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 |
|---|---|---|---|---|---|---|---|
O95235 | Q96GD4 | 0 | phosphorylation | down-regulates activity | 0.781 | We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878. | SIGNOR-262659 |
P04637 | O14757 | 0 | phosphorylation | up-regulates activity | 0.78 | Phosphorylation by chk1 of at least three of these sites, Ser366, Ser378, and Thr387, was induced by DNA damage. | SIGNOR-217861 |
P15336 | P45983 | 0 | phosphorylation | up-regulates | 0.78 | Activating transcription factor-2 (atf2) was found to be a target of the jnk signal transduction pathway. Atf2 was phosphorylated by jnk on two closely spaced threonine residues within the nh2-terminal activation domain. | SIGNOR-33914 |
P29590 | P63165 | 0 | sumoylation | up-regulates | 0.78 | We have shown previously that wild type PML, but not PML-RARalpha, is covalently modified by the sentrin family of ubiquitin-like proteins|We show that Lys65 in the RING finger domain, Lys160 in the B1 Box, and Lys490 in the nuclear localization signal contributes three major sentrinization sites| Furthermore, the triple substitution mutant is localized predominantly to the nucleoplasm, in contrast to wild type PML, which is localized to the nuclear bodies. Thus, sentrinization of PML, in the context of the RING finger and the B1 box, regulates nuclear body formation. | SIGNOR-261786 |
P23458 | Q8IU57 | 0 | binding | up-regulates | 0.78 | Each r1-type chain (il-10r1, il-20r1, il-22r1, ifn-_r1 and ifn-_r1) is associated with jak1 tyrosine kinase and mediates recruitment of a variety of signaling molecules after being phosphorylated on its intracellular domain. | SIGNOR-124480 |
P25024 | P10145 | 0 | binding | up-regulates | 0.78 | Il-8 activates both the cxcr1 and the cxcr2 on microvascular endothelial cells, using different signal transduction cascades. | SIGNOR-107920 |
Q9H0H5 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.78 | It was found that the 5A fragment in which five Ser/Thr residues were substituted with Ala (S144A/T145A/S185A/T186A/S187A) fully prevented phosphorylation (Fig. 5B), confirming that Aurora B primarily phosphorylates five Ser/Thr residues in the basic region of MgcRacGAP. | the strong phosphorylation of the basic region of MgcRacGAP by Aurora B kinase was demonstrated, and this phosphorylation prevents the inhibition of MgcRacGAP GAP activity by PRC1 | SIGNOR-250590 |
P01111 | Q07889 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.78 | Sos and Ras-GRF are two families of guanine nucleotide exchange factors that activate Ras proteins in cells. Sos proteins are ubiquitously expressed and are activated in response to cell-surface tyrosine kinase stimulation Sos1 and Ras-GRF1 activate the Ras proteins Ha-Ras, N-Ras, and Ki-Ras | SIGNOR-110566 |
P12004 | Q14527 | 0 | ubiquitination | up-regulates activity | 0.78 | HLTF promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability. | SIGNOR-278608 |
Q13873 | P12644 | 0 | binding | up-regulates | 0.78 | Bmp-4 bound to alk-3 and alk-6 efficiently | SIGNOR-35763 |
P20042 | Q14232 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.78 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269129 |
Q06124 | Q8WU20 | 0 | phosphorylation | up-regulates | 0.78 | In addition to the direct interactions with grb2, tyrosine-phosphorylated frs2 forms a complex with the sh2 domain-containing protein tyrosine phosphatase shp2. This interaction results in tyrosine phosphorylation of shp2 and complex formation between shp2 and grb2. the catalytic activity of shp2 is essential for a sustained map kinase response and for potentiation of fgf-induced neurite outgrowth in pc12 cells | SIGNOR-58196 |
Q14693 | O95476 | 0 | dephosphorylation | up-regulates activity | 0.78 | Dullard significantly dephosphorylates mouse lipin 1b only in BHK cells (Fig. 5A). This is most clearly seen by using the antibody prepared against the phosphorylation site Ser-106.|Dephosphorylation of lipin results in its translocation to the nuclear envelope and endoplasmic reticulum membranes from the cytosol and generation of diacylglycerol | SIGNOR-248346 |
O00401 | P16333 | 0 | binding | up-regulates | 0.78 | Nck and cdc42 activate n-wasp by redundant mechanisms. | SIGNOR-107634 |
O60216 | Q14674 | 0 | cleavage | down-regulates quantity by destabilization | 0.78 | In order to segregate sister chromatids to opposite poles in anaphase, cohesin has to be removed from chromosomes. In budding yeast, the prevalent mode of cohesin removal is by proteolytic cleavage of the Scc1 subunit at the onset of anaphase by the endopeptidase separase | SIGNOR-275537 |
P58753 | O00206 | 0 | binding | up-regulates activity | 0.78 | Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TlR-domain-containing protein in the human genome. Mal activates NF-_B, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. | SIGNOR-252064 |
Q13608 | Q7Z412 | 0 | binding | up-regulates activity | 0.78 | Pex26 recruits Pex6–Pex1 complexes to peroxisomes. Pex26 anchors Pex6 and Pex1 through Pex26–Pex6 and Pex6–Pex1 interactions. | SIGNOR-253614 |
P06730 | Q9BUB5 | 0 | phosphorylation | up-regulates | 0.779 | Mnk1 and mnk2 regulate protein synthesis by phosphorylating the initiation factor eif4e. | SIGNOR-166646 |
P38936 | P01106 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.779 | C-myc also directly represses transcription of cdk kinase inhibitors including p27kip1, p21cip1, p15ink4b and p16ink4a | SIGNOR-102740 |
P01042 | P03952 | 0 | cleavage | up-regulates activity | 0.779 | Bradykinin is a nonapeptide composed of the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg and functions as an inflammatory mediator. BK is the product of the kallikrein–kinin system following activation of FXII. FXIIa leads to proteolysis of PK, and the resulting PKa cleaves HK to generate BK (Figure 1). | SIGNOR-263548 |
P35568 | P18031 | 0 | dephosphorylation | down-regulates | 0.779 | Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. | SIGNOR-74852 |
P31749 | Q13418 | 0 | phosphorylation | up-regulates | 0.779 | Ilk can phosphorylate pkb-akt on serine-473, whereas kinase-deficient ilk severely inhibits endogenous phosphorylation of pkb-akt on serine-473, demonstrating that ilk is involved in agonist stimulated, pi(3)k-dependent, pkb-akt activation. | SIGNOR-252597 |
Q8WU20 | P04629 | 0 | binding | up-regulates | 0.779 | The signaling adapter frs-2 competes with shc for binding to the nerve growth factor receptor trka:a model for discriminating proliferation and differentiation | SIGNOR-65955 |
Q92529-2 | P04629 | 0 | phosphorylation | up-regulates activity | 0.778 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273915 |
P16885 | Q06187 | 0 | phosphorylation | up-regulates | 0.778 | By measuring the ability of human plcgamma2 to restore calcium responses to the b-cell receptor stimulation or oxidative stress in a b-cell line (dt40) deficient in plcgamma2, we have demonstrated that two tyrosine residues, tyr(753) and tyr(759), were important for the plcgamma2 signaling function.Of the two kinases that previously have been proposed to phosphorylate plcgamma2, btk, and syk, purified btk had much greater ability to phosphorylate recombinant plcgamma2 in vitro, whereas syk efficiently phosphorylated adapter protein blnk. | SIGNOR-111069 |
P48736 | P01116 | 0 | binding | up-regulates | 0.778 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner. | SIGNOR-59819 |
Q15796 | O75593 | 0 | binding | up-regulates activity | 0.778 | FAST-2 also interacts directly with Smad2, a cytoplasmic protein which is translocated to the nucleus in response to TGF-beta, and forms a multimeric complex with Smad2 and Smad4 on the activin response element, a high-affinity binding site for FAST-1. | SIGNOR-108333 |
Q13094 | Q92918 | 0 | phosphorylation | up-regulates | 0.778 | The serine/threonine kinase hpk-1 phosphorylates serine 376 of slp-76 and induces the interaction with 14-3-3 proteins | SIGNOR-153613 |
P04637 | O14965 | 0 | phosphorylation | up-regulates activity | 0.778 | The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A | SIGNOR-120836 |
Q13153 | P15153 | 0 | binding | up-regulates | 0.778 | This report shows that rac1 binds to and stimulates the kinase activity of pak1 approximately 2- and 4-5-fold, respectively, better than rac2. | SIGNOR-59546 |
P04637 | P28482 | 0 | phosphorylation | up-regulates activity | 0.778 | In summary, our results suggest that phosphorylation of p53Thr55 by ERK2 is important for doxorubicin-induced p53 activation and cell death. | SIGNOR-279068 |
P32245 | P01189 | 0 | binding | up-regulates activity | 0.778 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268710 |
P03372 | P12931 | 0 | phosphorylation | up-regulates | 0.778 | Although the molecular mechanisms underlying ligand-independent activation of era are not completely understood, phosphorylation of a serine residue in af1 has been implicated in the response to epidermal growth factor. Era is also a target for tyrosine phosphorylation, anda single tyrosine residue located immediately adjacent to af2 has been identified as a substrate for src-family tyrosine kinases. | SIGNOR-55857 |
P24928 | P50750 | 0 | phosphorylation | up-regulates | 0.777 | Cyclin-dependent kinase 9 (cdk9) promotes elongation by rna polymerase ii (rnapii), mrna processing, and co-transcriptional histone modification. Cdk9 phosphorylates multiple targets, including the conserved rnapii elongation factor spt5 and rnapii itself | SIGNOR-203528 |
P47871 | P01275 | 0 | binding | up-regulates | 0.777 | In contrast, stimulation of gs-coupled receptors by glucagon or epinephrine activates lats1/2 kinase activity, thereby inhibiting yap function. | SIGNOR-198504 |
P60953 | P10911 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.777 | 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-260558 |
Q86UR1 | Q8NFA2 | 0 | relocalization | up-regulates activity | 0.777 | Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation | SIGNOR-264709 |
Q9UD71 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.777 | We find that DARPP-32 is converted into an inhibitor of PKA when phosphorylated at threonine 75 by cyclin-dependent kinase 5 (Cdk5). Cdk5 phosphorylates DARPP-32 in vitro and in intact brain cells. Phospho-Thr 75 DARPP-32 inhibits PKA in vitro by a competitive mechanism. | SIGNOR-250671 |
Q8WU20 | P21802 | 0 | phosphorylation | up-regulates activity | 0.777 | In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway. | SIGNOR-236950 |
Q8IYT8 | P42345 | 0 | phosphorylation | down-regulates | 0.777 | Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2 | SIGNOR-183961 |
P61586 | Q9NR81 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.777 | 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-260530 |
P25025 | P09341 | 0 | binding | up-regulates activity | 0.777 | CXCL1 produces cellular chemotactic activity by binding to the CXC chemokine receptor 2 (CXCR2). In PC, this chemokine has been associated with a variety of carcinogenic mechanisms, including oncogene-induced senescence (OIS), angiogenesis, cancer metastasis, and immunosuppressive microenvironments | SIGNOR-277717 |
O60566 | P06493 | 0 | phosphorylation | up-regulates | 0.777 | Here, we demonstrate that bubr1 is phosphorylated on the cdk1 site t620, which triggers the recruitment of plk1 and phosphorylation of bubr1 by plk1 both in vitro and in vivo. Phosphorylation does not appear to be required for spindle checkpoint function but instead is important for the stability of kinetochore-microtubule (kt-mt) interactions | SIGNOR-157642 |
P31391 | P61278 | 0 | binding | up-regulates | 0.777 | The five receptor subtypes bind the natural SST peptides, SST-14 and SST-28, with low nanomolar affinity. | SIGNOR-82496 |
P21579 | Q8WXE9 | 0 | binding | up-regulates quantity | 0.777 | the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively .Stonin-2 and AP-2 are also Required for Efficient Synaptotagmin-1 Retrieval. the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. | SIGNOR-264115 |
P16471 | P01241 | 0 | binding | up-regulates | 0.777 | Hprl does not bind to the hgh receptor, but hgh binds to both the hghr and hprlr, and mutagenesis studies have shown that the receptor-binding sites on hgh overlap. | SIGNOR-35575 |
P49682 | O14625 | 0 | binding | up-regulates activity | 0.777 | The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells. | SIGNOR-260971 |
O43614 | O43612 | 0 | binding | up-regulates | 0.776 | Identification and initial biological characterization of two orexins as well as their two receptors | SIGNOR-55848 |
O00267 | P50750 | 0 | phosphorylation | up-regulates | 0.776 | We describe an evolutionarily conserved repetitive heptapeptide motif (consensus = g-s-r/q-t-p) in the c-terminal region (ctr) of hspt5, which, like the c-terminal domain (ctd) of rna pol ii, is highly phosphorylated by p-tefb. Thr-4 residues of the ctr repeats are functionally important phosphorylation sites. In vitro, thr-4 phosphorylation is critical for the elongation activation activity of dsif | SIGNOR-143939 |
Q15796 | Q13705 | 0 | phosphorylation | up-regulates activity | 0.776 | It has been suggested that binding of myostatin to the ActRIIB results in the phosphorylation of two serine residues of Smad2 or Smad3 at COOH domains | SIGNOR-254984 |
P35222 | Q5JTC6 | 0 | binding | down-regulates activity | 0.776 | We show that Amer1 binds directly to beta-catenin via a novel interaction motif, the REA repeats. This amino acid motif, including the core sequence arginine, glutamic acid and alanine, and this REA repeats mediate binding of Amer1 to the armadillo repeats of beta-catenin. The data suggest that Amer1 exerts its negative regulatory role in Wnt signaling by acting as a scaffold protein for the beta-catenin destruction complex and promoting stabilization of Axin at the plasma membrane. | SIGNOR-217950 |
P33151 | O60716 | 0 | binding | up-regulates quantity by stabilization | 0.776 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252126 |
P78352 | Q8N2Q7 | 0 | relocalization | up-regulates activity | 0.776 | Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions. | SIGNOR-264191 |
Q93038 | O95150 | 0 | binding | up-regulates | 0.776 | The ligand of dr3 is tl1a | SIGNOR-103078 |
O14746 | P51532 | 0 | binding | up-regulates | 0.776 | Tert activates wnt reporter plasmids in a brg1-dependent manner. | SIGNOR-186607 |
P23588 | P23443 | 0 | phosphorylation | up-regulates | 0.776 | S6k1/s6k2 specifically phosphorylate ser422 in vitro. Substitution of ser422 with ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eif4b function. | SIGNOR-123997 |
P42574 | Q16539 | 0 | phosphorylation | down-regulates | 0.775 | Consequently, p38-mapk can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response. | SIGNOR-122099 |
Q8IXI2 | Q9BXM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.775 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272728 |
P37088 | Q96PU5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.775 | The serum and glucocorticoid inducible kinase 1 (SGK1) is induced in the aldosterone sensitive distal nephron (ASDN) where it may stimulate Na reabsorption, partly by inhibiting ubiquitin ligase Nedd4-2-mediated retrieval of epithelial Na+ channel ENaC from the luminal membrane. | SIGNOR-251948 |
P55211 | P31749 | 0 | phosphorylation | down-regulates activity | 0.775 | Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity | SIGNOR-252581 |
Q9BXL7 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.775 | NF-kappaB activation is triggered by PKCteta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCteta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCteta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-249193 |
Q9P244 | P78352 | 0 | binding | up-regulates activity | 0.775 | SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. Interactions between SALMs 1–3 and PSD-95 family proteinscould serve a number of functions. SALM1 and SALM2, which lack the ability to interact with a presynaptic ligand and thus cannot be directly targeted to sites of early synaptic adhesion, may require PSD-95 binding for their localization to early synapses. | SIGNOR-264095 |
P42224 | P29597 | 0 | phosphorylation | up-regulates activity | 0.775 | Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701Phosphorylation of purified Stat1 was necessary and sufficient for the acquisition of DNA binding activity. | SIGNOR-246943 |
P01112 | P12931 | 0 | phosphorylation | down-regulates activity | 0.775 | Src binds to and phosphorylates GTP-, but not GDP-, loaded Ras on a conserved Y32 residue within the switch I region in vitro and that in vivo, Ras-Y32 phosphorylation markedly reduces the binding to effector Raf and concomitantly increases binding to GTPase-activating proteins and the rate of GTP hydrolysis | SIGNOR-252093 |
P09874 | P42574 | 0 | cleavage | down-regulates activity | 0.775 | Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process | SIGNOR-116178 |
P54132 | Q13315 | 0 | phosphorylation | up-regulates | 0.775 | Mitotic phosphorylation of blm was partially dependent on atm, and phosphorylation sites on blm were identified. A phosphospecific antibody against one of these sites (thr-99) revealed radiation-induced phosphorylation, which was defective in ataxia-telangiectasia cells. These data suggest that atm and blm function together in recognizing abnormal dna structures by direct interaction and that these phosphorylation sites in blm are important for radiosensitivity status but not for sce frequency. | SIGNOR-88010 |
P19174 | P43405 | 0 | phosphorylation | up-regulates activity | 0.775 | Syk isolated from antigen receptor-activated B cells phosphorylated PLC-gamma1 on Tyr-771 and the key regulatory residue Tyr-783 in vitro, whereas Lyn from the same B cells phosphorylated PLC-gamma1 only on Tyr-771. | SIGNOR-246576 |
Q01974 | P41221 | 0 | binding | up-regulates | 0.775 | Wnt5a induces ROR1/ROR2 heterooligomerization to enhance leukemia chemotaxis and proliferation|Evolutionarily conserved receptor tyrosine kinase–like orphan receptor-1 and -2 (ROR1/2) are considered distinct receptors for Wnt5a and are implicated in noncanonical Wnt signaling in organogenesis and cancer metastasis. | SIGNOR-199647 |
Q07817 | P45983 | 0 | phosphorylation | down-regulates | 0.775 | By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-me-induced bcl-xl phosphorylation in prostate cancer cells. Further studies with the inhibitor of jun kinase (jnk) and phosphorylation mutant of bcl-xl reveal the augmentative role of jnk-mediated bcl-xl phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of bcl-xl by stress response kinase signaling might oppose the anti-apoptotic function of bcl-xl to permit prostate cancer cells to die by apoptosis | SIGNOR-99219 |
P46531 | P35222 | 0 | binding | up-regulates | 0.775 | Beta-catenin can regulate the level and transcriptional activity of the notch1 and notch1 intracellular domain (nicd). The in vivo and in vitro results demonstrate that beta-catenin binds with notch1 and nicd, for which its armadillo repeat domain is essential. | SIGNOR-236858 |
Q13114 | Q96G74 | 0 | deubiquitination | down-regulates activity | 0.775 | TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. | SIGNOR-265873 |
P61586 | Q13459 | 0 | gtpase-activating protein | down-regulates activity | 0.774 | 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-260509 |
P32245 | O00253 | 0 | binding | down-regulates | 0.774 | Recombinant agouti-related protein was a potent, selective antagonist of mc3r and mc4r,. | SIGNOR-51104 |
P69905 | Q9NZD4 | 0 | binding | up-regulates quantity by stabilization | 0.774 | α-Hemoglobin stabilizing protein (AHSP) binds α-hemoglobin (Hb), avoiding its precipitation and its pro-oxidant activity. | SIGNOR-251770 |
P68871 | P00738 | 0 | binding | down-regulates quantity | 0.774 | Haptoglobin forms a complex of extremely high affinity with Hb via a well-characterized globin site. Our results show that upon Hb-haptoglobin binding, the globin radical, loses its ability to be terminated by forming globin dimers. | SIGNOR-251815 |
O14974 | Q13464 | 0 | phosphorylation | down-regulates activity | 0.774 | Phosphorylation by Rho-kinase inhibited MP activity and this reflected a decrease in V(max). Activity of MP with different substrates also was inhibited by phosphorylation. Two major sites of phosphorylation on MYPT1 were Thr(695) and Thr(850). | SIGNOR-249034 |
Q9Y5J3 | P46531 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.774 | These data establish that HERP2 is a novel primary target gene of Notch that, together with HES, may effect diverse biological activities of Notch | SIGNOR-235397 |
O15169 | O95271 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.774 | Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. | SIGNOR-187972 |
O00238 | P43026 | 0 | binding | up-regulates activity | 0.774 | In contrast to other members of the TGF-beta superfamily, GDF-5 shows a pronounced specificity in type I receptor interaction in cross-link experiments binding only to BMP receptor IB (BMPR-IB). In mice, deletion of either GDF-5 or BMPR-IB results in a similar phenotype, indicating that GDF-5 signaling is highly dependent on BMPR-IB. | SIGNOR-256483 |
Q9BV73 | P51955 | 0 | phosphorylation | down-regulates | 0.774 | C-nap1 hyperphosphorylation triggers the loss of both oligomerization and, crucially, interaction with the core centriole proximal-end protein, cep135. All three of these sites were identified in our in vivo analysis but only two (s2234 and s2394) were identified as nek2 phosphorylation sites in vitro. | SIGNOR-204837 |
P04637 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.773 | P38 regulates p53, but also in p53-defective tumor cells rewire their checkpoint response and become dependent in the p38/mk2 pathway in mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site. | SIGNOR-155246 |
Q06609 | P00519 | 0 | phosphorylation | up-regulates activity | 0.773 | C-Abl phosphorylates Rad51 in vitro and in vivo. phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. c-Abl phosphorylates Rad51 Tyr315 | SIGNOR-251434 |
P05362 | P11215 | 0 | binding | up-regulates | 0.773 | Before leaving the vessel lumen, neutrophils crawl on the endothelium, primarily using cell surface Mac-1 integrins binding to endothelial ICAM-1. | SIGNOR-255041 |
Q9HAW4 | P53350 | 0 | phosphorylation | down-regulates | 0.773 | We show that claspin, an adaptor protein required for chk1 activation, becomes degraded at the onset of mitosis. Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbtrcp ubiquitin ligase. This interaction was phosphorylation dependent and required the activity of the plk1 kinase | SIGNOR-148442 |
Q9Y2T1 | O95271 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.773 | Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. | SIGNOR-187975 |
P31749 | Q6ZVD8 | 0 | dephosphorylation | down-regulates | 0.773 | Here, we identify a protein phosphatase, ph domain leucine-rich repeat protein phosphatase (phlpp), that specifically dephosphorylates the hydrophobic motif of akt (ser473 in akt1), triggering apoptosis and suppressing tumor growth.[...] These data are consistent with phlpp terminating akt signaling by directly dephosphorylating and inactivating akt. | SIGNOR-252602 |
P16234 | P04085 | 0 | binding | up-regulates | 0.773 | Platelet-derived growth factors (pdgf) constitute a family of four gene products (pdgf-a-d) acting by means of two receptor tyrosine kinases, pdgfr alpha and beta. Three of the ligands (pdgf-a, -b, and -c) bind to pdgfr alpha with high affinity. | SIGNOR-114268 |
Q86V24 | Q15848 | 0 | binding | up-regulates | 0.773 | Expression of adipor1/r2 or suppression of adipor1/r2 expression by small-interfering rna supports our conclusion that they serve as receptors for globular and full-length adiponectin, | SIGNOR-101809 |
Q9NZV8 | Q6PIL6 | 0 | relocalization | up-regulates activity | 0.773 | KChIP4 increased the current amplitude of Kv4.2, decelerated the inactivation, and accelerated the recovery from inactivation of Kv4.2. KChIP.is known to promote the translocation of Kv4.2 from the endoplasmic reticulum or Golgi to the cell surface | SIGNOR-269004 |
P15692 | Q16665 | 0 | transcriptional regulation | up-regulates quantity | 0.773 | Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription. | SIGNOR-256592 |
P35222 | P00533 | 0 | phosphorylation | up-regulates activity | 0.773 | EGFR and TRKA effect on WNT3a mediated Topflash induction was abolished by U0126 or expression of dominant negative LRP6-5A mutant (XREF_FIG), demonstrating that both EGFR and TRKA signal via ERK and LRP6 pathway to upregulate WNT and beta-catenin signaling.|FGFR2, FGFR3, EGFR and TRKA Phosphorylate beta-catenin at Tyr142. | SIGNOR-278309 |
P62993 | P21802 | 0 | phosphorylation | up-regulates | 0.773 | Inhibition of basal fgf receptor signaling by dimeric grb2. | SIGNOR-197980 |
P26842 | P32970 | 0 | binding | up-regulates | 0.772 | The molecule defining the cd70 ag is identical to the recently defined ligand for cd27. Bioassays demonstrated that the cd70 cdna clone expressed in african green monkey kidney cells would induce the proliferation of pha-costimulated t cells. Ramos cells were mixed with increasing numbers of transfected cells that expressed cd70 (cd27l) or cd154 (cd40l), both of which are expressed by activated t cells, in the presence of anti-igm ab. Cd27 ligation as well as cd40 ligation inhibited bcr-mediated apoptosis in a dose-dependent manner. | SIGNOR-36357 |
O95999 | O14920 | 0 | phosphorylation | up-regulates activity | 0.772 | Here we show that the putative downstream kinase IKKbeta is required for initial CBM complex formation. Further, upon engagement of IKKbeta/Malt1/Bcl10 with Carma1, IKKbeta phosphorylates Bcl10 in the C terminus and thereby interferes with Bcl10/Malt1 association and Bcl10-mediated IKKgamma ubiquitination. Since only mutation of all serines 134, 136, 138, 141, and 144 completely prevented signal-induced Bcl10 phosphorylation, the Bcl10 5×S/A mutant was used to elucidate the effects of C-terminal Bcl10 phosphorylation on downstream signaling. | SIGNOR-276292 |
Q9GZM8 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.772 | Three specific phosphorylation sites (Ser198, Thr219 and Ser231) and two weak phosphorylation sites (Ser242 and Thr245) for CDK5/p35 are located in this region of NUDEL | Each single or double mutant compromised,and the triple mutant completely eliminated, interaction with 14-3-3ε. | 14-3-3ε sustains NUDEL phosphorylation and protects it from phosphatase.e dynein motor function. | SIGNOR-250676 |
Q9NRY4 | P12931 | 0 | phosphorylation | up-regulates | 0.772 | Phosphorylation of y1105, but not the minor site, was modulated in vivo to a greater extent by overexpression of c-src than by the egf receptor and was efficiently catalyzed by c-src in vitro. Mutation of y1105 from tyr to phe resulted in complete loss of p-tyr-dependent complex formation, indicating that p-y1105 was the sole p-tyr residue mediating binding to p120 | SIGNOR-61670 |
P32246 | P13501 | 0 | binding | up-regulates | 0.772 | RANTES interacts with specific cell surface receptors, which are coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins (G protein) to activate effectors such as phospholipase C (PLC), ion channels, phospholipase D, and protein kinase C. In addition to the CCR1 receptor, RANTES activates several members of the CC subfamily of chemokine receptors including CCR3, CCR4, and CCR5 | SIGNOR-254367 |
Q9NQB0 | Q9UBE8 | 0 | phosphorylation | down-regulates quantity | 0.772 | NLK Augments the Ubiquitylation Activity of NARF against TCF/LEF. ctivation of NLK induced by unknown ligands leads to the phosphorylation of TCF/LEF. NARF then acts on TCF/LEF as an E3 ubiquitin-ligase and, together with E1 and E2 ubiquitylation enzymes, catalyze the ubiquitylation of TCF/LEF. Finally, ubiquitylated TCF/LEF is degraded by the 26 S proteasome. | SIGNOR-271597 |
Q9HCJ2 | Q9Y2I2 | 0 | binding | up-regulates activity | 0.772 | The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. | SIGNOR-264047 |
P38936 | Q13309 | 0 | ubiquitination | down-regulates | 0.772 | Up-regulation of skp2 by notch signaling enhances proteasome-mediated degradation of the ckis, p27 kip1 and p21 cip1, and causes premature entry into s phase. | SIGNOR-138490 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.