in sf9 cells that do not activate human ezrin. we conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by pkciota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.	SIGNOR-160855
P50148	Q96LB2	binding	up-regulates activity	0.342	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-257384
Q02535	P24941	phosphorylation	down-regulates	0.342	We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._	SIGNOR-53306
Q9UQB8	Q14678	binding	down-regulates activity	0.342	In this study, we report that Kank disrupts the function of active Rac1 through IRSp53. The binding between IRSp53 and Kank inhibits the association of active Rac1 with IRSp53 rather than the association of active cdc42 with IRSp53. Kank inhibits the formation of lamellipodia and membrane ruffles induced by active Rac1 in NIH3T3 cells. Kank interacts with IRSp53 through their coiled-coil domains. Kank affected the interaction between IRSp53 and Rac1 and partially affected that between IRSp53 and cdc42 (Fig. 3).	SIGNOR-265553
O15105	O15379	binding	up-regulates	0.342	We show here that smad7 can form a complex with endogenous histone deacetylase proteins hdac-1 and hdac-3 in nih 3t3 mouse fibroblast cells	SIGNOR-199967
P49768	P55210	cleavage	up-regulates activity	0.342	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261757
Q9H867	Q9BZE9	binding	up-regulates	0.342	In the case of vcp, methylation by mettl21d was stimulated by the addition of the ubx cofactor aspscr1, which we show directly interacts with the methyltransferase.	SIGNOR-200572
P10163	Q96L73	transcriptional regulation	up-regulates quantity by expression	0.342	We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter.	SIGNOR-268459
P31749	P10586	dephosphorylation	down-regulates	0.342	Knock-down of lar by the l3 sirna probe markedly inhibited the insulin-stimulated increase in the phosphorylation of protein kinase b (pkb, also called akt) on serine 473 by >90%	SIGNOR-137246
Q00987	O43293	phosphorylation	up-regulates quantity by stabilization	0.342	Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein.	SIGNOR-123159
O00308	Q07912	phosphorylation	up-regulates activity	0.342	ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.\|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1.	SIGNOR-279302
Q7KZF4	Q12772	transcriptional regulation	up-regulates quantity by expression	0.342	These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.	SIGNOR-259136
P98164	P08253	binding	up-regulates quantity	0.342	We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells.	SIGNOR-265255
P53602	P38646	binding	down-regulates activity	0.342	Mortalin binds to mevalonate pyrophosphate decarboxyl ase in mammalian cell. Mot-2 inactivates MPD resulting in decreased amounts of the steady state Ras protein.	SIGNOR-265890
P25963	Q9UN86	relocalization	down-regulates activity	0.342	IkappaBalpha interacts with G3BP2 both in vivo and in vitrothrough the IkappaBalpha CRS. Overexpression of G3BP2 directly promotes retention of IkappaBalpha in the cytoplasm.	SIGNOR-260985
P04183	Q9UM11	binding	down-regulates quantity by destabilization	0.342	We show that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a necessary but also a rate-limiting factor for mitotic degradation of hTK1. By in vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif.	SIGNOR-272945
Q9Y2Y9	Q13523	phosphorylation	down-regulates	0.342	Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription.	SIGNOR-154951
P08588	Q9HD26	relocalization	down-regulates	0.342	Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell	SIGNOR-128791
Q8N6P7	Q6X9E4	binding	down-regulates quantity by destabilization	0.342	FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro.	SIGNOR-272426
O00327	P11387	transcriptional regulation	down-regulates quantity by repression	0.342	We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition.	SIGNOR-277354
P33076	P27361	phosphorylation	up-regulates	0.341	We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.	SIGNOR-150545
Q09472	Q9UK99	binding	down-regulates quantity by destabilization	0.341	O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway.	SIGNOR-271742
Q9H9S0	Q9HCS4	transcriptional regulation	down-regulates quantity by repression	0.341	These experiments showed that Tcf3 is associated with chromatin in the Nanog promoter regions and that the DNA-binding activity of Tcf3 was required for repression.	SIGNOR-266081
Q13541	P68400	phosphorylation	down-regulates	0.341	Phosphorylation at s112 directly affects binding of 4e-bp1 to eif4e without influencing phosphorylation of other sites.	SIGNOR-98280
Q01196	P06493	phosphorylation	up-regulates	0.341	Phosphorylation of runx1 on ser-303 by cdks leads its ubiquitin-mediated degradation during g2/m (19). We developed additional evidence that cdks phosphorylate ser-303 and found that ser-48 and ser-424 are also substrates of cdk1/cyclin b and cdk6/cyclin d3. Moreover, we demonstrated that phosphorylation of ser-48, ser-303, and ser-424 strengthens the ability of runx1 to activate transcription and to stimulate proliferation of the ba/f3 hematopoietic cell line (20).	SIGNOR-169322
O15516	P49841	phosphorylation	down-regulates quantity by destabilization	0.341	We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427.	SIGNOR-276270
Q9Y5X2	P23458	phosphorylation	up-regulates activity	0.341	IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.	SIGNOR-273647
Q9NR28	P53779	phosphorylation	down-regulates	0.341	Here we demonstrate that jnk3 can phosphorylate smac. Phosphorylation of smac by jnk3 attenuates its interaction with xiap. These results suggest that jnk3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between smac and xiap.	SIGNOR-157280
Q9UQL6	Q13131	phosphorylation	down-regulates	0.341	Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)	SIGNOR-176479
Q8TAP9	P06493	phosphorylation	up-regulates	0.341	Ttdn1 is phosphorylated by cdk1 in vitro and in vivo. Ttdn1 is phosphorylated at multiple residues, including ser93 and ser104. Mutation of thr120 of ttdn1 abolishes its interaction with plk1, suggesting phosphorylation of thr120 in the consensus plk1-binding motif is required for its interaction with plk1	SIGNOR-153308
Q02363	Q9Y574	polyubiquitination	down-regulates quantity by destabilization	0.341	Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion.	SIGNOR-272053
P12004	P00533	phosphorylation	up-regulates	0.341	Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions.	SIGNOR-150852
Q13443	P50281	cleavage	down-regulates quantity by destabilization	0.341	Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9\|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).	SIGNOR-260301
P07355	Q5T6F2	ubiquitination	down-regulates quantity	0.341	UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination	SIGNOR-261314
Q01130	P61011	binding	up-regulates activity	0.341	We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65).	SIGNOR-261160
O15350	P46777	binding	up-regulates	0.341	We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73	SIGNOR-205517
Q04206	Q9H000	ubiquitination	down-regulates quantity by destabilization	0.341	MKRN2 promotes p65 ubiquitination and degradation through RING finger domain.	SIGNOR-278591
P19544	P17612	phosphorylation	down-regulates	0.341	Pka phosphorylated wt1 at ser-365 and ser-393 in vitro, as well as at additional sites, and this phosphorylation abolished the dna-binding activity of wt1 in vitro. Using wt1 mutants in which ser-365 and ser-393 were mutated to ala individually and in combination, we showed that phosphorylation of these sites was critical for inhibition of dna binding in vivo.	SIGNOR-53172
P23443	Q13362	binding	down-regulates	0.341	The human homolog of pp2a-b', ppp2r5c, also counteracts s6k1 phosphorylation, indicating a conserved mechanism in mammals	SIGNOR-165224
P21860	Q00535	phosphorylation	up-regulates activity	0.341	We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival.	SIGNOR-250663
Q92974	Q9ULJ8	binding	up-regulates activity	0.341	The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc	SIGNOR-269177
Q05682	Q00535	phosphorylation	down-regulates quantity by destabilization	0.341	Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.	SIGNOR-280215
P06127	P05129	phosphorylation	up-regulates	0.341	Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.	SIGNOR-85183
Q6WKZ4	Q7KZI7	phosphorylation	up-regulates quantity	0.341	We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.	SIGNOR-273676
P05771	O60346	dephosphorylation	down-regulates quantity	0.341	Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle	SIGNOR-237047
P37231	P00519	phosphorylation	up-regulates quantity	0.341	We show that the tyrosine kinase Abelson murine leukemia viral oncogene (cAbl) is an adipogenic key regulator. c-Abl promotes adipogenesis by phosphorylation and subsequent stabilization of PPARγ.	SIGNOR-262297
P00519	P23470	dephosphorylation	down-regulates activity	0.341	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254691
P10636	Q15759	phosphorylation	down-regulates activity	0.341	Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.\|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.	SIGNOR-279637
O15530	P08069	phosphorylation	up-regulates	0.341	Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376	SIGNOR-166710
P10915	P14780	cleavage	down-regulates quantity by destabilization	0.341	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256328
P02746	Q07021	binding	down-regulates activity	0.341	Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping.	SIGNOR-263403
Q86UR5	Q9UFD9	binding	down-regulates activity	0.341	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264360
Q8N1W1	Q14344	binding	up-regulates activity	0.341	Taken together, the results suggest that active G13 and Gq form a complex with Rgnef and that G13 and Gq are upstream activators of Rgnef.	SIGNOR-278064
P03372	Q14164	phosphorylation	up-regulates	0.341	Here, we show that ikkepsilon interacts with and phosphorylates estrogen receptor alpha (eralpha) on serine 167 in vitro and in vivo. As a result, ikkepsilon induces eralpha transactivation activity and enhances eralpha binding to dna.	SIGNOR-161834
Q15172	P17252	phosphorylation	down-regulates activity	0.341	In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.	SIGNOR-276603
P03372	P49841	phosphorylation	up-regulates	0.34	The gsk-3 inhibitor lithium chloride was used to determine the role of gsk-3 in phosphorylation of ser-102, -104, and -106 and ser-118 in vivo and to explore the role of these serines in the regulation of eralpha function. Treatment of cells with lithium chloride resulted in dephosphorylation of ser-104 and -106 and ser-118, which suggests these serine residues as targets for gsk-3 in vivo. Our results further suggest that eralpha phosphorylation by gsk-3 stabilizes eralpha under resting conditions and modulates eralpha transcriptional activity upon ligand binding. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin a-cdk2 complex.	SIGNOR-139316
Q96B36	O43781	phosphorylation	down-regulates	0.34	When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40	SIGNOR-201002
P35579	P68400	phosphorylation	up-regulates	0.34	In egf-stimulated cells, the myosin-iia heavy chain is phosphorylated on the casein kinase 2 site (s1943)	SIGNOR-155987
P04040	P42684	phosphorylation	up-regulates activity	0.34	C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases	SIGNOR-101306
O43474	Q7Z6Z7	ubiquitination	down-regulates quantity by destabilization	0.34	K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.\|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.\|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase.	SIGNOR-278749
P50616	P45984	phosphorylation	down-regulates	0.34	Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro.	SIGNOR-91067
P10242	P68400	phosphorylation	down-regulates activity	0.34	For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants.	SIGNOR-250918
Q8NFH8	P06493	phosphorylation	down-regulates activity	0.34	Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.	SIGNOR-262724
Q9UJY1	P27361	phosphorylation	up-regulates activity	0.34	Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation	SIGNOR-107680
O95613	Q76N32	relocalization	up-regulates activity	0.34	We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. \|Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis	SIGNOR-275623
P60709	Q9NZI8	post transcriptional regulation	up-regulates quantity	0.34	We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.	SIGNOR-268160
P35558	P46379	acetylation	down-regulates quantity by destabilization	0.34	These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. \| indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation.	SIGNOR-267598
P18858	P68400	phosphorylation	up-regulates activity	0.34	Moreover, these data confirmed the occurrence of Ser66 phosphorylation, which was previously studied with a specific monoclonal antibody (23).	SIGNOR-103258
Q9UD71	P68400	phosphorylation	up-regulates activity	0.34	Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. \| Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase	SIGNOR-250927
P05019	Q9UBK2	transcriptional regulation	up-regulates quantity by expression	0.34	PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy	SIGNOR-256152
Q13309	P11309	phosphorylation	up-regulates activity	0.34	We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27.	SIGNOR-259819
Q92934	Q02156	phosphorylation	down-regulates	0.34	Pkcs phosphorylate bad under in vitro conditions, and the association of phosphorylated bad with pkc-mu or pkc-epsilon, as shown by immunoprecipitation, indicated direct involvement of pkcs in bad phosphorylation. To confirm these results, cells overexpressing pegfp-n1, wt-bad, or bad with a single site mutated (ser112ala;ser136ala;ser155ala), two sites mutated (ser(112/136)ala;ser(112/155)ala;ser(136/155)ala), or the triple mutant were tested. Igf-i protected completely against rapamycin-induced apoptosis in cells overexpressing wt-bad and mutants having either one or two sites of phosphorylation mutated	SIGNOR-163908
Q8TDN4	P31749	phosphorylation	down-regulates activity	0.34	Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex.Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis.	SIGNOR-276756
P27540	P68400	phosphorylation	down-regulates	0.34	Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.	SIGNOR-140034
P06850	P03372	transcriptional regulation	up-regulates quantity by expression	0.34	Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.\|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.	SIGNOR-268721
P19174	Q13470	binding	up-regulates quantity	0.34	GST-protein precipitations from cell lysates confirmed that GST-PLC-gamma1(SH3) associated with endogenously expressed Tnk1.	SIGNOR-273864
O43294	P06241	phosphorylation	up-regulates activity	0.34	Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.	SIGNOR-262875
P08047	P68400	phosphorylation	down-regulates activity	0.34	Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. \| Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.	SIGNOR-250954
P16615	Q14432	binding	down-regulates activity	0.34	Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2.\|PDE3A co-localized with PLB, SERCA2, and an AKAP18 variant\|our studies show that PDE3-selective inhibition (but not PDE4 inhibition) potentiates the phosphorylation of PLB by endogenous PKA and stimulation of SERCA2 activity and Ca2+ uptake in SR-enriched vesicles prepared from human myocardium.	SIGNOR-262051
Q9P0J1	P24752	acetylation	down-regulates activity	0.34	We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)	SIGNOR-267635
P48730	Q13315	phosphorylation	up-regulates activity	0.34	These results elucidated the specificity of this in vivo degradation assay, and further implicated that CKI\u03b4-dependent phosphorylation events is the major signaling route through which DNA damage-dependent activation of ATM might control timely turnover of Mdm2 during genotoxic stress. (A) ATM-mediated phosphorylation of CK1\u03b4 promotes CK1\u03b4 nuclear localization.\|We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKI\u03b4 at two well-conserved S/TQ sites, which promotes CKI\u03b4 nuclear localization to increase CKI\u03b4-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCF\u03b2-TRCP.	SIGNOR-279504
P63092	O15303	binding	up-regulates activity	0.34	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264084
P12882	Q14814	transcriptional regulation	up-regulates quantity by expression	0.34	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238751
Q15139	P00519	phosphorylation	up-regulates	0.339	By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd	SIGNOR-99255
Q07817	O14920	phosphorylation	down-regulates quantity	0.339	We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.\|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .	SIGNOR-279529
P05067	Q86TM6	ubiquitination	down-regulates quantity by destabilization	0.339	Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients.	SIGNOR-278616
Q15796	O96013	phosphorylation	down-regulates quantity by destabilization	0.339	In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation.	SIGNOR-279084
P57737	P12931	phosphorylation	up-regulates activity	0.339	We establish that Src activity is indispensable for the interaction of Crn7 with Golgi membranes. Crn7 binds Src in vivo and can be phosphorylated by recombinant Src in vitro. We demonstrate that tyrosine-758 is the major Src phosphorylation site.	SIGNOR-274005
Q13588	Q8WU20	binding	up-regulates	0.339	Complex formation between grb2 and frs2_ is mediated by y196, y306, y349, and y392 of frs2_ (designated direct grb2-binding sites;ref. 1). In addition, frs2_ recruits grb2 indirectly by means of the protein tyrosine phosphatase shp2 by way of residues y436 and y471 (designated shp2-binding sites;ref. 2).	SIGNOR-87169
P10914	Q02086	binding	up-regulates activity	0.339	Sp2 could be also able to interact with IRF-1 and this interaction is also observed on DNA indicating that by this way Sp2 is able to modulate IRF-1 transcriptional activity.	SIGNOR-226478

P47736

Q9Y297

0

ubiquitination

down-regulates

0.342

Here, we demonstrated that rap1gap is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of rap1gap requires the plk1 kinase and _-trcp ubiquitin ligase complex.

SIGNOR-203548

P54274

Q8TDX7

0

phosphorylation

up-regulates activity

0.342

Using KR-TRF2 to induce telomeric DNA damage, we found that TRF1 degradation was also exacerbated when ATM was inhibited after damage induction (55.2% of mock treated cells) (XREF_FIG), indicating that the ATM signal pathway is required for Nek7 mediated TRF1 stabilization.|We show that Nek7 phosphorylates TRF1 at Ser114 and in turn maintains stability of the shelterin complex at telomeres.

SIGNOR-278447

P09884

P09874

0

binding

up-regulates activity

0.342

We provide evidence that in proliferating cells: (i) PARP is physically associated with the catalytic subunit of the DNA polymerase α–primase tetramer, an association confirmed by confocal microscopy, demonstrating that both enzymes are co-localized at the nuclear periphery of HeLa cells.|(iii) PARP-deficient cells derived from PARP knock-out mice exhibited reduced DNA polymerase activity,

SIGNOR-261270

P08263

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.342

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256278

Q7Z3C6

P12931

0

phosphorylation

up-regulates activity

0.342

Src phosphorylates mATG9 at Tyr8 to maintain its endocytic and constitutive trafficking in unstressed conditions. In response to starvation, phosphorylation of mATG9 at Tyr8 by Src and at Ser14 by ULK1 functionally cooperate to promote interactions between mATG9 and the AP1/2 complex, leading to redistribution of mATG9 from the plasma membrane and juxta-nuclear region to the peripheral pool for autophagy initiation.

SIGNOR-266367

P26358

P24941

0

phosphorylation

up-regulates

0.342

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173681

P49840

Q05655

0

phosphorylation

down-regulates

0.342

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115722

P15311

Q15475

0

transcriptional regulation

up-regulates quantity

0.342

We now show that the gene encoding Ezrin is a direct transcriptional target of Six1.

SIGNOR-259374

P31939

P50552

0

phosphorylation

up-regulates activity

0.342

ATIC and VASP phosphorylation is dependent on NPM-ALK kinase activity.

SIGNOR-276172

Q14765

P52564

0

phosphorylation

up-regulates activity

0.342

MKK6, phosphorylate STAT4 on serine 721. IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity.

SIGNOR-251425

P15311

P41743

0

phosphorylation

up-regulates

0.342

Pkciota phosphorylated ezrin on t567 in vitro, and in sf9 cells that do not activate human ezrin. we conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by pkciota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.

SIGNOR-160855

P50148

Q96LB2

0

binding

up-regulates activity

0.342

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-257384

Q02535

P24941

0

phosphorylation

down-regulates

0.342

We now show that an analogous cell-cycle-regulated phosphorylation of id3 alters the specificity of id3 for abrogating both e-box-dependent bhlh homo- or heterodimer complex formation in vitro and e-box-dependent reporter gene function in vivo._

SIGNOR-53306

Q9UQB8

Q14678

0

binding

down-regulates activity

0.342

In this study, we report that Kank disrupts the function of active Rac1 through IRSp53. The binding between IRSp53 and Kank inhibits the association of active Rac1 with IRSp53 rather than the association of active cdc42 with IRSp53. Kank inhibits the formation of lamellipodia and membrane ruffles induced by active Rac1 in NIH3T3 cells. Kank interacts with IRSp53 through their coiled-coil domains. Kank affected the interaction between IRSp53 and Rac1 and partially affected that between IRSp53 and cdc42 (Fig. 3).

SIGNOR-265553

O15105

O15379

0

binding

up-regulates

0.342

We show here that smad7 can form a complex with endogenous histone deacetylase proteins hdac-1 and hdac-3 in nih 3t3 mouse fibroblast cells

SIGNOR-199967

P49768

P55210

0

cleavage

up-regulates activity

0.342

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261757

Q9H867

Q9BZE9

0

binding

up-regulates

0.342

In the case of vcp, methylation by mettl21d was stimulated by the addition of the ubx cofactor aspscr1, which we show directly interacts with the methyltransferase.

SIGNOR-200572

P10163

Q96L73

0

transcriptional regulation

up-regulates quantity by expression

0.342

We here demonstrate that NSD1 could bind to the promoter regions of PRB4 and activate promoter activity by reducing the binding of H3K27me2 and increasing the binding of H3K36me2 on PRB4 promoter.

SIGNOR-268459

P31749

P10586

0

dephosphorylation

down-regulates

0.342

Knock-down of lar by the l3 sirna probe markedly inhibited the insulin-stimulated increase in the phosphorylation of protein kinase b (pkb, also called akt) on serine 473 by >90%

SIGNOR-137246

Q00987

O43293

0

phosphorylation

up-regulates quantity by stabilization

0.342

Zip kinase was able to phosphorylate mdm2 at ser166, a site previously reported to be modified by akt kinase, thus demonstrating that zip kinase is a bona fide mdm2-binding protein.

SIGNOR-123159

O00308

Q07912

0

phosphorylation

up-regulates activity

0.342

ACK1 phosphorylates WWP2 at the 2, 3-linker and partially activates the ubiquitination ligase activity.|Activation of E3 ubiquitin ligase WWP2 by non-receptor tyrosine kinase ACK1.

SIGNOR-279302

Q7KZF4

Q12772

0

transcriptional regulation

up-regulates quantity by expression

0.342

These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.

SIGNOR-259136

P98164

P08253

0

binding

up-regulates quantity

0.342

We show that megalin/LRP-2 acts as an endocytic receptor for proMMP-2:TIMP-2 complex. We found that RAP, an antagonist of the LDL receptor family18, competed with binding of proMMP-2:TIMP-2 complex onto rat BN16 epithelial cells.

SIGNOR-265255

P53602

P38646

0

binding

down-regulates activity

0.342

Mortalin binds to mevalonate pyrophosphate decarboxyl ase in mammalian cell. Mot-2 inactivates MPD resulting in decreased amounts of the steady state Ras protein.

SIGNOR-265890

P25963

Q9UN86

0

relocalization

down-regulates activity

0.342

IkappaBalpha interacts with G3BP2 both in vivo and in vitrothrough the IkappaBalpha CRS. Overexpression of G3BP2 directly promotes retention of IkappaBalpha in the cytoplasm.

SIGNOR-260985

P04183

Q9UM11

0

binding

down-regulates quantity by destabilization

0.342

We show that hTK1 is degraded via a ubiquitin-proteasome pathway in mammalian cells and that anaphase-promoting complex/cyclosome (APC/C) activator Cdh1 is not only a necessary but also a rate-limiting factor for mitotic degradation of hTK1. By in vitro ubiquitinylation assays, we demonstrated that hTK1 is targeted for degradation by the APC/C-Cdh1 ubiquitin ligase dependent on this KEN box motif.

SIGNOR-272945

Q9Y2Y9

Q13523

0

phosphorylation

down-regulates

0.342

Using yeast two-hybrid screening of a human thymus cdna library, prp4, a serine/threonine protein kinase, was identified as a klf13-binding protein...coexpression of prp4 and klf13 increases nuclear localization of klf13 and ccl5 transcription.

SIGNOR-154951

P08588

Q9HD26

0

relocalization

down-regulates

0.342

Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell

SIGNOR-128791

Q8N6P7

Q6X9E4

0

binding

down-regulates quantity by destabilization

0.342

FBXW12 causes depletion of endogenous and plasmid-derived IL-22R in lung epithelia, binds the E3 ligase constituent Skp-1, and facilitates ubiquitination of IL-22R in vitro.

SIGNOR-272426

O00327

P11387

0

transcriptional regulation

down-regulates quantity by repression

0.342

We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition.

SIGNOR-277354

P33076

P27361

0

phosphorylation

up-regulates

0.341

We found that in these cells, lipopolysaccharide stimulates the expression of mhc ii genes via the activation of erk1/2, which is mediated by toll-like receptor 4. Erk1/2 then phosphorylates the serine at position 357, which is located in a degron of ciita isoform 1 that leads to its monoubiquitylation.

SIGNOR-150545

Q09472

Q9UK99

0

binding

down-regulates quantity by destabilization

0.341

O clarify the role of PML in transcription regulation, we purified the PML complex and identified Fbxo3 (Fbx3), Skp1, and Cullin1 as novel components of this complex. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway.

SIGNOR-271742

Q9H9S0

Q9HCS4

0

transcriptional regulation

down-regulates quantity by repression

0.341

These experiments showed that Tcf3 is associated with chromatin in the Nanog promoter regions and that the DNA-binding activity of Tcf3 was required for repression.

SIGNOR-266081

Q13541

P68400

0

phosphorylation

down-regulates

0.341

Phosphorylation at s112 directly affects binding of 4e-bp1 to eif4e without influencing phosphorylation of other sites.

SIGNOR-98280

Q01196

P06493

0

phosphorylation

up-regulates

0.341

Phosphorylation of runx1 on ser-303 by cdks leads its ubiquitin-mediated degradation during g2/m (19). We developed additional evidence that cdks phosphorylate ser-303 and found that ser-48 and ser-424 are also substrates of cdk1/cyclin b and cdk6/cyclin d3. Moreover, we demonstrated that phosphorylation of ser-48, ser-303, and ser-424 strengthens the ability of runx1 to activate transcription and to stimulate proliferation of the ba/f3 hematopoietic cell line (20).

SIGNOR-169322

O15516

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.341

We have identified a conserved cluster of serines that include, Ser431, which is a prerequisite phosphorylation site for the generation of BMAL dependent phospho-primed CLOCK and for the potential GSK-3 phosphorylation at Ser427.

SIGNOR-276270

Q9Y5X2

P23458

0

phosphorylation

up-regulates activity

0.341

IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.

SIGNOR-273647

Q9NR28

P53779

0

phosphorylation

down-regulates

0.341

Here we demonstrate that jnk3 can phosphorylate smac. Phosphorylation of smac by jnk3 attenuates its interaction with xiap. These results suggest that jnk3 activity can attenuate the progression of apoptosis through a novel mechanism of action, the down-regulation of interaction between smac and xiap.

SIGNOR-157280

Q9UQL6

Q13131

0

phosphorylation

down-regulates

0.341

Another recently described set of transcriptional regulators targeted by ampk and its related family members across a range of eukaryotes are the class iia family of histone deacetylases (hdacs)

SIGNOR-176479

Q8TAP9

P06493

0

phosphorylation

up-regulates

0.341

Ttdn1 is phosphorylated by cdk1 in vitro and in vivo. Ttdn1 is phosphorylated at multiple residues, including ser93 and ser104. Mutation of thr120 of ttdn1 abolishes its interaction with plk1, suggesting phosphorylation of thr120 in the consensus plk1-binding motif is required for its interaction with plk1

SIGNOR-153308

Q02363

Q9Y574

0

polyubiquitination

down-regulates quantity by destabilization

0.341

Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion.

SIGNOR-272053

P12004

P00533

0

phosphorylation

up-regulates

0.341

Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions.

SIGNOR-150852

Q13443

P50281

0

cleavage

down-regulates quantity by destabilization

0.341

Here we show that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9|Western blotting using antibodies against ectodomain of ADAM9 detected a fragment (around 26 kDa) of ADAM9 in the conditioned culture medium from cells cotransfected with wild-type MT1-MMP, but not in that with catalytic activity-dead MT1-MMP (Figure 6A, top).

SIGNOR-260301

P07355

Q5T6F2

0

ubiquitination

down-regulates quantity

0.341

UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination

SIGNOR-261314

Q01130

P61011

0

binding

up-regulates activity

0.341

We have now demonstrated that p54 interacts not only with SC35 and ASF/SF2 but also with U2AF. Pairwise interactions between p54 and other RS domain-containing spliceosomal proteins in comparison with SC35 and ASF/SF2 as detected by the yeast two-hybrid interaction assay. . It is conceivable that p54 can mediate 59 and 39 splice site interaction by interacting directly with U2AF65 associated with the 39 splice site and at the same time interact with other SR proteins, such as ASF/SF2 and SC35, which in turn interact with U1-70K. In this scenario, p54 is different from SC35 or ASF/SF2 in that it cannot directly interact with the 59 component (U1-70K) but can interact with the protein associated with the 39 splice site (U2AF65).

SIGNOR-261160

O15350

P46777

0

binding

up-regulates

0.341

We report that rpl5 and rpl11 can also enhance the transcriptional activity of a p53 homolog tap73

SIGNOR-205517

Q04206

Q9H000

0

ubiquitination

down-regulates quantity by destabilization

0.341

MKRN2 promotes p65 ubiquitination and degradation through RING finger domain.

SIGNOR-278591

P19544

P17612

0

phosphorylation

down-regulates

0.341

Pka phosphorylated wt1 at ser-365 and ser-393 in vitro, as well as at additional sites, and this phosphorylation abolished the dna-binding activity of wt1 in vitro. Using wt1 mutants in which ser-365 and ser-393 were mutated to ala individually and in combination, we showed that phosphorylation of these sites was critical for inhibition of dna binding in vivo.

SIGNOR-53172

P23443

Q13362

0

binding

down-regulates

0.341

The human homolog of pp2a-b', ppp2r5c, also counteracts s6k1 phosphorylation, indicating a conserved mechanism in mammals

SIGNOR-165224

P21860

Q00535

0

phosphorylation

up-regulates activity

0.341

We demonstrated that Cdk5 phosphorylated Ser-1176 in the neuregulin receptor ErbB2 and phosphorylated Thr-871 and Ser-1120 in the ErbB3 receptor. We identified the Ser-1120 sequence RSRSPR in ErbB3 as a novel phosphorylation consensus sequence of Cdk5. Finally, we found that Cdk5 activity is involved in neuregulin-induced Akt activity and neuregulin-mediated neuronal survival.

SIGNOR-250663

Q92974

Q9ULJ8

0

binding

up-regulates activity

0.341

The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc

SIGNOR-269177

Q05682

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.341

Together, these data demonstrate that phosphorylation of caldesmon on Ser527 by Cdk5 serves to down regulate its stability.

SIGNOR-280215

P06127

P05129

0

phosphorylation

up-regulates

0.341

Cd5 is a good pkc substrate. Phosphorylation of cd5 is necessary for cd5-mediated lipid second messenger generation.

SIGNOR-85183

Q6WKZ4

Q7KZI7

0

phosphorylation

up-regulates quantity

0.341

We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.

SIGNOR-273676

P05771

O60346

0

dephosphorylation

down-regulates quantity

0.341

Here we show that the two PHLPP isoforms, PHLPP1 and PHLPP2, also dephosphorylate the hydrophobic motif on PKC betaII, an event that shunts PKC to the detergent-insoluble fraction, effectively terminating its life cycle

SIGNOR-237047

P37231

P00519

0

phosphorylation

up-regulates quantity

0.341

We show that the tyrosine kinase Abelson murine leukemia viral oncogene (cAbl) is an adipogenic key regulator. c-Abl promotes adipogenesis by phosphorylation and subsequent stabilization of PPARγ.

SIGNOR-262297

P00519

P23470

0

dephosphorylation

down-regulates activity

0.341

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254691

P10636

Q15759

0

phosphorylation

down-regulates activity

0.341

Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.

SIGNOR-279637

O15530

P08069

0

phosphorylation

up-regulates

0.341

Previous studies indicate that optimal activation of PDK1 requires phosphorylation of Tyr373/376 (11, 12, 14, 17), and growth factor receptor activation leads to PDK1 recruitment to the plasma membrane, followed by sequential phosphorylation of Tyr9 and then Tyr373/376

SIGNOR-166710

P10915

P14780

0

cleavage

down-regulates quantity by destabilization

0.341

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

SIGNOR-256328

P02746

Q07021

0

binding

down-regulates activity

0.341

Previous studies have shown that gC1qR inhibits aggregated IgG-mediated complement activation by binding to the gC1q site on C1q, thereby preventing IgG from binding to the gh’s (28), suggesting that the binding sites for gC1qR and IgG on C1q may be identical or at least overlapping.

SIGNOR-263403

Q86UR5

Q9UFD9

0

binding

down-regulates activity

0.341

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264360

Q8N1W1

Q14344

0

binding

up-regulates activity

0.341

Taken together, the results suggest that active G13 and Gq form a complex with Rgnef and that G13 and Gq are upstream activators of Rgnef.

SIGNOR-278064

P03372

Q14164

0

phosphorylation

up-regulates

0.341

Here, we show that ikkepsilon interacts with and phosphorylates estrogen receptor alpha (eralpha) on serine 167 in vitro and in vivo. As a result, ikkepsilon induces eralpha transactivation activity and enhances eralpha binding to dna.

SIGNOR-161834

Q15172

P17252

0

phosphorylation

down-regulates activity

0.341

In this study, we identified a novel phosphorylation site at Ser(41) of B56α. This phosphoamino acid residue was efficiently phosphorylated in vitro by PKCα.

SIGNOR-276603

P03372

P49841

0

phosphorylation

up-regulates

0.34

The gsk-3 inhibitor lithium chloride was used to determine the role of gsk-3 in phosphorylation of ser-102, -104, and -106 and ser-118 in vivo and to explore the role of these serines in the regulation of eralpha function. Treatment of cells with lithium chloride resulted in dephosphorylation of ser-104 and -106 and ser-118, which suggests these serine residues as targets for gsk-3 in vivo. Our results further suggest that eralpha phosphorylation by gsk-3 stabilizes eralpha under resting conditions and modulates eralpha transcriptional activity upon ligand binding. Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin a-cdk2 complex.

SIGNOR-139316

Q96B36

O43781

0

phosphorylation

down-regulates

0.34

When dyrk3 is active, it allows stress granule dissolution, releasing mtorc1 for signaling and promoting its activity by directly phosphorylating the mtorc1 inhibitor pras40

SIGNOR-201002

P35579

P68400

0

phosphorylation

up-regulates

0.34

In egf-stimulated cells, the myosin-iia heavy chain is phosphorylated on the casein kinase 2 site (s1943)

SIGNOR-155987

P04040

P42684

0

phosphorylation

up-regulates activity

0.34

C-abl and arg phosphorylated catalase at tyr231 and tyr386 in vitrocatalase is a major effector in the defense of aerobic cells against oxidative stress. Recent studies have shown that catalase activity is stimulated by the c-abl and arg tyrosine kinases

SIGNOR-101306

O43474

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.34

K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase.

SIGNOR-278749

P50616

P45984

0

phosphorylation

down-regulates

0.34

Biochemical analyses have then shown that erk mapk (erk2) and jnk/sapk (jnk2) bind to and phosphorylate tob in vitro.

SIGNOR-91067

P10242

P68400

0

phosphorylation

down-regulates activity

0.34

For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants.

SIGNOR-250918

Q8NFH8

P06493

0

phosphorylation

down-regulates activity

0.34

Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.

SIGNOR-262724

Q9UJY1

P27361

0

phosphorylation

up-regulates activity

0.34

Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation

SIGNOR-107680

O95613

Q76N32

0

relocalization

up-regulates activity

0.34

We also found that Cep68 forms a complex with Cep215 (also known as Cdk5Rap2) and PCNT (also known as pericentrin), two PCM (pericentriolar material) proteins involved in centriole engagement. |Cep68 stabilization increases the amount of PCNT at metaphase centrosomes, but does not affect its removal at the end of mitosis

SIGNOR-275623

P60709

Q9NZI8

0

post transcriptional regulation

up-regulates quantity

0.34

We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.

SIGNOR-268160

P35558

P46379

0

acetylation

down-regulates quantity by destabilization

0.34

These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation.

SIGNOR-267598

P18858

P68400

0

phosphorylation

up-regulates activity

0.34

Moreover, these data confirmed the occurrence of Ser66 phosphorylation, which was previously studied with a specific monoclonal antibody (23).

SIGNOR-103258

Q9UD71

P68400

0

phosphorylation

up-regulates activity

0.34

Study of [Plphosphate release during manual Edman degradation confirmed that the phosphorylated residues in rat DARPP-32 were Ser45 and Ser102. | Phosphorylation by casein kinase II did not affect the potency of DARPP-32 as an inhibitor of protein phosphatase-1, which depended only on phosphorylation of Thr34 by cAMP-dependent protein kinase. However, phosphorylation of DARPP-32 by casein kinase II facilitated phosphorylation of Thr34 by cAMP-dependent protein kinase

SIGNOR-250927

P05019

Q9UBK2

0

transcriptional regulation

up-regulates quantity by expression

0.34

PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy

SIGNOR-256152

Q13309

P11309

0

phosphorylation

up-regulates activity

0.34

We found that expression of Pim-1 increases the level of Skp2 through direct binding and phosphorylation of multiple sites on this protein. Along with known Skp2 phosphorylation sites including Ser(64) and Ser(72), we have identified Thr(417) as a unique Pim-1 phosphorylation target. Phosphorylation of Thr(417) controls the stability of Skp2 and its ability to degrade p27.

SIGNOR-259819

Q92934

Q02156

0

phosphorylation

down-regulates

0.34

Pkcs phosphorylate bad under in vitro conditions, and the association of phosphorylated bad with pkc-mu or pkc-epsilon, as shown by immunoprecipitation, indicated direct involvement of pkcs in bad phosphorylation. To confirm these results, cells overexpressing pegfp-n1, wt-bad, or bad with a single site mutated (ser112ala;ser136ala;ser155ala), two sites mutated (ser(112/136)ala;ser(112/155)ala;ser(136/155)ala), or the triple mutant were tested. Igf-i protected completely against rapamycin-induced apoptosis in cells overexpressing wt-bad and mutants having either one or two sites of phosphorylation mutated

SIGNOR-163908

Q8TDN4

P31749

0

phosphorylation

down-regulates activity

0.34

Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex.Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis.

SIGNOR-276756

P27540

P68400

0

phosphorylation

down-regulates

0.34

Here, we show that arnt and alt arnt proteins are differentially phosphorylated by protein kinase ckii in vitro. Phosphorylation had an inhibitory effect on dna-binding to an e-box probe by alt arnt, but not arnt, homodimers. This inhibitory phosphorylation occurs through ser77.

SIGNOR-140034

P06850

P03372

0

transcriptional regulation

up-regulates quantity by expression

0.34

Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro.

SIGNOR-268721

P19174

Q13470

0

binding

up-regulates quantity

0.34

GST-protein precipitations from cell lysates confirmed that GST-PLC-gamma1(SH3) associated with endogenously expressed Tnk1.

SIGNOR-273864

O43294

P06241

0

phosphorylation

up-regulates activity

0.34

Hic-5 is a CAKbeta-binding protein localized at focal adhesions. Here we show that overexpression of CAKbeta or Fyn, but not FAK, enhanced the tyrosine phosphorylation of coexpressed Hic-5 in COS-7 cells. The Y60F mutant of Hic-5 was not phosphorylated, and Hic-5 phosphorylated on tyrosine 60 was bound specifically to the SH2 domain of Csk. Specific phosphorylation of Hic-5 by CAKbeta and Fyn may activate a signaling pathway mediated by Hic-5.

SIGNOR-262875

P08047

P68400

0

phosphorylation

down-regulates activity

0.34

Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity. | Mutation of a consensus CKII site at amino acid 579, within the second zinc finger, eliminates phosphorylation of this site and the CKII-mediated inhibition of Sp1 binding.

SIGNOR-250954

P16615

Q14432

0

binding

down-regulates activity

0.34

Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2.|PDE3A co-localized with PLB, SERCA2, and an AKAP18 variant|our studies show that PDE3-selective inhibition (but not PDE4 inhibition) potentiates the phosphorylation of PLB by endogenous PKA and stimulation of SERCA2 activity and Ca2+ uptake in SR-enriched vesicles prepared from human myocardium.

SIGNOR-262051

Q9P0J1

P24752

0

acetylation

down-regulates activity

0.34

We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)

SIGNOR-267635

P48730

Q13315

0

phosphorylation

up-regulates activity

0.34

These results elucidated the specificity of this in vivo degradation assay, and further implicated that CKI\u03b4-dependent phosphorylation events is the major signaling route through which DNA damage-dependent activation of ATM might control timely turnover of Mdm2 during genotoxic stress. (A) ATM-mediated phosphorylation of CK1\u03b4 promotes CK1\u03b4 nuclear localization.|We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKI\u03b4 at two well-conserved S/TQ sites, which promotes CKI\u03b4 nuclear localization to increase CKI\u03b4-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCF\u03b2-TRCP.

SIGNOR-279504

P63092

O15303

0

binding

up-regulates activity

0.34

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264084

P12882

Q14814

0

transcriptional regulation

up-regulates quantity by expression

0.34

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

SIGNOR-238751

Q15139

P00519

0

phosphorylation

up-regulates

0.339

By using a phospho-specific antibody, we show that abl directly phosphorylates pkd at tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of pkd

SIGNOR-99255

Q07817

O14920

0

phosphorylation

down-regulates quantity

0.339

We present evidence for a signaling network that involves phosphorylation and reduction of Bcl-xL by IKKbeta, and subsequent activation of caspases, which can cleave Htt.|We propose that IKKbeta reduces Bcl-xL levels by phosphorylation (XREF_FIG), a modification known to promote Bcl-xL degradation .

SIGNOR-279529

P05067

Q86TM6

0

ubiquitination

down-regulates quantity by destabilization

0.339

Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients.

SIGNOR-278616

Q15796

O96013

0

phosphorylation

down-regulates quantity by destabilization

0.339

In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation.

SIGNOR-279084

P57737

P12931

0

phosphorylation

up-regulates activity

0.339

We establish that Src activity is indispensable for the interaction of Crn7 with Golgi membranes. Crn7 binds Src in vivo and can be phosphorylated by recombinant Src in vitro. We demonstrate that tyrosine-758 is the major Src phosphorylation site.

SIGNOR-274005

Q13588

Q8WU20

0

binding

up-regulates

0.339

Complex formation between grb2 and frs2_ is mediated by y196, y306, y349, and y392 of frs2_ (designated direct grb2-binding sites;ref. 1). In addition, frs2_ recruits grb2 indirectly by means of the protein tyrosine phosphatase shp2 by way of residues y436 and y471 (designated shp2-binding sites;ref. 2).

SIGNOR-87169

P10914

Q02086

0

binding

up-regulates activity

0.339

Sp2 could be also able to interact with IRF-1 and this interaction is also observed on DNA indicating that by this way Sp2 is able to modulate IRF-1 transcriptional activity.

SIGNOR-226478