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 |
|---|---|---|---|---|---|---|---|
Q15418 | O15530 | 0 | phosphorylation | up-regulates activity | 0.63 | Full-length RSK1, RSK2, and RSK3 Are Activated when Coexpressed with PDK1 in COS7 Cells. Ser221 phosphorylation is increased 2–3-fold during ERK-mediated activation of RSK1 in COS1 cells | SIGNOR-250270 |
P42261 | Q13555 | 0 | phosphorylation | up-regulates activity | 0.63 | In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. | This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity. | SIGNOR-250697 |
Q9UM47 | O00548 | 0 | binding | up-regulates | 0.63 | These results suggest that delta1, jagged1, and jagged2 are ligands for notch1 and notch3 receptors. | SIGNOR-82398 |
P98177 | Q00987 | 0 | ubiquitination | down-regulates activity | 0.63 | Mdm2 Induces Mono-Ubiquitination of FOXO4.|higher amounts of Mdm2 transfected resulted in reduced FOXO4 transcriptional activity. | SIGNOR-278656 |
Q9Y4K3 | Q8N2H9 | 0 | ubiquitination | down-regulates quantity | 0.63 | Finally, we used coexpression studies to directly demonstrate that Pellino3 inhibits the ability of wild-type TRAF6 to stabilize HIF-1alpha but not the stabilizing effects of the K124A TRAF6 mutant that is resistant to ubiquitination.|In the present study, Pellino3 ubiquitinates TRAF6 with lysine 63-linked polyubiquitin chains to block the interaction of TRAF6 with HIF-1\u03b1. | SIGNOR-278707 |
Q13469 | Q08209 | 0 | dephosphorylation | up-regulates activity | 0.629 | NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity | SIGNOR-248690 |
Q96FF9 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.629 | Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. | SIGNOR-276116 |
P45985 | Q9UPT6 | 0 | binding | up-regulates | 0.629 | Overexpression of full-length jsap1 in cos-7 cells led to a considerable enhancement of jnk3 activation, and modest enhancement of jnk1 and jnk2 activation, by the mekk1-sek1 pathwaythe regions of jsap1 that bound jnk, sek1, and mekk1 were distinct from one another. Jnk and mekk1 also bound jsap1 in vitro, suggesting that these interactions are direct. | SIGNOR-71468 |
P61586 | Q9UNA1 | 0 | gtpase-activating protein | down-regulates activity | 0.629 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260481 |
Q92558 | Q9UQB8 | 0 | binding | up-regulates | 0.629 | Here we demonstrate that irsp53, a substrate forinsulinreceptor with unknown function, is the 'missing link' between rac and wave. Activated rac binds to the amino terminus of irsp53, and carboxy-terminal src-homology-3 domain of irsp53 binds to wave to form a trimolecular complex. | SIGNOR-85299 |
O75558 | Q15833 | 0 | binding | up-regulates activity | 0.629 | Strikingly, addition of Munc18-2 substantially and selectively facilitates complete fusion mediated by lipid-anchored STX11 by promoting and stabilizing the assembly of SNARE complexes. | SIGNOR-261898 |
P09619 | P22681 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.629 | Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha. | SIGNOR-272549 |
P49815 | Q05086 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.629 | An in vivo ubiquitination assay was done to reveal that E6AP promoted the ubiquitination of TSC2 independent of HPV16 E6. We further found that TSC2 bound E6AP in the presence as well as in the absence of HPV16 E6. The binding regions on E6AP and TSC2 have been identified as amino acid (aa) 260-316, aa 428-500 and aa 1-175, aa 1251-1807, respectively. Taken together, degradation of TSC2 is mediated by E6AP ubiquitin ligase. | SIGNOR-271396 |
O60503 | P63092 | 0 | binding | up-regulates activity | 0.628 | Adenylyl cyclase 9 (AC9) is a membrane-bound enzyme that converts ATP into cAMP. The enzyme is weakly activated by forskolin, fully activated by the G protein Gαs subunit and is autoinhibited by the AC9 C-terminus. | SIGNOR-278883 |
Q9UKV3 | P42574 | 0 | cleavage | up-regulates | 0.628 | Induces apoptotic chromatin condensation after activation by casp3 | SIGNOR-70800 |
P15884 | P41134 | 0 | binding | down-regulates activity | 0.628 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241385 |
O43353 | P98170 | 0 | ubiquitination | up-regulates activity | 0.628 | XIAP is the essential E3 for RIPK2 ubiquitination and interacts with RIPK2 through its baculoviral IAP-repeat (BIR). | SIGNOR-280449 |
P06730 | O00571 | 0 | binding | down-regulates activity | 0.628 | DDX3 is a human RNA helicase with plethoric functions. we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G. | SIGNOR-269193 |
P17655 | P28482 | 0 | phosphorylation | up-regulates | 0.628 | Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo. | SIGNOR-123079 |
P15056 | P28482 | 0 | phosphorylation | down-regulates activity | 0.628 | Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. | SIGNOR-236388 |
Q9NPG1 | Q9Y6F9 | 0 | binding | up-regulates | 0.628 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131891 |
P04626 | P15514 | 0 | phosphorylation | up-regulates | 0.628 | Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor | SIGNOR-31199 |
P23458 | Q9HBE5 | 0 | binding | up-regulates | 0.628 | Retroviral-mediated transduction of wild-type gamma c into xscid jt cells restored function to the il-21r, as shown by il-21-induced tyrosine phosphorylation of jak1 and jak3, and downstream activation of stat5 | SIGNOR-90266 |
P04637 | P53779 | 0 | phosphorylation | up-regulates | 0.628 | The targets of jnk include the transcription factors p53. P75ntr-mediated apoptosis was shown to be dependent of p53 | SIGNOR-120552 |
P27986 | P03372 | 0 | binding | up-regulates | 0.628 | Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k. | SIGNOR-140470 |
Q9NPG1 | P04628 | 0 | binding | up-regulates activity | 0.628 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131571 |
P61586 | Q5T5U3 | 0 | gtpase-activating protein | down-regulates activity | 0.628 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260475 |
P54646 | Q15831 | 0 | phosphorylation | up-regulates | 0.627 | We demonstrated that lkb1 phosphorylates ampk on the activation loop threonine (thr172) within the catalytic subunit and activates ampk in vitro. Here, we have investigated whether lkb1 corresponds to the major ampkk activity present in cell extracts. Ampkk purified from rat liver corresponds to lkb1, and blocking lkb1 activity in cells abolishes ampk activation in response to different stimuli | SIGNOR-122725 |
P46527 | Q12778 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.627 | To date , we have found that TNC regulates the transcriptional activity of FOXO1. And p27Kip1 is one of the transcriptional targets of FOXO1 (Fig. 5A). We speculated that TNC could regulate the binding of FOXO1 to the CDKN1B promoter. | SIGNOR-277739 |
P46531 | O00548 | 0 | binding | up-regulates activity | 0.627 | Notch signaling is a highly conserved pathway involved in cell fate choice during development with Delta and Jagged constituting the two evolutionary conserved families of Notch ligands. These ligands are transmembrane proteins with conserved biochemical structure that share their receptors and signal through a common mechanism. Upon ligand binding Notch receptors are proteoliticaly cleaved, the intracellular domain of Notch (NICD) is released and translocated to the nucleus, where it activates target genes. In mammals, four receptors and five ligands have been described. Delta-1, Delta-3 and Delta-4 are homologues to Drosophila Delta and Jagged-1 and Jagged-2 to Drosophila Serrate. | SIGNOR-209732 |
P04626 | Q9UNE7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.627 | The ErbB2 kinase domain is required for GA-induced and CHIP-dependent ErbB2 ubiquitination and degradation . | SIGNOR-278645 |
P61244 | Q16539 | 0 | phosphorylation | down-regulates | 0.627 | Mxi2 phosphorylates max both in vitro and in vivo. Phosphorylation by mxi2 may affect the ability of max to oligomerize with itself and its partners, bind dna, or regulate gene expression. | SIGNOR-26511 |
P30304 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.627 | Expression of Cdc25A is transcriptionally regulated by Myc and E2F-1 , both of which are expressed in MCF-7 cells in response to estrogen | SIGNOR-245465 |
P40189 | Q16619 | 0 | binding | up-regulates | 0.627 | In the cos-7 cell line demonstrate that gp130-gp190 heterocomplex formation is essential for ct-1 signaling | SIGNOR-46509 |
Q08828 | P63092 | 0 | binding | up-regulates activity | 0.627 | Because adenylyl cyclases are directly activated by G(s)alpha and the carboxyl termini of the various Galpha proteins determine their receptor coupling specificity, we proposed a set of chimeric G(s)alpha where the COOH-terminal five amino acids are replaced by those of other Galpha proteins and used these to dissect the potential Galpha linked to a given GPCR | SIGNOR-156958 |
Q8IVP5 | Q96HS1 | 0 | dephosphorylation | up-regulates activity | 0.627 | Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation. | SIGNOR-273654 |
P61956 | Q6ZNA4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.626 | Arkadia ubiquitinates poly-SUMO2 chains in a SIM- and RING-dependent manner. | SIGNOR-272882 |
P27986 | Q6ZUJ8 | 0 | binding | up-regulates | 0.626 | Bcap is constitutively phosphorylated and associated with the p85 subunit of pi3k in macrophages. Tlr signaling causes the phosphorylation of the small amount of bcap that is associated with membranes in the resting state or the translocation of phosphorylated bcap from the cytoplasm to the membrane. This accumulation of tyrosine-phosphorylated bcap at the membrane with its associated pi3k would then allow for the catalysis of ptd ins p2 to ptd ins p3 and downstream pi3k-dependent signals. Bcap is an essential activator of the pi3k pathway downstream of tlr signaling | SIGNOR-191673 |
P46108 | P29320 | 0 | binding | up-regulates | 0.626 | Our results suggest that recruitment of crkii and activation of rho signalling are responsible for epha3-mediated cell rounding, blebbing and de-adhesion, and that ephrin-a5-mediated receptor clustering and epha3 tyrosine kinase activity are essential for this response | SIGNOR-115335 |
P35222 | P48730 | 0 | phosphorylation | down-regulates | 0.626 | However, ckiepsilon has been recently shown to interact with axin (sakanaka et al. 1999;rubinfeld et al. 2001), and it was proposed that this kinase mediates axin-induced apc phosphorylation, thereby stabilizing the -catenin degradation complex (rubinfeld et al. 2001). We have, therefore, evaluated cki as a candidate s45-kinase in several assays, both in vitro and in vivo. | SIGNOR-87441 |
Q96MS0 | O94813 | 0 | binding | up-regulates activity | 0.626 | This observation suggests that Slit2 may require the Robo2 and Robo3 receptors in this process . Slit2 causes the miRNA miR-182 to release cofilin1 mRNA, potentiating cofilin1 local translation and resulting in growth cone collapse. The use of morpholinos or RNAi to knockdown robo2 and robo3 in X. laevis RGCs, would be useful to further confirm that Robo2 and Robo3 are the receptors involved in Slit2-dependent cofilin1 translation. | SIGNOR-268381 |
P51668 | O00623 | 0 | binding | up-regulates activity | 0.626 | Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle. | SIGNOR-253024 |
Q08209 | P0DP25 | 0 | binding | up-regulates | 0.626 | Calcium-bound calmodulin associates with calcineurin (cn), releasing the phosphatase from the repressive effects on an autoinhibitory domain. | SIGNOR-266343 |
P46782 | O00566 | 0 | binding | up-regulates activity | 0.626 | Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome. | SIGNOR-261175 |
Q9HBY0 | P14598 | 0 | binding | up-regulates activity | 0.626 | Stimulus-induced phosphorylation of p47phox causes a conformational change, by which both PX and SH3 domains become accessible to their membranous targets, phosphoinositides and p22phox, respectively. Cooperation of these two interactions, each being indispensable, enables p47phox to form a stable complex with cytochrome b558 (composed of the two subunit gp91phox and p22phox), leading to activation of the phagocyte NADPH oxidase. | SIGNOR-276624 |
Q13485 | P63279 | 0 | sumoylation | up-regulates | 0.626 | The mh1 domain of smad4 was shown to associate physically with ubc9, the ubiquitin carrier protein (e2) conjugating enzyme in sumoylation. In cultured cells, smad4 is modified by sumo-1 at the endogenous level. The sumoylation sites were identified as two evolutionarily conserved lysine residues, lys-113 and lys-159, in the mh1 domain. We found that the mutations at lys-113 and lys-159 did not alter the ability of smad4 to form a complex with smad2 and fast on the mix.2 promoter. Importantly, sumo-1 overexpression enhanced tgf-beta-induced transcriptional responses. These findings identify sumoylation as a unique mechanism to modulate smad4-dependent cellular responses | SIGNOR-98997 |
P45985 | Q16584 | 0 | phosphorylation | up-regulates | 0.625 | These data suggest that mlk-3 phosphorylates sek1 directly and that it does so specifically on those residues known to activate sek1 in vivo. | SIGNOR-75836 |
P63104 | P49137 | 0 | phosphorylation | down-regulates activity | 0.625 | We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. | SIGNOR-250151 |
P00533 | P12931 | 0 | phosphorylation | up-regulates activity | 0.625 | Revealed that peptides derived from egfr residues y992, y1086, y1101, and y1148 bound directly to the sh2 domain of c-src (figure 8c). These experiments demonstrate that a specific subset of egfr receptor c-src phosphorylation sites are also ligands for the sh2 domain of c-src.Cellular src functions as a co-transducer of transmembrane signals emanating from a variety of growth factor receptors, including egfr | SIGNOR-44251 |
P63096 | Q9HBW0 | 0 | binding | up-regulates | 0.625 | Lysophosphatidic acid (lpa), a major g protein coupled receptor (gpcr)-activating ligand present in serum, elicits growth factor like responses by stimulating specific gpcrs coupled to heterotrimeric g proteins such as g(i), g(q), and g12/13. lpa2 also can couple to the gi/o, g12/13, and gqfamilies. | SIGNOR-84559 |
O00238 | Q13873 | 0 | binding | up-regulates | 0.625 | Using several complementary approaches, we investigated the formation of homomeric and heteromeric complexes between the two known bmp type i receptors (br-ia and br-ib) and the bmp type ii receptor (br-ii). | SIGNOR-75655 |
P20339 | Q92696 | 0 | lipidation | up-regulates activity | 0.625 | Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional | SIGNOR-265572 |
P03372 | Q16539 | 0 | phosphorylation | up-regulates | 0.625 | Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells | SIGNOR-136950 |
Q12860 | P78357 | 0 | relocalization | up-regulates activity | 0.625 | These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr. | SIGNOR-269073 |
P46531 | Q9Y219 | 0 | binding | up-regulates | 0.625 | Immunohistochemistry revealed coexpression of jagged2 and notch1 within thymus and other fetal murine tissues, consistent with interaction of the two proteins in vivo. Coculture of fibroblasts expressing human jagged2 with murine c2c12 myoblasts inhibited myogenic differentiation, accompanied by increased notch1 and the appearance of a novel 115-kda notch1 fragment. Exposure of c2c12 cells to jagged2 led to increased amounts of notch mrna as well as mrnas for a second notch receptor, notch3, and a second notch ligand, jagged1. Constitutively active forms of notchl in c2c12 cells also induced increased levels of the same set of mrnas, suggesting positive feedback control of these genes initiated by binding of jagged2 to notch1. | SIGNOR-236922 |
Q16611 | Q07820 | 0 | binding | down-regulates | 0.625 | Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax | SIGNOR-149774 |
Q13705 | O95390 | 0 | binding | up-regulates | 0.625 | Here we demonstrate using genetic and biochemical studies that actriib and its subfamily receptor, actriia, cooperatively mediate the gdf11 signal in patterning the axial vertebrae, and that gdf11 binds to both actriia and actriib, and induces phosphorylation of smad2 | SIGNOR-95309 |
O75581 | Q9H1J7 | 0 | binding | up-regulates | 0.625 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131888 |
Q9UJW0 | Q01484 | 0 | relocalization | up-regulates quantity | 0.625 | We present evidence for an ankyrin-based mechanism for sarcolemmal localization of dystrophin and beta-DG. Ankyrin-B thus is an adaptor required for sarcolemmal localization of dystrophin, as well as dynactin-4. | SIGNOR-266713 |
P08138 | P22694 | 0 | phosphorylation | up-regulates | 0.625 | Pka phosphorylates the p75 receptor and regulates its localization to lipid rafts. activation of camp?PKA Is required for translocation of p75ntr to lipid rafts, and for biochemical and biological activities of p75ntr, such as inactivation of rho and the neurite outgrowth. | SIGNOR-99755 |
Q9NPG1 | Q93098 | 0 | binding | up-regulates | 0.625 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132024 |
O00463 | Q92956 | 0 | binding | up-regulates activity | 0.625 | ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5|synergistic activation of NF-κB by ATAR and TRAF5 293 cells | SIGNOR-262592 |
Q9UN19 | P07948 | 0 | phosphorylation | up-regulates activity | 0.625 | Src family kinases mediate receptor-stimulated, phosphoinositide 3-kinase-dependent, tyrosine phosphorylation of dual adaptor for phosphotyrosine and 3-phosphoinositides-1 in endothelial and B cell lines|yrosine phosphorylation of DAPP-1 appears important for appropriate intracellular targeting and creates a potential binding site for Src homology 2 domain-containing proteins. | SIGNOR-249378 |
Q9Y3E7 | Q9UN37 | 0 | cleavage | up-regulates activity | 0.625 | Here, we show, using high-speed atomic force microscopy and electron microscopy, that the AAA-type adenosine triphosphatase VPS4 constricts and cleaves ESCRT-III CHMP2A-CHMP3 helical filaments in vitro. Our results demonstrate that VPS4 actively constricts ESCRT-III filaments and cleaves them before their complete disassembly. We propose that the formation of ESCRT-III dome-like end caps by VPS4 within a membrane neck structure constricts the membrane to set the stage for membrane fission. | SIGNOR-260847 |
Q9UM47 | Q9Y219 | 0 | binding | up-regulates | 0.625 | These results suggest that delta1, jagged1, and jagged2 are ligands for notch1 and notch3 receptors. | SIGNOR-82401 |
P61586 | O14640 | 0 | binding | up-regulates activity | 0.624 | Although there are other activators of PCP, Wnt5a can activate the PCP pathway by forming a complex with Fzd and Ror2 receptors, activating DVL, which in turn activates Rho-family small GTPases, including RhoA and Rac, and their downstream effectors, Rho-associated protein kinase (ROCK), the actin-binding protein, Filamin A and c-Jun N-terminal protein kinase (JNK) | SIGNOR-258971 |
Q9P104 | P07949 | 0 | binding | up-regulates | 0.624 | Dok-4 and dok-5 enhance c-ret-dependent activation of mitogen-activated protein kinase | SIGNOR-109516 |
P25116 | P00747 | 0 | cleavage | down-regulates activity | 0.624 | Plasmin mediates the lysis of fibrin clots and could in different studies activate platelets or inhibit the responses induced by thrombin (41-43). Our study favors a net inactivating effect on PAR1 despite minor cleavage at Arg41, on the basis of preferential cleavage at positions Arg70 and Lys76, COOH-terminal to the Arg41-Ser42 activation site. | SIGNOR-263572 |
Q08050 | P11802 | 0 | phosphorylation | up-regulates | 0.624 | We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence. | SIGNOR-177266 |
P53990 | Q6PHR2 | 0 | phosphorylation | down-regulates activity | 0.624 | ULK3 phosphorylation of IST1 is required to sustain the abscission checkpoint and inhibits IST1 function in abscission. | SIGNOR-278205 |
O14950 | Q13464 | 0 | phosphorylation | up-regulates | 0.624 | Here we found that rho-kinase has an activity for mrlc diphosphorylation at both threonine 18 and serine 19 in nonmuscle cells using sequential column chromatographies. | SIGNOR-91542 |
Q6IQ22 | A2RUS2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.624 | ULK-mediated phosphorylation of the guanine nucleotide exchange factor DENND3 at serines 554 and 572 upregulates its GEF activity toward the small GTPase Rab12.|active Rab12 facilitates autophagosome trafficking, thus establishing a crucial role for the ULK/DENND3/Rab12 axis in starvation-induced autophagy. | SIGNOR-264734 |
P37840 | Q5S007 | 0 | phosphorylation | down-regulates activity | 0.624 | Here we show that full-length Lrrk2 or fragments containing its kinase domain have a significant capacity to phosphorylate recombinant alpha synuclein (Asyn) at serine 129. Such phosphorylated Asyn is the major component of pathological deposits in PD. | SIGNOR-249690 |
Q14289 | P12931 | 0 | phosphorylation | up-regulates | 0.624 | These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity. | SIGNOR-133870 |
Q99459 | P06493 | 0 | phosphorylation | up-regulates activity | 0.624 | Cdc5-dependent Net1 phosphorylation and Cdc14 release from the nucleolus require prior Cdc5 activation by Cdk1 and active separase to promote Cdc14 activation.|Cdk1 initially phosphorylates Cdc5, mostly at T242 and T238 (T242 phosphorylation is especially relevant based on our results), and phosphorylation activates its kinase activity, which is essential for anaphase progression. | SIGNOR-279597 |
O60674 | P24394 | 0 | phosphorylation | up-regulates activity | 0.624 | Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6. | SIGNOR-249530 |
P03372 | P06401 | 0 | binding | up-regulates | 0.624 | Here we identify two domains of prb, erid-i and -ii, mediating a direct interaction with the ligand-binding domain of eralpha. | SIGNOR-98807 |
P04150 | P28482 | 0 | phosphorylation | down-regulates activity | 0.623 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action. | SIGNOR-249428 |
Q9ULL4 | Q13591 | 0 | binding | up-regulates activity | 0.623 | Plexin-B3 is a functional receptor for semaphorin 5A. Here we show that plexin-B3 is a high-affinity receptor specific for Sema5A. We further demonstrate that plexin-B3 activation by Sema5A mediates functional responses in plexin-B3-expressing cells (either fibroblasts, epithelial and primary endothelial cells). | SIGNOR-268373 |
Q9NPG1 | Q9GZT5 | 0 | binding | up-regulates | 0.623 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131616 |
P84022 | P27361 | 0 | phosphorylation | down-regulates | 0.623 | These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3. | SIGNOR-66781 |
P46531 | P25490 | 0 | binding | down-regulates activity | 0.623 | Taken together, these results indicate that transcription factor YY1 may modulate Notch signaling via association with the high molecular weight Notch complex [..] both YY1 and N1IC were present in a large complex of the nucleus to suppress the luciferase reporter activity transactivated by Notch signaling. | SIGNOR-251654 |
P49841 | P31751 | 0 | phosphorylation | down-regulates activity | 0.623 | Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1 | SIGNOR-245420 |
P20908 | P13497 | 0 | cleavage | up-regulates activity | 0.623 | BMP-1 Can Efficiently Cleave Pro-α1(V) N-propeptides and Pro-α2(V) C-propeptides and Less Efficiently Cleave Pro-α1(V) C-propeptides in Vitro.NH2-terminal sequencing of an ∼35-kDa band in the BMP-1-treated material (N-α1(V), Fig. 3 B,lanes 2 and 3) showed it to correspond to the NH2-terminal portion of the pro-α1(V) N-propeptide previously shown to be cleaved in pro-α1(V)3 homotrimers by BMP-1 (39), whereas NH2-terminal sequencing of an ∼38-kDa band (C-α1(V)BMP-1, Fig. 3 B,lanes 2 and 3) showed it to correspond to pro-α1(V) C-propeptides cleaved between Asp-1594 and Asp-1595. | SIGNOR-256344 |
Q9NVI1 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.623 | Alternatively, the locally accumulated ATRIP-ATR might have sufficient activity to phosphorylate FANCI without TOPBP1 stimulation.|The results described above and our previous studies clearly indicated that FANCI phosphorylation is mediated by ATR kinase in a manner dependent on the FA core complex and FANCD2 protein. | SIGNOR-279320 |
Q9NPG1 | O14905 | 0 | binding | up-regulates | 0.623 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132111 |
P63000 | Q15052 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.623 | ARHGEF6 is a Rho guanine nucleotide exchange factor for Rac1 and constitutively bound to GIT1. NO and PGI2 activate PKG and PKA, respectively and both kinases phosphorylate ARHGEF6 on Ser-684 and possibly on Ser-640. Phosphorylation of ARHGEF6 results in the assembly of a GIT1-ARHGEF6–14-3-3 complex. These changes might contribute to PGI2- and NO-mediated Rac1 inhibition. | SIGNOR-272167 |
P08151 | P49757 | 0 | binding | down-regulates | 0.623 | The consequent activation of_ itch, together with the recruitment of gli1 through direct binding with_ numb, allows gli1 to enter into the complex, resulting in gli1 ubiquitination and degradation. | SIGNOR-167841 |
Q14344 | P35348 | 0 | binding | up-regulates activity | 0.623 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257279 |
O95835 | Q13043 | 0 | phosphorylation | up-regulates | 0.623 | We show that Mst2 and hWW45 interact with each other in human cells and that both Mst2 and Mst1 are able to phosphorylate Lats1 and Lats2, thereby stimulating Lats kinase activity. | SIGNOR-133551 |
P61371 | Q9UBR4 | 0 | binding | up-regulates activity | 0.623 | The Lhx3-Isl1 C terminus interaction was dependent on the LIM domains of Lhx3. The combinatorial expression of the LIM homeodomain proteins Isl1, Isl2, Lhx1, and Lhx3 in subsets of developing motor neurons correlates with the future organization of these neurons into motor columns with distinct innervation targets, implying a functional role for LIM homeodomain protein combinations in the specification of neuronal identity | SIGNOR-220169 |
P27986 | P06239 | 0 | phosphorylation | down-regulates activity | 0.623 | the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85. | SIGNOR-251383 |
P04626 | O60674 | 0 | phosphorylation | up-regulates activity | 0.623 | Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. | SIGNOR-279197 |
P21854 | P29350 | 0 | dephosphorylation | down-regulates | 0.623 | Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals. | SIGNOR-60155 |
Q16539 | Q05923 | 0 | dephosphorylation | down-regulates | 0.623 | We show that the in vivo substrate specificities of individual phosphatases are unique. Pac1, mkp-2, and mkp-1 recognize erk and p38, erk and jnk, and erk, p38, and jnk, respectively | SIGNOR-40918 |
P28749 | P67775 | 0 | dephosphorylation | up-regulates | 0.623 | Pocket protein family consists of the retinoblastoma tumor suppressor protein (prb) and the functionally and structurally related proteins p107 and p130./dephosphorylation of p130 and p107 in cell extracts is inhibited by concentrations of okadaic acid known to inhibit pp2a, but not pp1. Finally, the pp2a catalytic subunit pp2a/c) specifically interacts with both p130 and p107 / the cell cycle repressor activity of pocket proteins is inactivated by cdk mediated phosphorylation. | SIGNOR-129749 |
P14859 | Q16633 | 0 | binding | up-regulates | 0.622 | Obf1 enhances transcriptional potential of oct1. | SIGNOR-100968 |
P84022 | P35813 | 0 | dephosphorylation | down-regulates activity | 0.622 | Ppm1a dephosphorylates and promotes nuclear export of tgfbeta-activated smad2/3; these results suggest that phospho-smad2 is a direct substrate of mg2+-dependent ppm1a. in conclusion, ppm1a is a bona fide phosphatase that directly dephosphorylates the critical sxs motif of r-smads. | SIGNOR-232110 |
O95644 | Q16539 | 0 | phosphorylation | down-regulates | 0.622 | We show that jnk, erk, and p38 physically associate with the nfatc n-terminal regulatory domain and can directly phosphorylate functionally important residues involved in regulating nfatc subcellular localization, namely ser(172) and the conserved nfatc ser-pro repeats. | SIGNOR-74560 |
P84022 | P50750 | 0 | phosphorylation | down-regulates activity | 0.622 | Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3. | SIGNOR-161589 |
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