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 |
|---|---|---|---|---|---|---|---|
P21802 | O76093 | 0 | binding | up-regulates | 0.73 | Fgfs bind and activate high-affinity receptor tyrosine kinases. The cloning of fgf receptors (fgfrs) has identified four distinct genes | SIGNOR-42368 |
P51812 | P27361 | 0 | phosphorylation | up-regulates | 0.73 | We have generated two monoclonal antibodies that recognize two phosphorylated sites, p-ser227 and p-thr577, in the n- and c-terminal kinase domains of rsk2, respectively. phosphorylation and activation of rsk2 by uv light involves the erk pathway | SIGNOR-81460 |
O15146 | O75096 | 0 | binding | up-regulates activity | 0.73 | AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer. | SIGNOR-273850 |
P45984 | P45985 | 0 | phosphorylation | up-regulates | 0.729 | Mkk4, which activates p38gamma, p38delta, and jnk2 to phosphorylate p53 on ser-33 and cause a transient g(1) arrest. A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1) | SIGNOR-197998 |
Q9Y6Q6 | Q9Y4K3 | 0 | binding | up-regulates activity | 0.729 | TRAF6 interacts with a novel motif located between residues 340 and 358 of RANK. TRAF6-binding region (340-358), but not the TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF-kappaB activation. | SIGNOR-253045 |
P49815 | P31751 | 0 | phosphorylation | down-regulates | 0.729 | We demonstrate here that tuberin is phosphorylated on s939 and t1462 in response to pi3k activation. Our results are consistent with akt being the pi3k-depen-dent tuberin kinase. The pi3k-akt-mediated phosphorylation of tuberin would inhibit the function of the tuberin-hamartin complex. | SIGNOR-91041 |
P37231 | P17676 | 0 | transcriptional regulation | up-regulates quantity | 0.729 | Induction of C/EBP beta DNA-binding activity in NIH-3T3 beta 2 cells exposed to dexamethasone in the presence of insulin and fetal bovine serum activates the expression of an adipocyte-specific nuclear hormone receptor, PPAR gamma, that stimulates the conversion of these fibroblasts into committed preadipocytes | SIGNOR-255730 |
Q99683 | P31749 | 0 | phosphorylation | down-regulates activity | 0.729 | Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1 akt decreased ask1 kinase activity stimulated by both oxidative stress and overexpression in 293 cells by phosphorylating a consensus akt site at serine 83 of ask1. | SIGNOR-252465 |
O60674 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.729 | Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1 | SIGNOR-248466 |
O14965 | Q6PGQ7 | 0 | binding | up-regulates | 0.729 | Both drosophila and human bora can bind to aurora-a and activate the kinase in vitro. | SIGNOR-148661 |
P45985 | Q13233 | 0 | phosphorylation | up-regulates activity | 0.729 | The gck-ctd-mekk1 interaction is sufficiently stable to support mekk1 s phosphorylation of its substrate, sek1 | SIGNOR-236380 |
P22736 | P31749 | 0 | phosphorylation | down-regulates activity | 0.729 | We show that akt interacts with nur77 and inactivates nur77 by phosphorylation at ser-350 | SIGNOR-252466 |
Q9HB89 | Q5H8A3 | 0 | binding | up-regulates | 0.729 | Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan g protein-coupled receptor fm-4/tgr-1, which was identified to date as the neuromedin u (nmu) receptor, and designate this peptide 'neuromedin s (nms)' because it is specifically expressed in the suprachiasmatic nuclei (scn) of the hypothalamus. | SIGNOR-133074 |
P53675 | Q13492 | 0 | binding | up-regulates | 0.729 | Calm interacts with the clathrin heavy chain through its c-terminal third and with phophoinositides through its ap180 n-terminal homology (anth) domain, promoting assembly of clathrin triskelia into clathrin cagesin vitro | SIGNOR-144733 |
Q9BQQ3 | P53350 | 0 | phosphorylation | down-regulates quantity | 0.729 | As GRASP65 is a substrate of cdc2 and polo-like kinase, manipulation of GRASP65 level may affect the localization and activity of these kinases in cell cycle progression, as suggested by a previous study ( ).|During mitosis, GRASP65 is phosphorylated by two mitotic kinases, cdc2 and polo-like kinase (plk), which leads to GRASP65 deoligomerization and thus Golgi unstacking ( xref , xref ). | SIGNOR-279554 |
Q15465 | Q96F81 | 0 | binding | up-regulates activity | 0.729 | We show that the vertebrate homologue, dispatched-a (dispa) interacts with human sonic hedgehog (hshh) via its cholesterol anchor, and that this interaction is necessary for hshh secretion. binding to dispa is necessary but not sufficient for hshh secretion | SIGNOR-191888 |
Q13094 | P42681 | 0 | phosphorylation | up-regulates | 0.728 | Resting lymphocyte kinase (rlk/txk) targets lymphoid adaptor slp-76 in the cooperative activation of interleukin-2 transcription in t-cells. In this study, we report that rlk phosphorylates slp-76 at its n-terminal yesp/yepp sites. A third tyrosine within the amino-terminal region (y145) appears to be the most important for optimal slp-76 function | SIGNOR-44669 |
P51812 | P28482 | 0 | phosphorylation | up-regulates | 0.728 | Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-161518 |
Q16539 | P46734 | 0 | phosphorylation | up-regulates activity | 0.728 | Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. | SIGNOR-232156 |
P11142 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.728 | BAG-1 stimulates CHIP-induced degradation of the glucocorticoid hormone receptor (GR). A model for the cooperation of CHIP and BAG-1 in coupling Hsc/Hsp70 to the ubiquitin/proteasome system. CHIP associates with Hsc/Hsp70 via its TPR chaperone adaptor (TPR) and, at the same time, recruits E2 ubiquitin-conjugating enzymes of the Ubc4/5 family to the chaperone complex. BAG-1 binds to Hsp70 via its BAG domain (BAG) and utilizes its ubiquitin-like domain (ubl) for proteasomal association | SIGNOR-272588 |
P05198 | P19525 | 0 | phosphorylation | down-regulates activity | 0.728 | Besides PERK, eIF2α can also be phosphorylated by three other kinases: heme-regulated inhibitor kinase (HRI), general control nonderepressible 2 (GCN2), and PKR. PKR is an interferon-stimulated gene (ISG) activated by binding of double-stranded RNA (dsRNA), a common intermediate during the replication of DNA and RNA viruses. Together, these four eIF2α kinases and their convergent downstream signaling pathways are known as the integrated stress response (ISR) | SIGNOR-260168 |
O75197 | Q9H461 | 0 | binding | up-regulates activity | 0.728 | Ligands such as Wnt1, Wnt3a, and Wnt8 couple the seven-transmembrane domain receptor Frizzled (Fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (LRP5/6) to activate WntBeta-catenin signaling. | SIGNOR-169635 |
Q9Y463 | P61962 | 0 | binding | up-regulates activity | 0.728 | Two isoforms of DYRK, DYRK1A and DYRK1B, co-immunoprecipitate with HAN11 when coexpressed in COS cells indicating that the proteins interact in mammalian cells. HAN11 might target DYRKs to cytosolic locations for regulation of specific cellular functions. | SIGNOR-260631 |
P84022 | P12755 | 0 | binding | down-regulates activity | 0.728 | Smad2/3 interacts with c-ski through its c-terminal mh2 domain in a tgf-beta-dependent mannerc-ski is incorporated in the smad dna binding complex, interferes with the interaction of smad3 with a transcriptional co-activator, p300, and in turn recruits hdac. c-ski is thus a transcriptional co-repressor that links smads to hdac in tgf-beta signaling. | SIGNOR-232123 |
P17181 | P05000 | 0 | binding | up-regulates | 0.728 | Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2. | SIGNOR-105979 |
P50591 | Q9UBN6 | 0 | binding | down-regulates | 0.728 | One function of trail-r4 may be inhibition of trail cytotoxicy. Dcr2 functions as an inhibitory apo2l receptor. | SIGNOR-53447 |
P04637 | P49841 | 0 | phosphorylation | up-regulates activity | 0.728 | Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity. | SIGNOR-251258 |
P15531 | Q01105 | 0 | binding | down-regulates | 0.728 | Tumor suppressor nm23-h1 is a granzyme a-activated dnase during ctl-mediated apoptosis, and the nucleosome assembly protein set is its inhibitor. / nm23-h1 binds to set and is released from inhibition by gzma cleavage of set. | SIGNOR-99205 |
P36896 | P13385 | 0 | binding | up-regulates activity | 0.728 | Nodal effects are dependent upon interactions with Cripto, a small cysteine-rich extracellular protein that is attached to the plasma membrane through a glycosyl phosphatidyl inositol linkage. Cripto interacts with Nodal and ALK4, independently, and promotes the formation of a stable high affinity complex with activin type II receptors. | SIGNOR-251938 |
P27986 | P10721 | 0 | binding | up-regulates activity | 0.727 | Tyrosine residue 719 of the c-kit receptor is essential for binding of the P85 subunit of phosphatidylinositol (PI) 3-kinase and for c-kit-associated PI 3-kinase activity in COS-1 cells | SIGNOR-255948 |
P11717 | P01344 | 0 | binding | up-regulates | 0.727 | Insulin-like growth factor ii receptor (igf2r) is a multifunctional cell surface receptor implicated in tumour suppression. Its growth inhibitory activity has been associated with an ability to bind igf-ii. | SIGNOR-115250 |
P49407 | P28482 | 0 | phosphorylation | down-regulates | 0.727 | Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation | SIGNOR-67630 |
Q14457 | P53355 | 0 | phosphorylation | up-regulates | 0.727 | The activated form of DAPK triggers autophagy in a beclin-1-dependent manner. DAPK phosphorylates beclin 1 on Thr 119 located at a crucial position within its BH3 domain, and thus promotes the dissociation of beclin 1 from Bcl-XL and the induction of autophagy. | SIGNOR-183548 |
Q02241 | Q96GD4 | 0 | phosphorylation | down-regulates quantity | 0.727 | Furthermore, reduced turnover of regulatory phosphorylation on another Aurora B substrate MKlp1 was observed, suggesting that PP2A-B56\u03b3 and -\u03b5 play a general role opposing Aurora B at the central spindle.|In anaphase, the KIF4A-targeted pool of B56\u03b3 and -\u03b5 is ideally placed to counteract Aurora B phosphorylations on other central spindle proteins such as MKlp1. | SIGNOR-280192 |
Q9Y6D9 | O43683 | 0 | relocalization | up-regulates activity | 0.727 | Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity | SIGNOR-252017 |
P48551 | Q00978 | 0 | binding | up-regulates activity | 0.727 | By binding to IFNalphaR2 within the region where two adjacent proline boxes bear phospho-Ser364 and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)RF9 interacts with the acetyl-Lys399 motif by means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2. | SIGNOR-217779 |
P51685 | P22362 | 0 | binding | up-regulates | 0.726 | Ccl1 activates the mapk pathway in ccr8-transfected cho cells. | SIGNOR-99401 |
P58753 | O60603 | 0 | binding | up-regulates activity | 0.726 | To initiate the innate immune response, Toll-like receptors (TLRs) associate with cytoplasmic adaptor proteins through TIR (Toll/interleukin-1 receptor) domain interactions. The four principal signaling adaptor proteins include MyD88, MAL, TRIF and TRAM, and the fifth protein SARM, involved in negative regulation of TLR pathways, is usually considered a part of the TIR domain-containing adaptor protein group | SIGNOR-266745 |
P42574 | Q14790 | 0 | cleavage | up-regulates activity | 0.726 | Triggering of the DISC leads to caspase-8 activation. Active caspase-8 cleaves caspase-3 which, in type I cells, leads to cell death induction. | SIGNOR-171767 |
O14793 | P19883 | 0 | binding | down-regulates activity | 0.726 | Follistatin (FST) is a member of the tissue growth factor beta family and is a secreted glycoprotein that antagonizes many members of the family, including activin A, growth differentiation factor 11, and myostatin. FST315-deltaHBS-Fc induced improvements in muscle repair after injury/atrophy by modulating the early inflammatory phase allowing for increased macrophage density, and Pax7-positive cells leading to an accelerated restoration of myofibers and muscle function. | SIGNOR-251717 |
P16220 | P51812 | 0 | phosphorylation | up-regulates activity | 0.726 | MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression | SIGNOR-248951 |
P42702 | P13725 | 0 | binding | up-regulates | 0.726 | Oncostatin m binds the high-affinity leukemia inhibitory factor receptor | SIGNOR-19873 |
P02647 | P00738 | 0 | binding | up-regulates quantity by stabilization | 0.726 | Haptoglobin binding to apolipoprotein A-I prevents damage from hydroxyl radicals on its stimulatory activity of the enzyme lecithin-cholesterol acyl-transferase. haptoglobin, when circulating at enhanced levels with free Hb during the acute phase of inflammation, might protect ApoA-I structure and function against hydroxyl radicals. | SIGNOR-252106 |
Q9NZJ5 | P11021 | 0 | binding | down-regulates activity | 0.726 | In the stressed ER, protein chaperone GRP78 binds to unfolded proteins and dissociates from the luminal domain of PERK, leading to oligomerization and activation of PERK by autophosphorylation. | SIGNOR-260164 |
Q03164 | O00255 | 0 | binding | up-regulates activity | 0.726 | However, menin dramatically increases the amount of MLL bound at the p27Kip1 and p18Ink4c loci, suggesting that it either directly or indirectly promotes MLL recruitment to these targets. Once recruited, MLL could enhance transcription by a number of mechanisms.Overall, the data suggest that transcriptional regulation by menin involves increasing MLL protein association with target loci. | SIGNOR-255890 |
Q9NWQ8 | P07948 | 0 | phosphorylation | up-regulates activity | 0.725 | Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr314, which recruited Csk/Ctk to suppress Lyn kinase activity.Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn. | SIGNOR-262898 |
Q9H461 | P04628 | 0 | binding | up-regulates | 0.725 | Wnt signaling is mediated by the frizzled (fz) family of seven-pass transmembrane receptors that bind wnt via the conserved amino-terminal cysteine-rich domain (crd) | SIGNOR-109250 |
Q14289 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.725 | We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. |We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity. | SIGNOR-277084 |
P63000 | P31749 | 0 | phosphorylation | down-regulates activity | 0.725 | Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1 | SIGNOR-252576 |
Q15797 | Q9HAU4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.725 | Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3. | SIGNOR-272936 |
P42224 | P10721 | 0 | phosphorylation | up-regulates activity | 0.725 | KIT is responsible for the permanent phosphorylation of all three STAT proteins. STAT1, -3, and -5 were phosphorylated on their activation-specific Tyr701, Tyr704, and Tyr694, respectively, following KIT stimulation. | SIGNOR-251365 |
P11717 | O60664 | 0 | relocalization | up-regulates activity | 0.725 | TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi. | SIGNOR-253092 |
P30622 | Q7Z460 | 0 | binding | up-regulates activity | 0.725 | 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-265091 |
P63000 | Q9NRY4 | 0 | gtpase-activating protein | down-regulates activity | 0.724 | 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-260493 |
Q9UGK3 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.724 | Our previous studies revealed that STAP-2 binds to signal transducer and activator of transcription 3 (STAT3) and STAT5, and regulates the signaling pathways downstream of them. In the present study, we identified tyrosine-250 (Tyr250) in STAP-2 as a major site of phosphorylation by Brk, using a series of STAP-2 YF mutants and anti-phospho-STAP-2 Tyr250 antibody. Furthermore, overexpression of the STAP-2 Y250F mutant protein affected Brk-mediated STAT3 activation. | SIGNOR-247067 |
Q16555 | P49841 | 0 | phosphorylation | down-regulates activity | 0.724 | Here, we showed that glycogen synthase kinase-3beta (gsk-3beta) phosphorylated crmp-2 at thr-514 and inactivated it | SIGNOR-133255 |
P07550 | P32121 | 0 | binding | down-regulates activity | 0.724 | The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors | SIGNOR-256501 |
O95644 | P16298 | 0 | relocalization | up-regulates | 0.724 | The ca2+ dependent phosphatase calcineurin induces cardiac and skeletal muscle hypertrophy by a process that involves nf-at nuclear translocation, and activation of mef2c. | SIGNOR-84047 |
P05067 | P55212 | 0 | cleavage | up-regulates activity | 0.724 | Inhibition of caspase-6 activity prevents serum deprivation-mediated increase of Ab. Caspase-6 directly cleaves APP at the C terminus and generates a C-terminal fragment of 3 kDa (Capp3) and an Ab-containing 6.5-kDa fragment, Capp6.5, that increases in serum-deprived neurons | SIGNOR-261762 |
P33991 | Q13535 | 0 | phosphorylation | up-regulates | 0.724 | Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6. | SIGNOR-169412 |
P15498 | P15391 | 0 | binding | up-regulates activity | 0.724 | CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades. | SIGNOR-242897 |
P12757 | Q6ZNA4 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.723 | Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4. | SIGNOR-272885 |
O14733 | Q13233 | 0 | phosphorylation | up-regulates | 0.723 | Here we show that jnkk2, a novel member of the map kinase kinase family, was phosphorylated and activated by mekk1 | SIGNOR-51207 |
P25025 | P19876 | 0 | binding | up-regulates activity | 0.723 | CXCL2/3, also known as macrophage inflammatory protein-2α/2β (MIP-2α/MIP-2β), share the same receptor CXCR2 with CXCL1 and are able to activate neutrophils effectively | SIGNOR-277719 |
P01130 | Q8WY64 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.723 | The RING E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL, also known as MYLIP) promotes ubiquitylation and subsequent lysosomal degradation of the LDL receptor (LDLR), thus acting to limit uptake of lipoprotein-derived cholesterol into cells. | SIGNOR-271485 |
P42338 | P35568 | 0 | binding | up-regulates activity | 0.723 | To examine contributions of specific YXXM motifs in human insulin receptor substrate-1 (IRS-1) to mediating the metabolic actions of insulin, we studied IRS-1 mutants containing various substitutions of Phe for Tyr. In transfected NIH-3T3(IR) cells, insulin stimulation caused a 5-fold increase in phosphatidylinositol 3-kinase (PI3K) activity coimmunoprecipitated with wild-type IRS-1 | SIGNOR-235487 |
P48736 | P27986 | 0 | binding | up-regulates activity | 0.723 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242646 |
O43663 | P53350 | 0 | phosphorylation | down-regulates activity | 0.723 | Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis.|Plk1, but not Cdk1, phosphorylates PRC1 on Thr-602 to prevent premature midzone assembly in metaphase. | SIGNOR-279645 |
O15151 | O96017 | 0 | phosphorylation | down-regulates | 0.723 | Phosphorylation of s342 and s367 in vivo require the chk2 kinase. Chk2 also stimulates mdmx ubiquitination and degradation by mdm2 | SIGNOR-140417 |
Q15303 | P35070 | 0 | binding | up-regulates | 0.723 | For example, betacellulin binds to and activates both erbb1 and erbb4, whereas epiregulin binds to erbb1, erbb3 and erbb4 | SIGNOR-195347 |
P35568 | Q05513 | 0 | phosphorylation | down-regulates activity | 0.723 | Extensive studies have provided evidence that phosphorylation of Ser307 in IRS-1 inhibits IR/IRS-1 complex formation and IRS-1 tyrosine phosphorylation after prolonged insulin-stimulation similar to our results. | SIGNOR-236760 |
O95271 | Q9NTX7 | 0 | ubiquitination | down-regulates quantity | 0.723 | We show that RNF146, tankyrase, and Axin form a protein complex, and that RNF146 mediates ubiquitylation of all three proteins to target them for proteasomal degradation. | SIGNOR-260004 |
P36897 | P37173 | 0 | phosphorylation | up-regulates activity | 0.722 | Recent studies have revealed that upon TGF-beta binding several serine and threonine residues in the GS domain of TGF-beta type I receptor (T beta R-I) are phosphorylated by TGF-beta type II receptor (T beta R-II) and that the phosphorylation of GS domain is essential for TGF-beta signalingThese observations indicate that serine 172 and threonine 176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta | SIGNOR-246728 |
P46108 | P08069 | 0 | phosphorylation | down-regulates activity | 0.722 | On activation of the IGF-I receptor, Crk-II binds to phosphorylated tyrosine residues, especially in the juxtamembrane region. As a result of this binding, the IGF-I receptor kinase phosphorylates Tyr-221 of Crk-II, resulting in a change in intramolecular folding and binding of the SH2 domain to the phosphorylated Tyr-221, which causes rapid disassociation of the Crk-II-IGF-I receptor complex. | SIGNOR-251273 |
Q15796 | P28482 | 0 | phosphorylation | up-regulates | 0.722 | We show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity. | SIGNOR-91714 |
P48736 | P01111 | 0 | binding | up-regulates | 0.722 | 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.llysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175228 |
O14733 | Q9UQF2 | 0 | binding | up-regulates | 0.722 | Both jip1 and jip2 selectively bind the mapkk isoform mkk7. | SIGNOR-70848 |
P60880 | P46459 | 0 | binding | down-regulates activity | 0.722 | NSF is an important regulator of SNARE assembly/disassembly. NSF binds to SNAP-25, while in complex with other SNAREs, and hydrolyzes adenosine triphosphate to disassemble the SNARE complex down to monomers | SIGNOR-263974 |
Q92847 | Q9UBU3 | 0 | binding | up-regulates | 0.722 | In contrast to wild-type mice, acute treatment of ghsr- mice with ghrelin stimulated neither gh release nor food intake, showing that the ghsr is a biologically relevant ghrelin receptor. | SIGNOR-123948 |
P30305 | O14965 | 0 | phosphorylation | up-regulates | 0.722 | We show that bypass of the g2/m checkpoint by the chk1 kinase inhibitor ucn-01 results in the activation of aurora-a and phosphorylation of cdc25b on s353 | SIGNOR-139396 |
P16473 | P01222 | 0 | binding | up-regulates | 0.722 | Two novel human glycoprotein hormonelike genes, alpha2 (a2) and beta5 (b5), recently have been identified. Using a yeast two-hybrid assay, the two subunits were found as potential heterodimerization partners. | SIGNOR-88653 |
P42336 | P35568 | 0 | binding | up-regulates activity | 0.722 | Irs proteins are capable of both regulating and activating pi3k, depending on the cell of origin. | SIGNOR-168985 |
Q04206 | Q96EB6 | 0 | deacetylation | down-regulates activity | 0.722 | SIRT1 physically interacts with the RelA/p65 subunit of NF-kappaB and inhibits transcription by deacetylating RelA/p65 at lysine 310. | SIGNOR-238817 |
P10276 | P28702 | 0 | binding | up-regulates | 0.722 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16674 |
Q03135 | P06241 | 0 | phosphorylation | down-regulates activity | 0.721 | Caveolin-1 is phosphorylated on tyr(14) in response to both oxidative and hyperosmotic stress. In the present paper, we show that this phosphorylation requires activation of the src family kinase fyn.Therefore, | SIGNOR-118003 |
Q08050 | O96017 | 0 | phosphorylation | up-regulates | 0.721 | Chk2 mediates stabilization of the foxm1 transcription factor to stimulate expression of dna repair genesthis phosphorylation of foxm1 on serine residue 361 caused increased stability of the foxm1 protein | SIGNOR-150746 |
Q12955 | Q92823 | 0 | relocalization | up-regulates quantity | 0.721 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266720 |
P46937 | P07947 | 0 | phosphorylation | up-regulates activity | 0.721 | Yes directly phosphorylates YAP and TAZ, resulting in their increased nuclear localization and transcriptional activity.Analysis by mass spectrometry identified Tyr391 and Tyr407 as the two phosphorylation sites of YAP, whereas Tyr305 was the sole phosphorylated residue of TAZ (Fig. 5F and fig. S4, A to C). | SIGNOR-277653 |
O75369 | Q8WUP2 | 0 | binding | up-regulates activity | 0.721 | Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton. | SIGNOR-266106 |
Q99640 | P53350 | 0 | phosphorylation | down-regulates activity | 0.721 | Here, we have shown that Plk1 is responsible for part of the phosphorylation of Myt1 during M phase. The kinase activity of human Myt1 is reported to be decreased during M phase, and the decreased activity correlates with hyperphosphorylated forms of Myt1 (35, 37). We then tested the ability of these mutant forms of Myt1 (GST fusion proteins), to serve as a substrate for Plk1 in vitro. Quantification of the result (Fig. 5C) showed that Ser-426 is the major phosphorylation site by Plk1 in vitro and Thr-495 the second major site. | SIGNOR-263096 |
P01116 | P21359 | 0 | binding | down-regulates activity | 0.721 | Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. | SIGNOR-273661 |
O00571 | Q9UHD2 | 0 | phosphorylation | up-regulates activity | 0.721 | Coexpression of TBK1 strongly increased the activity of DDX3X.|This suggests that DDX3X is rather specifically phosphorylated by TBK1 and IKK-i. | SIGNOR-278997 |
P13569 | Q9HD26 | 0 | binding | down-regulates | 0.721 | Cal binds to cftr / cal affects insertion of cftr to the plasma membrane as well as its half-life in the plasma membrane. | SIGNOR-111671 |
Q13485 | Q15796 | 0 | binding | up-regulates activity | 0.721 | the receptor-regulated Smad, such as Smad2, forms a heterocomplex with the co-mediator Smad, Smad4 | SIGNOR-235183 |
P10828 | P19793 | 0 | binding | up-regulates | 0.721 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81449 |
P40763 | P27361 | 0 | phosphorylation | up-regulates | 0.72 | The activation of stat-3 is regulated by phosphorylation of tyrosine 705 by receptor and nonreceptor protein tyrosine kinases these include epidermal growth factor receptor (egfr) kinase,92 src,5 janus-activated kinases (jak), and extracellular signal-regulated kinase (erk)a constitutively active galpha16 mutant, galpha16ql, stimulated stat3-dependent luciferase activity as well as the phosphorylation of stat3 at both tyr705 and ser727. Galpha16ql-induced stat3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (erk1 | SIGNOR-118596 |
P23443 | P67775 | 0 | dephosphorylation | down-regulates | 0.72 | Protein phosphatase 2a inactivates the mitogen-stimulated s6 kinase from swiss mouse 3t3 cells | SIGNOR-23575 |
P46531 | O00587 | 0 | binding | up-regulates | 0.72 | Manic fringe elongates the o-linked fucose saccharides on full-length notch1 and notch1 egf repeats 1923. | SIGNOR-80555 |
Q92859 | O00634 | 0 | binding | up-regulates activity | 0.72 | Experiments have demonstrated that Neogenin also mediates Netrin-1 attractive functions. Both DCC and Neogenin are type I transmembrane receptors that belong to the immunoglobulin superfamily proteins. | SIGNOR-268171 |
Q08J23 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.72 | Aurora-b phosphorylated nsun2 at ser139. Aurora-b-phosphorylation and the phosphorylation-mimic mutation (s139e) suppressed methyltransferase activities of nsun2. | SIGNOR-152001 |
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