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 |
|---|---|---|---|---|---|---|---|
P63092 | Q13258 | 0 | binding | up-regulates activity | 0.593 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256755 |
Q9UM47 | P00533 | 0 | phosphorylation | up-regulates activity | 0.593 | Here, we report that treatment of EGFR mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem like cells through EGFR dependent activation of Notch3.|We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. | SIGNOR-280002 |
Q9H1A4 | P06493 | 0 | phosphorylation | up-regulates | 0.592 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation | SIGNOR-119705 |
Q08722 | P35442 | 0 | binding | up-regulates | 0.592 | We report here that iap is a receptor for the ts1 cbd and its vvm-containing peptides and that a function-blocking anti-iap mab inhibits the chemotactic response to ts1 and its cbd peptides in endothelial cells. | SIGNOR-39749 |
Q92730 | Q14451 | 0 | binding | up-regulates | 0.592 | We would like to propose that when cells are driven to divide by growth factor stimulation, grb7 relocalizes at the membrane, in the same subcellular compartment as rnd1, where they could interact in vivo. | SIGNOR-74914 |
P05787 | Q16539 | 0 | phosphorylation | up-regulates | 0.592 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif ((68)nqsllspl) and becomes phosphorylated in cultured cells and organs during mitosis, cell stress, and apoptosis. Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase.The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114079 |
P35222 | Q06945 | 0 | binding | up-regulates activity | 0.592 | We have demonstrated that Sox17 and Sox4 can directly interact with β-catenin and TCF/LEF proteins.Sox4 enhances β-catenin/TCF activity and the proliferation of SW480 cells.In contrast, Sox4 may function to stabilize β-catenin protein. | SIGNOR-256138 |
P41968 | O00253 | 0 | binding | down-regulates activity | 0.592 | AGRP is a potent antagonist of the melanocortin-3 receptor and the MC4R and has also been shown to have a lesser degree of inhibitory action at the melanocortin-5 receptor. | SIGNOR-252380 |
P01137 | P14780 | 0 | cleavage | up-regulates | 0.592 | We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-_ (tgf-_), which constitutes a novel mechanism of tgf-_ activation. | SIGNOR-74461 |
Q9Y4H2 | P24394 | 0 | phosphorylation | up-regulates | 0.592 | Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2. | SIGNOR-100771 |
Q9GZY6 | P43405 | 0 | phosphorylation | up-regulates activity | 0.592 | Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases. | SIGNOR-273576 |
P48058 | Q9UQM7 | 0 | phosphorylation | up-regulates | 0.592 | Receptor internalization, altered;intracellular localization | SIGNOR-97546 |
P05412 | P68400 | 0 | phosphorylation | down-regulates | 0.592 | Casein kinase ii is a negative regulator of c-jun dna binding and ap-1 activitywe show that two of these sites, thr-231 and ser-249, are phosphorylated by casein kinase ii (ckii). | SIGNOR-19607 |
O14777 | P51955 | 0 | phosphorylation | up-regulates | 0.592 | Phosphorylation of the mitotic regulator protein hec1 by nek2 kinase is essential for faithful chromosome segregation.Hec1 (highly expressed in cancer) plays essential roles in chromosome segregation by interacting through its coiled-coil domains with several proteins that modulate the g(2)/m phase.Nek2 phosphorylates hec1 on serine residue 165, both in vitro and in vivo. | SIGNOR-94322 |
P33991 | P06493 | 0 | phosphorylation | down-regulates activity | 0.592 | We report here that human mcm4, a subunit of the putative dna replicative helicase, is extensively phosphorylated in hela cells when they are incubated in the presence of inhibitors of dna synthesis or are exposed to uv irradiation. The data presented here indicate that the consecutive actions of atr-chk1 and cdk2 kinases are involved in this phosphorylation in the presence of hydroxyurea. Phosphorylation of t19 correlates with lowered level of dna helicase activity of the purified mcm4,6,7 complex. | SIGNOR-100877 |
P04637 | Q9NYY3 | 0 | phosphorylation | up-regulates activity | 0.592 | Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. | SIGNOR-278980 |
P04049 | P67775 | 0 | dephosphorylation | up-regulates | 0.592 | Both pp2a holoenzymes were found to associate with raf1 and catalyze dephosphorylation of inhibitory phospho-ser-259. Together these findings indicate that pp2a abalphac and abdeltac holoenzymes function as positive regulators of raf1-mek1/2-erk1/2 signaling by targeting raf1. | SIGNOR-141170 |
Q13873 | Q6KF10 | 0 | binding | up-regulates | 0.592 | We found that transfection of small hairpin rna for bmprii and actriia in mc3t3 cells suppressed the signaling of gdf6, gdf7, and bmp10. Thus, the present approach provides a genomic paradigm for matching paralogous polypeptide ligands with a limited number of evolutionarily related receptors capable of activating specific downstream smad proteins. | SIGNOR-139093 |
P06239 | P43405 | 0 | phosphorylation | down-regulates activity | 0.592 | Our experiments indicate that the TCR-induced activation of Erk2 depends on the function of SH2 domain of Lck and is reduced by phosphorylation of wild type Lck at Tyr192 or by mutation of this site to a negatively charged amino acid. Such dependence on the SH2 domain has also been reported for the bulk of TCR-induced tyrosine phosphorylation and activation of the interleukin 2 gene (26). Thus, phosphorylation of Lck at Tyr192 may represent a negative feedback mechanism in the interplay between Src and Syk family PTKs in TCR signaling | SIGNOR-246562 |
O60664 | P51151 | 0 | null | up-regulates activity | 0.591 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253089 |
P36873 | Q9UD71 | 0 | binding | down-regulates activity | 0.591 | DARPP-32 (dopamine and cyclic AMP-regulated phospho-protein, relative molecular mass 32,000) is converted into an inhibitor of protein phosphatase 1 when it is phosphorylated by protein kinase A (PKA) at threonine 34.‚ | SIGNOR-264958 |
Q99075 | P78536 | 0 | cleavage | up-regulates activity | 0.591 | ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF | SIGNOR-259844 |
Q16539 | P45985 | 0 | phosphorylation | up-regulates activity | 0.591 | Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. | SIGNOR-34121 |
P63000 | O60890 | 0 | gtpase-activating protein | up-regulates activity | 0.591 | OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro | SIGNOR-268399 |
Q9Y297 | Q9UKB1 | 0 | binding | down-regulates quantity by destabilization | 0.591 | Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1. | SIGNOR-277476 |
Q13485 | Q8TAD8 | 0 | binding | down-regulates | 0.591 | In this study, we characterize a novel nuclear protein, termed snip1 its principal mechanism of action appears to be through transcription by binding to cbp/p300 and interfering with the ability of these coactivators to interact with smad4 | SIGNOR-78984 |
Q16539 | Q13202 | 0 | dephosphorylation | down-regulates | 0.591 | M3/6 (dusp8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of jnk and, to a lesser extent, p38 mapk | SIGNOR-199695 |
Q99062 | P04141 | 0 | binding | up-regulates | 0.591 | A g-csfr expression plasmid was introduced into interleukin-3 (il-3)-dependent mouse myeloid precursor fdc-p1 cells that normally do not respond to g-csf. G-csf stimulated proliferation of the transformants these results suggested that the g-csfr, but not the il-3/gm-csf receptors, transduced the neutrophilic differentiation signal into cells. | SIGNOR-31963 |
P21860 | O14944 | 0 | binding | up-regulates | 0.591 | For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4 | SIGNOR-191785 |
P04637 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.59 | Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage| Furthermore, in vitro phosphatase assays show that PP2A dephosphorylates p53 at S37. | SIGNOR-248619 |
Q12968 | P48729 | 0 | phosphorylation | down-regulates activity | 0.59 | Dominant-negative cki alpha Induces nuclear import of nf-at4 these results demonstrated that the cki alpha Phosphorylation sites identified in vitro were also specifically phosphorylated by cki alpha In vivo, and that these residues were crucial for the masking of the nls of nf-at4. | SIGNOR-109781 |
P19174 | P00519 | 0 | phosphorylation | down-regulates activity | 0.59 | C-Abl induces Tyr phosphorylation of PLC-γ1 in vivo. These findings demonstrate that c-Abl phosphorylates PLC-γ1 in vivo predominantly at Tyr 771 and Tyr 1003.c-Abl phosphorylation of PLC-γ1 causes downregulation of PLC activity. | SIGNOR-276001 |
Q14344 | O95136 | 0 | binding | up-regulates activity | 0.59 | 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-257401 |
P03372 | P00533 | 0 | phosphorylation | up-regulates | 0.59 | Activation of estrogen receptor-alpha (eralpha) by growth factors in the absence of estrogen is a well-documented phenomenon.Egfr tyrosine kinase in vitro stimulated the phosphorylation of recombinant er | SIGNOR-115734 |
Q9ULK5 | Q01974 | 0 | phosphorylation | down-regulates activity | 0.59 | In support of this, ror2 mutants abolish Vangl2 activity gradient and localization, and ror2; vangl2 double mutants phenocopy the wnt5a limb phenotype (Gao et al., 2011).4.6.|This process is mediated by its receptor Ror2, which in turn phosphorylates Vangl2 and induces asymmetric localization of Vangl2, propagating an activity gradient of Vangl2 in the proximal direction (Gao et al., 2011). | SIGNOR-280111 |
O75197 | O00755 | 0 | binding | up-regulates activity | 0.59 | 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-131900 |
O96017 | P78527 | 0 | phosphorylation | up-regulates | 0.59 | We have found that dna-pk is the major constituent of an activity present in extracts of mammalian cells that phosphorylates chk2. Our results suggest that hypophosphorylated chk2 can be phosphorylated at thr68 by dna-pk in vitro. | SIGNOR-133384 |
Q9UNE7 | Q9UK22 | 0 | binding | up-regulates activity | 0.59 | Through this novel interaction, which is mediated by the TPR domain of CHIP and an N-terminal PEST domain of Fbx2, CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins. This study highlights a novel mechanism of F-box protein-mediated ubiquitination that contributes to glycoprotein homeostasis. | SIGNOR-271589 |
O15111 | Q8IUD2 | 0 | binding | up-regulates | 0.59 | Elks likely functions by recruiting ikappabalpha to the ikk complex and thus serves a regulatory function for ikk activation. | SIGNOR-126430 |
O60462 | Q13214 | 0 | binding | up-regulates activity | 0.59 | Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction. | SIGNOR-261816 |
P50148 | P46663 | 0 | binding | up-regulates activity | 0.589 | 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-257304 |
P62753 | Q15418 | 0 | phosphorylation | up-regulates | 0.589 | We demonstrate that while ribosomal s6 kinase 1 (s6k1) phosphorylates rps6 at all sites, rsk exclusively phosphorylates rps6 at ser(235/236) in vitro and in vivo using an mtor-independent mechanism. | SIGNOR-153622 |
P63000 | Q17R89 | 0 | gtpase-activating protein | down-regulates activity | 0.589 | 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-260498 |
P42224 | Q05655 | 0 | phosphorylation | up-regulates | 0.589 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154791 |
P19838 | Q9Y297 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.589 | Here we demonstrate that following IkappaB kinase (IkappaK)-mediated phosphorylation, the C-terminal domain of p105 (residues 918-934) serves as a recognition motif for the SCF(beta)(-TrCP) ubiquitin ligase.In vitro, SCF(beta)(-TrCP) specifically conjugates and promotes processing of phosphorylated p105. | SIGNOR-272570 |
Q06187 | P43405 | 0 | phosphorylation | up-regulates activity | 0.589 | We have demonstrated that BLNK mediates Syk-dependent Btk activation. In a reconstitution cell system, coexpression of BLNK allows Syk to phosphorylate Btk on its tyrosine 551, leading to the enhancement of Btk activity. | SIGNOR-247586 |
Q03167 | P05111 | 0 | binding | down-regulates | 0.589 | Type iii tgf-beta receptor, betaglycan, can function as an inhibin co-receptor with actrii. Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing actrii and betaglycan. ability of betaglycan to facilitate inhibin antagonism of activin | SIGNOR-76470 |
P63000 | Q6ZUM4 | 0 | gtpase-activating protein | down-regulates activity | 0.589 | 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-260482 |
P63000 | Q8IVF5 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.589 | 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-260578 |
P38936 | Q99683 | 0 | phosphorylation | up-regulates | 0.589 | P21cip1 is phosphorylated in vitro by both ask1 and jnk1 at s98. /phosphorylation of p21cip1 at s98, which in vivo appears to be regulated by ask1, may therefore mediate negative feedback in the ask1 signaling pathway. | SIGNOR-153440 |
P46934 | Q9BT67 | 0 | relocalization | up-regulates activity | 0.589 | Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2. | SIGNOR-260997 |
Q9UDT6 | O75122 | 0 | binding | up-regulates activity | 0.589 | CLIP-associating protein (CLASP) 1 and CLASP2 are mammalian microtubule (MT) plus-end binding proteins, which associate with CLIP-170 and CLIP-115.|We demonstrate that the middle part of CLASPs binds directly to EB1 and to MTs. | Both EB1- and cortex-binding domains of CLASP are required to promote MT stability. | SIGNOR-265093 |
P63092 | P30518 | 0 | binding | up-regulates activity | 0.589 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256754 |
P23409 | Q02078 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.589 | Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. | SIGNOR-238709 |
P18084 | Q9Y490 | 0 | binding | up-regulates activity | 0.589 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails. | SIGNOR-257629 |
Q7L2Z9 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.588 | Notably, although Plk1 did not alter the level of PBIP1 and CENP-Q ubiquitination, Plk1-dependent phosphorylation and delocalization of these proteins from kinetochores appeared to indirectly lead to their degradation in the cytosol. From these analyses, we identified nine CENP-Q residues (Thr-123, Thr-135, Ser-138, Ser-139, Ser-248, Ser-249, Ser-253, Ser-255, and Thr-256) that were phosphorylated in both in vitro and in vivo samples (Fig. 4B), suggesting that Plk1 phosphorylates these sites. | SIGNOR-265227 |
Q9Y4K3 | Q9C0C7 | 0 | binding | up-regulates activity | 0.588 | In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. | SIGNOR-272963 |
O00206 | P12931 | 0 | phosphorylation | up-regulates activity | 0.588 | Src dependent phosphorylation of TLR4 is significantly increased in Cftr-KO cholangiocytes.|TLR4 can be activated through the phosphorylation of its TIR domains by Src, a non receptor tyrosine kinase 28. | SIGNOR-279658 |
P21860 | P04626 | 0 | binding | up-regulates | 0.588 | Although ErbB-2 binds no known ligand, when recruited into heterodimers it increases ligand binding affinity | SIGNOR-99569 |
Q7KZI7 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.588 | MARK family kinases can be activated by phosphorylation of a conserved threonine (Thr-208 in MARK2), and inactivated by phosphorylation of a serine (Ser-212), both in the activation loop of the catalytic domain. Activation is achieved by the kinases MARKK/TAO1 or LKB1, although the inactivating kinase was unknown. We show here that GSK3beta serves the role of the inhibitory kinase. | SIGNOR-276165 |
P06401 | Q9Y618 | 0 | acetylation | down-regulates | 0.588 | In this study we assessed the effect of smrt and dax-1 on ar and pr activity in the presence of both agonists and partial antagonists. We show that smrt and dax-1 repress agonist-dependent activity of both receptors, and the mechanism of repression includes disruption of the receptor dimer interactions rather than recruitment of histone deacetylases. | SIGNOR-101289 |
P46531 | Q9UQ52 | 0 | relocalization | up-regulates | 0.588 | Here, we establish that nb-3, a member of the f3/contactin family, acts as a novel notch ligand to participate in oligodendrocyte generation. Nb-3 triggers nuclear translocation of the notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via deltex1. | SIGNOR-124151 |
P17302 | P12931 | 0 | phosphorylation | down-regulates | 0.588 | The oncogenic tyrosine kinase, v-src, phosphorylates connexin43 (cx43) on y247 and y265 and inhibits cx43 gap junctional communication (gjc), the process of intercellular exchange of ions and metabolites. | SIGNOR-148913 |
P43403 | P29350 | 0 | dephosphorylation | down-regulates | 0.588 | We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene. | SIGNOR-70237 |
P63000 | O75044 | 0 | gtpase-activating protein | down-regulates activity | 0.588 | 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-260516 |
P62714 | Q9NRL3 | 0 | binding | up-regulates activity | 0.588 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261699 |
Q13873 | Q13253 | 0 | binding | down-regulates activity | 0.588 | Noggin binds the domain that is re-quired for bmp-7 to interact with bmp type i and type ii receptors.Noggin Inhibits bmp by blocking the molecular interfaces of the binding epitopes for both type i and type ii receptors (pmid 12478285) | SIGNOR-195612 |
P49639 | P55347 | 0 | binding | up-regulates activity | 0.588 | Our results are consistent with a primary interaction of the YPWM motif of HOXA1 with the homeodomain of PBX. HOX proteins are dependent upon cofactors of the PBX family for specificity of DNA binding. | SIGNOR-220242 |
O95644 | P49841 | 0 | phosphorylation | down-regulates activity | 0.588 | In T-cells, calcineurin de-phosphorylates NFATc1, leading to its nuclear import, while glycogen synthase kinase 3 beta (GSK3beta) phosphorylates NFATc1 and promotes its nuclear export.|We conclude that GSK3beta negatively regulates NFATc1 in vSMCs, and GSK3beta must be inactivated to allow NFAT activation during wound repair.Male Sprague-Dawley rats were obtained from Charles River (Montreal, PQ, Canada). | SIGNOR-279185 |
O75197 | Q93097 | 0 | binding | up-regulates | 0.588 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors andinitiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131780 |
Q96RR4 | P0DP25 | 0 | binding | up-regulates | 0.588 | The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk. | SIGNOR-266345 |
Q13283 | Q14444 | 0 | binding | up-regulates activity | 0.588 | Caprin-1 and G3BP-1 were directly or indirectly associated in a stable complex. The Caprin-1/G3BP-1 complex occurs in cytoplasmic RNA granules | SIGNOR-260982 |
P16284 | P06239 | 0 | phosphorylation | up-regulates activity | 0.588 | We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances. | SIGNOR-262742 |
Q8N163 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.587 | Here, we report that, in human cell lines, DNA damage triggered the phosphorylation of DBC1 on Thr454 by ATM (ataxia telangiectasia-mutated) and ATR (ataxia telangiectasia and Rad3-related) kinases. Phosphorylated DBC1 bound to and inhibited SIRT1, resulting in the dissociation of the SIRT1-p53 complex and stimulating p53 acetylation and p53-dependent cell death. | SIGNOR-267661 |
P50148 | Q969V1 | 0 | binding | up-regulates activity | 0.587 | 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-257268 |
Q14790 | Q7Z434 | 0 | relocalization | up-regulates | 0.587 | Another protein suggested to play a role in caspase-8 translocation to mitochondria is the mitochondrial membrane protein cardif | SIGNOR-143572 |
P06493 | P0C1S8 | 0 | phosphorylation | down-regulates activity | 0.587 | Recombinant Wee1B effectively phosphorylated cyclin B-associated Cdk1 on tyrosine-15, resulting in an inactivation of the kinase activity of Cdk1. | SIGNOR-279134 |
O60674 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.587 | K63 linked poly-ubiquitination on K970 of JAK2 kinase domain is promoted by Cbl. | SIGNOR-278538 |
P11802 | P50613 | 0 | phosphorylation | up-regulates | 0.587 | Phosphorylation of cdk4 on threonine 172 by a cdk-activating kinase (cak). therefore, formation of the cyclin d-cdk4 complex and phosphorylation of the bound catalytic subunit are independently regulated, and in addition to the requirement for cak activity, serum stimulation is required to promote assembly of the complexes in mammalian cells. | SIGNOR-36549 |
O75197 | Q9H1J7 | 0 | binding | up-regulates | 0.587 | 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-131885 |
Q14980 | P06493 | 0 | phosphorylation | down-regulates | 0.587 | Cdk1-mediated phosphorylation at t2055 negatively regulates numa cortical localization and that this phosphorylation is counteracted by ppp2ca phosphatase activity. | SIGNOR-194825 |
P32121 | Q02750 | 0 | phosphorylation | up-regulates activity | 0.587 | Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a _-arrestin-dependent mechanism, promotes MEK-dependent _-arrestin2 phosphorylation at Thr383 | SIGNOR-252027 |
P08238 | P12931 | 0 | phosphorylation | up-regulates | 0.587 | C-src directly phosphorylates hsp90 on tyrosine 300 residue and that this event is essential for vegf-stimulated enos association to hsp90 and thus no release from endothelial cells. | SIGNOR-157781 |
Q86VW2 | P50148 | 0 | binding | up-regulates activity | 0.587 | P63RhoGEF is autoinhibited by the Dbl homology (DH)-associated pleckstrin homology (PH) domain; activated Galpha(q) relieves this autoinhibition by interacting with a highly conserved C-terminal extension of the PH domain | SIGNOR-256493 |
Q92918 | P46109 | 0 | binding | up-regulates | 0.587 | We found that hpk1 interacted with crk and crkl adaptor proteins in vitro and in vivo and that the proline-rich motifs within hpk1 were involved in the differential interaction of hpk1 with the crk proteins and grb2. Crk and crkl not only activated hpk1 but also synergized with hpk1 in the activation of jnk. | SIGNOR-63991 |
P10275 | Q16512 | 0 | phosphorylation | up-regulates | 0.587 | Rho can sensitize the ar to low levels of circulating androgens by promoting the nuclear translocation of a transcriptional co-activator, fhl2 (four and a half lim domains 2), which binds ar, and by stimulating protein kinase n (pkn), which phosphorylates ar directly. | SIGNOR-152762 |
P19838 | P20749 | 0 | binding | up-regulates activity | 0.587 | In the present study, we report that regulation of CTCF by extracellular stress signals is dependent upon activations of an oxidative stress-regulated protein Bcl-3. We found that activated Bcl-3 was able to bind to the κB sites identified in the CTCF promoter region. Bcl-3 was activated by UV irradiation to interact with NF-κB p50 by forming a Bcl-3/p50 heterodimer complex. The Bcl-3/p50 complex suppressed CTCF promoter activity to down-regulate CTCF transcription. | SIGNOR-254789 |
P10275 | P31749 | 0 | phosphorylation | down-regulates activity | 0.586 | Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Here, we demonstrate that akt phosphorylates the androgen receptor (ar) at ser-210 and ser-790 | SIGNOR-108508 |
O75676 | P27361 | 0 | phosphorylation | up-regulates | 0.586 | Rsk-b is a p38alphamapk substrate, and activated by p38alphamapk and, more weakly, by erk1 | SIGNOR-60998 |
Q12933 | P36941 | 0 | binding | up-regulates activity | 0.586 | Endogenous association of traf2, traf3, ciap1, and smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis. | SIGNOR-97950 |
Q9UBK2 | Q16539 | 0 | phosphorylation | up-regulates | 0.586 | Cytokine stimulation of energy expenditure through p38 map kinase activation of ppargamma coactivator-1we show here that many cytokines activate the transcriptional ppar gamma coactivator-1 (pgc-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of pgc-1 proteinp38 mapk directly phosphorylates pgc-1 on residues threonine 262, serine 265, and threonine 298 | SIGNOR-112774 |
O60237 | Q13464 | 0 | phosphorylation | down-regulates | 0.586 | Phosphorylation of ppp1r12b on threonine 646 by rho kinase inhibits the activity of the pp1c-ppp1r12b complex. | SIGNOR-198812 |
P35222 | Q9ULB4 | 0 | binding | up-regulates activity | 0.586 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265871 |
P84022 | Q9UPN9 | 0 | binding | up-regulates activity | 0.586 | The ubiquitious nuclear protein transcriptional intermediary factor 1gamma (tif1gamma) selectively binds receptor-phosphorylated smad2/3 in competition with smad4. Rapid and robust binding of tif1gamma to smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to tgfbeta. Tif1gamma mediates the differentiation response while smad4 mediates the antiproliferative response with smad2/3 participating in both responses. | SIGNOR-236060 |
P63000 | Q9H0H5 | 0 | gtpase-activating protein | down-regulates activity | 0.586 | 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-260512 |
P49768 | P49841 | 0 | phosphorylation | down-regulates activity | 0.586 | We demonstrate that phosphorylation of serines 353 and 357 by glycogen synthase kinase-3beta (gsk3beta) induces a structural change of the hydrophilic loop of ps1the structural change of ps1 reduces the interaction with beta-catenin leading to decreased phosphorylation and ubiquitination of beta-catenin. | SIGNOR-153627 |
Q16665 | P28482 | 0 | phosphorylation | up-regulates | 0.586 | We show that at least two different nuclear protein kinases, one of them identified as p42/p44 mapk, can modify hif-1_. Analysis of in vitro phosphorylated hif-1_ by mass spectroscopy revealed residues ser-641 and ser-643 as possible mapk phosphorylation sites these data suggest that phosphorylation of ser-641/643 by mapk promotes the nuclear accumulation and transcriptional activity of hif-1_ | SIGNOR-178723 |
P35222 | Q9Y6N8 | 0 | binding | up-regulates activity | 0.586 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265850 |
Q99558 | Q12933 | 0 | binding | down-regulates quantity by destabilization | 0.586 | We report here that one important mechanism of nik regulation is through its dynamic interaction with the tumor necrosis factor receptor-associated factor 3 (traf3). Traf3 physically associates with nik via a specific sequence motif located in the n-terminal region of nik; this molecular interaction appears to target nik for degradation by the proteasome. | SIGNOR-124233 |
P25963 | P06239 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.586 | Loss of tyrosine kinase p56lck in Jurkat cells abolished NFkappaB activation and partially suppressed and delayed phosphorylation of Tyr-42 of IkappaB upon pervanadate treatment. |Transfection of these cells with wild type Lck but not with mutant Lck F394 followed by H/R induces the tyrosine phosphorylation of inhibitor of nuclear factor kappaB (IkappaBalpha) and transcriptional activation of NFkappaB, and these are inhibited by Lck inhibitors | SIGNOR-249374 |
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