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
P68400	P55010	1	phosphorylation	up-regulates	0.394	We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.	SIGNOR-141159
P09758	O95471	1	binding	up-regulates quantity	0.394	In summary, our findings provide evidence that Trop-2 is phosphorylated at Ser-322 by PKCα/δ and that this phosphorylation enhances cell motility and decreases claudin-7 localization to cellular borders.	SIGNOR-273822
Q99612	P18847	1	transcriptional regulation	up-regulates quantity by expression	0.394	KLF6 binds directly to and activates the ATF3 promoter.	SIGNOR-266051
Q05513	P14598	1	phosphorylation	up-regulates	0.394	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89280
O75925	Q13485	1	sumoylation	up-regulates	0.394	These data demonstrate that pias1 protein positively modulates tgf-beta responses as a sumo e3 ligase for smad4	SIGNOR-123462
P49841	P98170	1	phosphorylation	up-regulates activity	0.394	We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.	SIGNOR-277390
P06493	Q8IX90	1	phosphorylation	up-regulates activity	0.394	Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].\|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.	SIGNOR-278376
Q9Y297	P30291	1	binding	down-regulates	0.394	Scfb-trcp continues to have a role in this phase, however, through its induced degradation of the cdk1 inhibitor, wee1.	SIGNOR-128439
P28482	P17480	1	phosphorylation	down-regulates	0.394	Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna	SIGNOR-112809
P78368	O15534	1	phosphorylation	down-regulates	0.394	Ck1_ and ck1_2 can promote proteasome-dependent per1 degradation in mammalian tissue culture cells, and their removal by rnai leads to an increased abundance of per1.	SIGNOR-137751
P00533	P09874	1	phosphorylation	up-regulates activity	0.394	EGFR and MET heterodimer interacts with and phosphorylates PARP1.	SIGNOR-279169
P31749	Q7Z6J0	1	phosphorylation	down-regulates	0.394	We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac, as does phosphomimetic s304d and s304e mutation of posh.	SIGNOR-252501
P24941	P48431	1	phosphorylation	up-regulates activity	0.394	Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.	SIGNOR-279448
P61019	Q15643	1	binding	up-regulates activity	0.394	Vesicle-associated Rab2 then mediates attachment to the Rab2 binding site within the central coiled-coil region of GMAP-210, bringing the vesicle into closer proximity to the target membrane. GMAP-210 function in vivo is dependent upon its ability to tether membranes, which is mediated exclusively by the amino-terminal ALPS motif. Binding to Rab2 is also important for GMAP-210 function, although it is dispensable for tethering per se.	SIGNOR-261300
P06400	P15172	2	binding	up-regulates	0.394	Cycline/cdk2 blocks myod-induced gene expression through the phosphorylation of rb, preventing rb from binding and transactivating myod, and triggering s phase entry instead of differentiation.	SIGNOR-176563
P15172	P06400	2	transcriptional regulation	up-regulates quantity by expression	0.394	Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator.	SIGNOR-238532
Q92949	O14645	1	transcriptional regulation	up-regulates quantity by expression	0.394	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266933
Q6UW88	Q15303	1	binding	up-regulates	0.394	Areg (amphiregulin), btc (beta-cellulin), egf, epgn (epigen), ereg (epiregulin), hbegf, nrg1, nrg2, nrg3, nrg4 and tgfa (tgfalpha) constitute egf family ligands for erbb family receptors.	SIGNOR-147835
Q6ZN28	P08581	1	transcriptional regulation	up-regulates quantity by expression	0.394	Human colon carcinoma SW480 cells express virtually no MACC1. MACC1 cDNA transfection led not only to strong increases in MACC1 mRNA expression (Fig. 3a), but also to a 40-fold upregulation of the HGF receptor MET mRNA expression (Fig. 3b). This was confirmed on the protein level	SIGNOR-266058
Q15678	P56945	1	dephosphorylation	down-regulates	0.394	We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation	SIGNOR-197923
P53350	Q96R06	1	phosphorylation	up-regulates activity	0.394	Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.\|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.	SIGNOR-279423
Q00987	P63092	1	binding	down-regulates activity	0.394	Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content.	SIGNOR-278070
P17252	Q92686	1	phosphorylation	up-regulates activity	0.394	Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.	SIGNOR-248913
Q96EP1	Q13547	1	polyubiquitination	down-regulates quantity by destabilization	0.394	Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.	SIGNOR-271465
P12931	Q07954	1	phosphorylation	up-regulates activity	0.394	We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras	SIGNOR-101535
P06241	Q15438	1	phosphorylation	up-regulates activity	0.394	Fyn directly binds, phosphorylates, and activates cytohesin-1.	SIGNOR-280015
P40337	Q9H257	1	binding	down-regulates activity	0.393	We found that pVHL associates with the NF-kappaB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C terminus by CK2.	SIGNOR-257603
P17252	Q9BZL6	1	phosphorylation	up-regulates activity	0.393	Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.\|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead.	SIGNOR-275955
P31749	Q9H4A3	1	phosphorylation	up-regulates	0.393	Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.	SIGNOR-252481
P35555	O95967	1	binding	down-regulates activity	0.393	Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.	SIGNOR-251860
P31749	P23588	1	phosphorylation	up-regulates	0.393	Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.	SIGNOR-252520
Q15418	P46527	1	phosphorylation	up-regulates activity	0.393	As for other PI3K effectors, RSK1 phosphorylates p27 at T198.\|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.	SIGNOR-279653
P42224	Q99102	1	transcriptional regulation	up-regulates quantity by expression	0.393	Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.	SIGNOR-254099
P17844	Q13547	1	binding	up-regulates	0.393	Wt p68 co-immunoprecipitates efficiently with hdac1, the k53r p68 does not / sumoylation is important for the interaction of p68 with hdac1 and for transcriptional repression by p68	SIGNOR-153715
Q16832	P29353	1	binding	up-regulates	0.393	Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes.	SIGNOR-140724
P51843	Q9Y618	1	binding	up-regulates activity	0.393	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271785
P12931	Q8WUM4	1	phosphorylation	down-regulates activity	0.393	Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2.	SIGNOR-263201
O14965	P00533	1	phosphorylation	up-regulates activity	0.393	Because AURKA associated with EGFR, we next investigated whether AURKA phosphorylates EGFR at Thr654 and Ser1046.\|Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells.	SIGNOR-279589
Q92585	Q06413	1	binding	up-regulates	0.393	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-144913
P51955	Q8NG66	1	phosphorylation	up-regulates	0.393	Nek2 directly phosphorylated nek11 in the c-terminal non-catalytic region and elevated nek11 kinase activity.	SIGNOR-124944
Q5S007	P46734	1	phosphorylation	up-regulates activity	0.393	LRRK2 phosphorylates MKK3 and MKK7 in vitro but has a relatively minor effect on MKK6 phosphorylation.	SIGNOR-279057
Q9BZK7	P10275	1	binding	up-regulates	0.393	We showed that tblr1 physically interacts with ar and directly occupies the androgen-response elements of the affected ar target genes in an androgen-dependent manner. / we characterized tblr1 as a coactivator of ar	SIGNOR-203235
P24752	P08559	1	acetylation	down-regulates activity	0.393	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-267633
P10909	Q8N668	1	binding	down-regulates quantity by destabilization	0.392	CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.	SIGNOR-271432
P49336	P42224	1	phosphorylation	up-regulates activity	0.392	We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation.	SIGNOR-273179
Q9H4E7	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.392	Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.	SIGNOR-253369
P08588	P38405	1	binding	up-regulates activity	0.392	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-256901
P10721	P35222	1	phosphorylation	up-regulates activity	0.392	These results suggest that active KIT can directly phosphorylate tyrosine residues of beta-catenin.	SIGNOR-278361
P49840	P20749	1	phosphorylation	down-regulates quantity by destabilization	0.392	In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway.	SIGNOR-276011
P05412	P15884	1	binding	up-regulates	0.392	Phosphorylation-dependent interaction between c-jun and tcf4;c-jun and tcf4 cooperatively activated the c-jun promoter in reporter assays	SIGNOR-138544
P42345	Q15349	1	phosphorylation	up-regulates activity	0.392	Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref	SIGNOR-279232
O75676	P01100	1	phosphorylation	up-regulates activity	0.392	Serine 374 and serine 362 are the primary sites targeted by Erk1/2 and the mitogen-activated protein kinase-activated kinases Rsk1/2 (12, 13, 37, 38, 41), respectively. Their phosphorylation leads to protein stabilization (3, 13, 20, 41). Threonine 325 and threonine 331 are secondary targets of Erk1/2; their modification occurs only when serines 362 and 374 are phosphorylated and Erk1/2 activation is sufficiently sustained (37, 38). This enhances the transcriptional activity of c-Fos	SIGNOR-263000
O75717	Q9HAW4	1	binding	up-regulates activity	0.392	And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA.	SIGNOR-262665
O15297	Q12888	1	dephosphorylation	down-regulates activity	0.392	In addition, WIP1 dephosphorylates 53BP1 at Threonine 543 that was previously implicated in mediating interaction with RIF1.	SIGNOR-277046
P27361	Q12772	1	phosphorylation	up-regulates	0.392	Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.	SIGNOR-123053
Q9NZS9	P55061	1	polyubiquitination	down-regulates quantity by destabilization	0.392	BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.	SIGNOR-272778
Q9ULZ2	P42680	2	binding	up-regulates activity	0.392	In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling. BRDG1 may activate Tec by disrupting an intramolecular interaction.	SIGNOR-261819
Q07687	P35548	2	binding	down-regulates activity	0.392	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240911
O15391	P01100	1	transcriptional regulation	up-regulates quantity by expression	0.392	YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter.	SIGNOR-266212
P53350	P25490	1	phosphorylation	up-regulates	0.392	More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis	SIGNOR-200087
Q5SW24	P36897	1	binding	down-regulates	0.392	Here, we provide evidence that unlike dpr1 that modulates wnt signaling, mdpr2 negatively regulates tgf-? Signaling and promotes tgf-? Receptor degradation in lysosomes. these results suggest that mdpr2 interferes with tgf-? By directly binding to and targeting the receptors for lysosomal inhibitor-sensitive degradation.	SIGNOR-151750
P42680	Q9ULZ2	2	phosphorylation	up-regulates activity	0.392	In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.	SIGNOR-261817
P35548	Q07687	2	binding	down-regulates activity	0.392	We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.	SIGNOR-240932
Q15398	P78352	1	binding	up-regulates activity	0.392	SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.	SIGNOR-264213
P42127	O75882	1	binding	up-regulates	0.391	Attractin is a low-affinity receptor for agouti protein, but not agrp, in vitro and in vivo.	SIGNOR-85496
P15172	P15692	1	transcriptional regulation	up-regulates quantity by expression	0.391	We further demonstrate that the myogenic transcription factor, MyoD, and its heterodimeric binding proteins E12 and E47, up-regulate the expression of endogenous VEGF through direct interaction with the VEGF promoter.	SIGNOR-257598
Q9P1W9	Q92934	1	phosphorylation	down-regulates activity	0.391	All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death.	SIGNOR-249604
P48729	Q13501	1	phosphorylation	up-regulates activity	0.391	Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation.	SIGNOR-273769
P19484	Q9GZQ8	1	transcriptional regulation	up-regulates quantity by expression	0.391	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276559
Q8N726	Q13535	1	phosphorylation	up-regulates activity	0.391	Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressorInduction of ATR activity in Hs68 E2F1ER cells by endogenous ARF.	SIGNOR-134781
Q6GPH4	Q13489	1	binding	down-regulates	0.391	Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3	SIGNOR-155288
Q12904	Q9HAU4	1	binding	up-regulates activity	0.391	Here, we report that AIMP1 negatively regulates TGF-_ signaling via stabilization of Smurf2.	SIGNOR-227470
Q99626	Q07654	1	transcriptional regulation	up-regulates quantity by expression	0.391	The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells.	SIGNOR-253967
P43405	P17252	1	phosphorylation	up-regulates activity	0.391	We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2.	SIGNOR-246581
Q9Y2X7	Q02750	1	binding	up-regulates activity	0.391	We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens.	SIGNOR-261245
O95155	Q99689	1	polyubiquitination	up-regulates activity	0.391	E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.	SIGNOR-271510
Q8NG27	P84022	1	ubiquitination	down-regulates activity	0.391	In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).	SIGNOR-278832
P14416	P19086	1	binding	up-regulates activity	0.391	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-257096
Q9H4B4	Q07817	1	phosphorylation	up-regulates	0.391	Polo kinase 3 (plk3) was implicated in bcl-xl(ser49) phosphorylation. These data indicate that, during g2 checkpoint, phospho-bcl-xl(ser49) is another downstream target of plk3, acting to stabilize g2 arrest.	SIGNOR-172230
Q9UK99	Q9HCE7	1	binding	down-regulates quantity by destabilization	0.391	F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.	SIGNOR-272441
P42345	P06213	1	phosphorylation	up-regulates activity	0.391	Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.\|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR and InsR.	SIGNOR-280045
Q12923	P00519	1	dephosphorylation	down-regulates activity	0.39	We also found that PTPN13 dephosphorylates and inhibits c-Abl.\|While the above results indicated that calpain-2 could cleave PTPN13 and that PTPN13 could dephosphorylate c-Abl at tyrosine 245, they did not determine whether calpain-2-mediated cleavage of PTPN13 resulted in its inactivation and increased tyrosine phosphorylation of c-Abl at tyrosine 245.	SIGNOR-277012
P23769	P01222	1	transcriptional regulation	up-regulates quantity by expression	0.39	Pit-1, is necessary but not sufficient to allow basal transcription of the mTSHβ gene.The analysis of the mTSHβ gene described in this report provides evidence for the participation of a zinc finger factor, GATA-2, with a POU homeodomain partner, Pit-1, on a such a composite element.In summary, we have shown the requirement for at least two different classes of transcription factors to regulate mTSHβ gene expression. Both GATA-2 and Pit-1 can bind independently to the P1 region of the promoter, form a heteromeric complex with DNA, and functionally synergize to activate TSHβ promoter activity.	SIGNOR-267253
P49593	Q13153	1	dephosphorylation	down-regulates activity	0.39	The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family\|POPX Can Dephosphorylate and Downregulate PAK\| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.	SIGNOR-248530
Q15796	Q02078	1	binding	up-regulates	0.39	Our studies indicate that smad2 and 4 (smad2/4) complexes cooperate with mef2 regulatory proteins in a gal4-based one-hybrid reporter gene assay.	SIGNOR-235846
Q9P275	P06748	1	deubiquitination	up-regulates quantity by stabilization	0.39	USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation.	SIGNOR-272290
P17252	P35368	1	phosphorylation	down-regulates activity	0.39	Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.	SIGNOR-248988
P31749	P49760	1	phosphorylation	up-regulates	0.39	Akt directly binds to and phosphorylates clk2 on serine 34 and threonine 127, in vitro and in vivo.Our results suggest that akt activation controls cell survival to ionizing radiation by phosphorylating clk2, revealing an important regulatory mechanism required for promoting cell surviva	SIGNOR-167340
P46934	O43597	1	polyubiquitination	down-regulates quantity by destabilization	0.39	Endogenous and overexpressed Nedd4 polyubiquitinate Spry2 via Lys(48) on ubiquitin and decrease its stability.	SIGNOR-271425
Q15386	O75155	1	ubiquitination	down-regulates quantity by destabilization	0.39	We show that KIAA10 indeed associates with 26 S proteasomes in mammalian cells but that this interaction is likely to depend on contacts with a subunit(s) besides S2/Rpn1. Most importantly, we provide strong evidence that TIP120B (TBP-interacting protein 120B (22)) is a specific substrate that is targeted for degradation in skeletal muscle through KIAA10-catalyzed polyubiquitination.	SIGNOR-271454
P49841	Q86YF9	1	phosphorylation	up-regulates activity	0.39	Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.	SIGNOR-278251
P68400	P35221	1	phosphorylation	down-regulates	0.39	We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.	SIGNOR-161847
P23469	P28482	1	dephosphorylation	down-regulates activity	0.39	The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling\|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop	SIGNOR-248448
P78317	P08047	1	polyubiquitination	down-regulates quantity by destabilization	0.39	Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation.	SIGNOR-272720
P26441	O75462	1	binding	up-regulates	0.39	We recently demonstrated that cardiotrophin-like cytokine (clc) associates with the soluble orphan receptor cytokine-like factor-1 (clf) to form a heterodimeric cytokine that displayed activities only on cells expressing the tripartite cntf receptor on their surface	SIGNOR-106635
P19784	Q92769	1	phosphorylation	up-regulates activity	0.39	HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. \| Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.	SIGNOR-251001
Q96P31	P29350	1	binding	up-regulates activity	0.39	Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.	SIGNOR-274013
Q9UBF6	Q13794	1	ubiquitination	down-regulates activity	0.39	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271446
P31749	Q96IZ0	1	phosphorylation	down-regulates activity	0.39	Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy	SIGNOR-279668
Q00535	P12931	1	phosphorylation	up-regulates	0.39	These results present compelling evidence that cdk5/p35 kinase is responsible for the novel phosphorylation of c-src at ser75 in neuronal cells, raising the intriguing possibility that c-src acts as an effector of cdk5/p35 kinase during neuronal development.	SIGNOR-71950

P68400

P55010

1

phosphorylation

up-regulates

0.394

We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.

SIGNOR-141159

P09758

O95471

1

binding

up-regulates quantity

0.394

In summary, our findings provide evidence that Trop-2 is phosphorylated at Ser-322 by PKCα/δ and that this phosphorylation enhances cell motility and decreases claudin-7 localization to cellular borders.

SIGNOR-273822

Q99612

P18847

1

transcriptional regulation

up-regulates quantity by expression

0.394

KLF6 binds directly to and activates the ATF3 promoter.

SIGNOR-266051

Q05513

P14598

1

phosphorylation

up-regulates

0.394

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89280

O75925

Q13485

1

sumoylation

up-regulates

0.394

These data demonstrate that pias1 protein positively modulates tgf-beta responses as a sumo e3 ligase for smad4

SIGNOR-123462

P49841

P98170

1

phosphorylation

up-regulates activity

0.394

We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.

SIGNOR-277390

P06493

Q8IX90

1

phosphorylation

up-regulates activity

0.394

Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.

SIGNOR-278376

Q9Y297

P30291

1

binding

down-regulates

0.394

Scfb-trcp continues to have a role in this phase, however, through its induced degradation of the cdk1 inhibitor, wee1.

SIGNOR-128439

P28482

P17480

1

phosphorylation

down-regulates

0.394

Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna

SIGNOR-112809

P78368

O15534

1

phosphorylation

down-regulates

0.394

Ck1_ and ck1_2 can promote proteasome-dependent per1 degradation in mammalian tissue culture cells, and their removal by rnai leads to an increased abundance of per1.

SIGNOR-137751

P00533

P09874

1

phosphorylation

up-regulates activity

0.394

EGFR and MET heterodimer interacts with and phosphorylates PARP1.

SIGNOR-279169

P31749

Q7Z6J0

1

phosphorylation

down-regulates

0.394

We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac, as does phosphomimetic s304d and s304e mutation of posh.

SIGNOR-252501

P24941

P48431

1

phosphorylation

up-regulates activity

0.394

Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.

SIGNOR-279448

P61019

Q15643

1

binding

up-regulates activity

0.394

Vesicle-associated Rab2 then mediates attachment to the Rab2 binding site within the central coiled-coil region of GMAP-210, bringing the vesicle into closer proximity to the target membrane. GMAP-210 function in vivo is dependent upon its ability to tether membranes, which is mediated exclusively by the amino-terminal ALPS motif. Binding to Rab2 is also important for GMAP-210 function, although it is dispensable for tethering per se.

SIGNOR-261300

P06400

P15172

2

binding

up-regulates

0.394

Cycline/cdk2 blocks myod-induced gene expression through the phosphorylation of rb, preventing rb from binding and transactivating myod, and triggering s phase entry instead of differentiation.

SIGNOR-176563

P15172

P06400

2

transcriptional regulation

up-regulates quantity by expression

0.394

Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator.

SIGNOR-238532

Q92949

O14645

1

transcriptional regulation

up-regulates quantity by expression

0.394

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266933

Q6UW88

Q15303

1

binding

up-regulates

0.394

Areg (amphiregulin), btc (beta-cellulin), egf, epgn (epigen), ereg (epiregulin), hbegf, nrg1, nrg2, nrg3, nrg4 and tgfa (tgfalpha) constitute egf family ligands for erbb family receptors.

SIGNOR-147835

Q6ZN28

P08581

1

transcriptional regulation

up-regulates quantity by expression

0.394

Human colon carcinoma SW480 cells express virtually no MACC1. MACC1 cDNA transfection led not only to strong increases in MACC1 mRNA expression (Fig. 3a), but also to a 40-fold upregulation of the HGF receptor MET mRNA expression (Fig. 3b). This was confirmed on the protein level

SIGNOR-266058

Q15678

P56945

1

dephosphorylation

down-regulates

0.394

We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation

SIGNOR-197923

P53350

Q96R06

1

phosphorylation

up-regulates activity

0.394

Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.

SIGNOR-279423

Q00987

P63092

1

binding

down-regulates activity

0.394

Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content.

SIGNOR-278070

P17252

Q92686

1

phosphorylation

up-regulates activity

0.394

Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.

SIGNOR-248913

Q96EP1

Q13547

1

polyubiquitination

down-regulates quantity by destabilization

0.394

Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.

SIGNOR-271465

P12931

Q07954

1

phosphorylation

up-regulates activity

0.394

We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras

SIGNOR-101535

P06241

Q15438

1

phosphorylation

up-regulates activity

0.394

Fyn directly binds, phosphorylates, and activates cytohesin-1.

SIGNOR-280015

P40337

Q9H257

1

binding

down-regulates activity

0.393

We found that pVHL associates with the NF-kappaB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C terminus by CK2.

SIGNOR-257603

P17252

Q9BZL6

1

phosphorylation

up-regulates activity

0.393

Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead.

SIGNOR-275955

P31749

Q9H4A3

1

phosphorylation

up-regulates

0.393

Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.

SIGNOR-252481

P35555

O95967

1

binding

down-regulates activity

0.393

Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.

SIGNOR-251860

P31749

P23588

1

phosphorylation

up-regulates

0.393

Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.

SIGNOR-252520

Q15418

P46527

1

phosphorylation

up-regulates activity

0.393

As for other PI3K effectors, RSK1 phosphorylates p27 at T198.|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.

SIGNOR-279653

P42224

Q99102

1

transcriptional regulation

up-regulates quantity by expression

0.393

Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.

SIGNOR-254099

P17844

Q13547

1

binding

up-regulates

0.393

Wt p68 co-immunoprecipitates efficiently with hdac1, the k53r p68 does not / sumoylation is important for the interaction of p68 with hdac1 and for transcriptional repression by p68

SIGNOR-153715

Q16832

P29353

1

binding

up-regulates

0.393

Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes.

SIGNOR-140724

P51843

Q9Y618

1

binding

up-regulates activity

0.393

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271785

P12931

Q8WUM4

1

phosphorylation

down-regulates activity

0.393

Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2.

SIGNOR-263201

O14965

P00533

1

phosphorylation

up-regulates activity

0.393

Because AURKA associated with EGFR, we next investigated whether AURKA phosphorylates EGFR at Thr654 and Ser1046.|Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells.

SIGNOR-279589

Q92585

Q06413

1

binding

up-regulates

0.393

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-144913

P51955

Q8NG66

1

phosphorylation

up-regulates

0.393

Nek2 directly phosphorylated nek11 in the c-terminal non-catalytic region and elevated nek11 kinase activity.

SIGNOR-124944

Q5S007

P46734

1

phosphorylation

up-regulates activity

0.393

LRRK2 phosphorylates MKK3 and MKK7 in vitro but has a relatively minor effect on MKK6 phosphorylation.

SIGNOR-279057

Q9BZK7

P10275

1

binding

up-regulates

0.393

We showed that tblr1 physically interacts with ar and directly occupies the androgen-response elements of the affected ar target genes in an androgen-dependent manner. / we characterized tblr1 as a coactivator of ar

SIGNOR-203235

P24752

P08559

1

acetylation

down-regulates activity

0.393

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-267633

P10909

Q8N668

1

binding

down-regulates quantity by destabilization

0.392

CLU-2 is a ubiquitin binding protein (UBP) that enhances proteasome activity. sCLU promotes degradation of COMMD1. sCLU interacts with the SCF-βTrCP E3 ligase complex, serving as a scaffolding chaperone to form a multimeric protein complex that facilitates COMMD1 and I-κB ubiquitination and proteasomal degradation.

SIGNOR-271432

P49336

P42224

1

phosphorylation

up-regulates activity

0.392

We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation.

SIGNOR-273179

Q9H4E7

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.392

Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.

SIGNOR-253369

P08588

P38405

1

binding

up-regulates activity

0.392

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-256901

P10721

P35222

1

phosphorylation

up-regulates activity

0.392

These results suggest that active KIT can directly phosphorylate tyrosine residues of beta-catenin.

SIGNOR-278361

P49840

P20749

1

phosphorylation

down-regulates quantity by destabilization

0.392

In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway.

SIGNOR-276011

P05412

P15884

1

binding

up-regulates

0.392

Phosphorylation-dependent interaction between c-jun and tcf4;c-jun and tcf4 cooperatively activated the c-jun promoter in reporter assays

SIGNOR-138544

P42345

Q15349

1

phosphorylation

up-regulates activity

0.392

Subsequently, mTOR phosphorylates and activates the 70-kDa ribosomal protein S6 kinase (p70S6K), which results in increased translation either directly or indirectly by activating initiation and elongation factors, eIF-2, eIF-4E (through 4E-BP) and eEF-2 (Bodine et al. xref

SIGNOR-279232

O75676

P01100

1

phosphorylation

up-regulates activity

0.392

Serine 374 and serine 362 are the primary sites targeted by Erk1/2 and the mitogen-activated protein kinase-activated kinases Rsk1/2 (12, 13, 37, 38, 41), respectively. Their phosphorylation leads to protein stabilization (3, 13, 20, 41). Threonine 325 and threonine 331 are secondary targets of Erk1/2; their modification occurs only when serines 362 and 374 are phosphorylated and Erk1/2 activation is sufficiently sustained (37, 38). This enhances the transcriptional activity of c-Fos

SIGNOR-263000

O75717

Q9HAW4

1

binding

up-regulates activity

0.392

And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA.

SIGNOR-262665

O15297

Q12888

1

dephosphorylation

down-regulates activity

0.392

In addition, WIP1 dephosphorylates 53BP1 at Threonine 543 that was previously implicated in mediating interaction with RIF1.

SIGNOR-277046

P27361

Q12772

1

phosphorylation

up-regulates

0.392

Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity.

SIGNOR-123053

Q9NZS9

P55061

1

polyubiquitination

down-regulates quantity by destabilization

0.392

BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.

SIGNOR-272778

Q9ULZ2

P42680

2

binding

up-regulates activity

0.392

In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling. BRDG1 may activate Tec by disrupting an intramolecular interaction.

SIGNOR-261819

Q07687

P35548

2

binding

down-regulates activity

0.392

We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.

SIGNOR-240911

O15391

P01100

1

transcriptional regulation

up-regulates quantity by expression

0.392

YY2 activated the p53 promoter. However, in contrast to YY1, which represses the activity of c-Fos, YY2 increased the activity of the c-Fos promoter.

SIGNOR-266212

P53350

P25490

1

phosphorylation

up-regulates

0.392

More recently, we identified and mapped multiple phosphorylation sites in yy1, including, threonine 39, serine 118, serine 247, threonine 348 and threonine 378. The first kinase proven to phosphorylate yy1 in vivo was plk1, which phosphorylates threonine 39 during g2/m stage of the cell cycle [25]. Ck2_ is another kinase identified as constitutively phosphorylating yy1 at serine 118. This modification protects yy1 cleavage by caspase 7 during apoptosis

SIGNOR-200087

Q5SW24

P36897

1

binding

down-regulates

0.392

Here, we provide evidence that unlike dpr1 that modulates wnt signaling, mdpr2 negatively regulates tgf-? Signaling and promotes tgf-? Receptor degradation in lysosomes. these results suggest that mdpr2 interferes with tgf-? By directly binding to and targeting the receptors for lysosomal inhibitor-sensitive degradation.

SIGNOR-151750

P42680

Q9ULZ2

2

phosphorylation

up-regulates activity

0.392

In 293 cells expressing recombinant BRDG1 and various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling.

SIGNOR-261817

P35548

Q07687

2

binding

down-regulates activity

0.392

We demonstrate that dimerization by Msx and Dlx proteins is mediated through their homeodomains and that the residues required for this interaction correspond to those necessary for DNA binding. Unlike most other known examples of homeoprotein interactions, association of Msx and Dlx proteins does not promote cooperative DNA binding; instead, dimerization and DNA binding are mutually exclusive activities. Msx proteins act as transcriptional repressors and Dlx proteins act as activators, while in combination, Msx and Dlx proteins counteract each other's transcriptional activities.

SIGNOR-240932

Q15398

P78352

1

binding

up-regulates activity

0.392

SAPAPs are specifically expressed in neuronal cells and enriched in the PSD fraction. SAPAPs induce the enrichment of PSD-95/SAP90 to the plasma membrane in transfected cells. Thus, SAPAPs may have a potential activity to maintain the structure of PSD by concentrating its components to the membrane area.

SIGNOR-264213

P42127

O75882

1

binding

up-regulates

0.391

Attractin is a low-affinity receptor for agouti protein, but not agrp, in vitro and in vivo.

SIGNOR-85496

P15172

P15692

1

transcriptional regulation

up-regulates quantity by expression

0.391

We further demonstrate that the myogenic transcription factor, MyoD, and its heterodimeric binding proteins E12 and E47, up-regulate the expression of endogenous VEGF through direct interaction with the VEGF promoter.

SIGNOR-257598

Q9P1W9

Q92934

1

phosphorylation

down-regulates activity

0.391

All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death.

SIGNOR-249604

P48729

Q13501

1

phosphorylation

up-regulates activity

0.391

Mechanistically, CSNK1A1 interacted with STING1 upon the CGAS-STING1 pathway activation and promoted STING1 autophagic degradation by enhancing the phosphorylation of SQSTM1/p62 at serine 351 (serine 349 in human), which was critical for SQSTM1-mediated STING1 autophagic degradation.

SIGNOR-273769

P19484

Q9GZQ8

1

transcriptional regulation

up-regulates quantity by expression

0.391

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276559

Q8N726

Q13535

1

phosphorylation

up-regulates activity

0.391

Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressorInduction of ATR activity in Hs68 E2F1ER cells by endogenous ARF.

SIGNOR-134781

Q6GPH4

Q13489

1

binding

down-regulates

0.391

Immunoprecipitation studies indicate that xaf1 binds to xiap,birc2,birc3

SIGNOR-155288

Q12904

Q9HAU4

1

binding

up-regulates activity

0.391

Here, we report that AIMP1 negatively regulates TGF-_ signaling via stabilization of Smurf2.

SIGNOR-227470

Q99626

Q07654

1

transcriptional regulation

up-regulates quantity by expression

0.391

The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells.

SIGNOR-253967

P43405

P17252

1

phosphorylation

up-regulates activity

0.391

We present evidence that Tyr-662 and Tyr-658 of PKCbetaI and PKCalpha, respectively, are phosphorylated by Syk in the membrane compartment of FcepsilonRI-stimulated mast cells. These phosphorylations require prior PKC autophosphorylation of the adjacent serine residues (Ser-661 and Ser-657, respectively) and generate a binding site for the SH2 domain of the adaptor protein Grb-2.

SIGNOR-246581

Q9Y2X7

Q02750

1

binding

up-regulates activity

0.391

We found both MAT2B variants interact with GIT1. MAT2B directly promoted binding of GIT1 and ERK2 to MEK1. MAT2B and GIT1 interact and are overexpressed in most human liver and colon cancer specimens.

SIGNOR-261245

O95155

Q99689

1

polyubiquitination

up-regulates activity

0.391

E4B mediated the polyubiquitylation of FEZ1 but did not affect its intracellular stability, suggesting that such modification of FEZ1 is not a signal for its proteolysis. Polyubiquitylation of FEZ1 by E4B required Lys(27) of ubiquitin. Expression of a dominant-negative mutant of E4B in rat pheochromocytoma PC12 cells resulted in inhibition of neurite extension induced either by nerve growth factor or by coexpression of FEZ1 and constitutively active PKCzeta. These findings indicate that E4B serves as a ubiquitin ligase for FEZ1 and thereby regulates its function but not its degradation. The polyubiquitin chain attached by E4B to FEZ1 might therefore facilitate the interaction of FEZ1 with an unidentified target that functions in neuritogenesis.

SIGNOR-271510

Q8NG27

P84022

1

ubiquitination

down-regulates activity

0.391

In summary, these results indicated that PJA1 promotes the ubiquitination of phosphorylated SMAD3, resulting in reduced activity of a TGF-\u03b2/SMAD3/\u03b22SP-dependent tumor-suppressing pathway in HCC cells ( xref ).

SIGNOR-278832

P14416

P19086

1

binding

up-regulates activity

0.391

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-257096

Q9H4B4

Q07817

1

phosphorylation

up-regulates

0.391

Polo kinase 3 (plk3) was implicated in bcl-xl(ser49) phosphorylation. These data indicate that, during g2 checkpoint, phospho-bcl-xl(ser49) is another downstream target of plk3, acting to stabilize g2 arrest.

SIGNOR-172230

Q9UK99

Q9HCE7

1

binding

down-regulates quantity by destabilization

0.391

F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.

SIGNOR-272441

P42345

P06213

1

phosphorylation

up-regulates activity

0.391

Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR and InsR.

SIGNOR-280045

Q12923

P00519

1

dephosphorylation

down-regulates activity

0.39

We also found that PTPN13 dephosphorylates and inhibits c-Abl.|While the above results indicated that calpain-2 could cleave PTPN13 and that PTPN13 could dephosphorylate c-Abl at tyrosine 245, they did not determine whether calpain-2-mediated cleavage of PTPN13 resulted in its inactivation and increased tyrosine phosphorylation of c-Abl at tyrosine 245.

SIGNOR-277012

P23769

P01222

1

transcriptional regulation

up-regulates quantity by expression

0.39

Pit-1, is necessary but not sufficient to allow basal transcription of the mTSHβ gene.The analysis of the mTSHβ gene described in this report provides evidence for the participation of a zinc finger factor, GATA-2, with a POU homeodomain partner, Pit-1, on a such a composite element.In summary, we have shown the requirement for at least two different classes of transcription factors to regulate mTSHβ gene expression. Both GATA-2 and Pit-1 can bind independently to the P1 region of the promoter, form a heteromeric complex with DNA, and functionally synergize to activate TSHβ promoter activity.

SIGNOR-267253

P49593

Q13153

1

dephosphorylation

down-regulates activity

0.39

The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.

SIGNOR-248530

Q15796

Q02078

1

binding

up-regulates

0.39

Our studies indicate that smad2 and 4 (smad2/4) complexes cooperate with mef2 regulatory proteins in a gal4-based one-hybrid reporter gene assay.

SIGNOR-235846

Q9P275

P06748

1

deubiquitination

up-regulates quantity by stabilization

0.39

USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation.

SIGNOR-272290

P17252

P35368

1

phosphorylation

down-regulates activity

0.39

Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.

SIGNOR-248988

P31749

P49760

1

phosphorylation

up-regulates

0.39

Akt directly binds to and phosphorylates clk2 on serine 34 and threonine 127, in vitro and in vivo.Our results suggest that akt activation controls cell survival to ionizing radiation by phosphorylating clk2, revealing an important regulatory mechanism required for promoting cell surviva

SIGNOR-167340

P46934

O43597

1

polyubiquitination

down-regulates quantity by destabilization

0.39

Endogenous and overexpressed Nedd4 polyubiquitinate Spry2 via Lys(48) on ubiquitin and decrease its stability.

SIGNOR-271425

Q15386

O75155

1

ubiquitination

down-regulates quantity by destabilization

0.39

We show that KIAA10 indeed associates with 26 S proteasomes in mammalian cells but that this interaction is likely to depend on contacts with a subunit(s) besides S2/Rpn1. Most importantly, we provide strong evidence that TIP120B (TBP-interacting protein 120B (22)) is a specific substrate that is targeted for degradation in skeletal muscle through KIAA10-catalyzed polyubiquitination.

SIGNOR-271454

P49841

Q86YF9

1

phosphorylation

up-regulates activity

0.39

Phosphorylation of Dzip1 by GSK3\u03b2 Promotes the Release of Rab8 GDP from GDI2.

SIGNOR-278251

P68400

P35221

1

phosphorylation

down-regulates

0.39

We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.

SIGNOR-161847

P23469

P28482

1

dephosphorylation

down-regulates activity

0.39

The effect of PTP epsilon on ERKs is at least in part indirect because phosphorylation of the threonine residue in the ERK activation loop is reduced in the presence of PTP epsilon. Nonetheless, PTP epsilon is present in a molecular complex with ERK, providing PTP epsilon with opportunity to act on ERK proteins also directly. We conclude that PTP epsilon is a physiological inhibitor of ERK signaling|These enzymes are joined by the large family of dual-specificity phosphatases, which are structurally similar to tyrosine phosphatases but which can dephosphorylate both residues of the activation loop

SIGNOR-248448

P78317

P08047

1

polyubiquitination

down-regulates quantity by destabilization

0.39

Here, we identified RNF4 as the ubiquitin E3 ligase of Sp1. From in vitro and in vivo experiments, we found that sumoylated Sp1 can recruit RNF4 as a ubiquitin E3 ligase that subjects sumoylated Sp1 to proteasomal degradation.

SIGNOR-272720

P26441

O75462

1

binding

up-regulates

0.39

We recently demonstrated that cardiotrophin-like cytokine (clc) associates with the soluble orphan receptor cytokine-like factor-1 (clf) to form a heterodimeric cytokine that displayed activities only on cells expressing the tripartite cntf receptor on their surface

SIGNOR-106635

P19784

Q92769

1

phosphorylation

up-regulates activity

0.39

HDAC2 is phosphorylated uniquely by protein kinase CK2 in vitro. Studies using unfractionated cell extracts with CK2 inhibitors suggest that protein kinase CK2 is the major source of HDAC2 kinase. Finally, and perhaps most interesting, HDAC2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. | Since our data suggest that protein kinase CK2 is the major kinase responsible for HDAC2 phosphorylation, and because Ser422 and Ser424, but not Ser411, lie within CK2 recognition sequences, we believe that Ser394, Ser422, and Ser424 constitute the three phosphorylated residues in HDAC2.

SIGNOR-251001

Q96P31

P29350

1

binding

up-regulates activity

0.39

Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.

SIGNOR-274013

Q9UBF6

Q13794

1

ubiquitination

down-regulates activity

0.39

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271446

P31749

Q96IZ0

1

phosphorylation

down-regulates activity

0.39

Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy

SIGNOR-279668

Q00535

P12931

1

phosphorylation

up-regulates

0.39

These results present compelling evidence that cdk5/p35 kinase is responsible for the novel phosphorylation of c-src at ser75 in neuronal cells, raising the intriguing possibility that c-src acts as an effector of cdk5/p35 kinase during neuronal development.

SIGNOR-71950