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 |
|---|---|---|---|---|---|---|---|
Q15118 | Q16513 | 1 | phosphorylation | up-regulates activity | 0.338 | PDK1 phosphorylates the PRKs at their conserved activation loop threonines (Thr-774 and Thr-816 for PRK1 and PRK2, respectively) both in vitro and in vivo. | SIGNOR-250265 |
P17612 | O43566 | 1 | phosphorylation | up-regulates activity | 0.338 | RGS14 is phosphorylated in vitro at Ser258 and Thr494 by PKA. cAMP-induced phosphorylation as an important modulator of RGS14 function since phosphorylation could enhance RGS14 binding to Galpha(i)-GDP | SIGNOR-250045 |
O14757 | P12931 | 1 | phosphorylation | up-regulates activity | 0.338 | In this study, we show that Chk1 phosphorylates human Src at the newly identified site serine 51 to fully induce Src kinase activity. | SIGNOR-278332 |
P78527 | P67809 | 1 | phosphorylation | up-regulates activity | 0.338 | The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus. | SIGNOR-277611 |
P19784 | P55087 | 1 | phosphorylation | down-regulates activity | 0.338 | We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. | To determine whether Ser276 is an actual CKII substrate, we used GST–AQP4‐Cter proteins in which only one out of the three C‐terminal CKII consensus sites was sequentially conserved (Ser276, Ser285 and Ser315, respectively). Figure 7B (right panel) shows that the three serine residues, including Ser276, were indeed efficiently phosphorylated by CKII. | SIGNOR-250976 |
P49841 | Q9HB09 | 1 | phosphorylation | up-regulates | 0.338 | Gsk3b phosphorylates bcl2l12 at s156. Ectopic expression of gfp-fused bcl2l12 or bcl2l12a in u87mg cells leads to repression of apoptotic markers and protects against staurosporine (sts) insults, indicating an antiapoptotic role for both bcl2l12 and bcl2l12a. In contrast, no anti-apoptotic ability was seen in bcl2l12(s156a) | SIGNOR-195512 |
P68400 | Q712K3 | 1 | phosphorylation | up-regulates activity | 0.338 | Ck2-dependent phosphorylation of the e2 ubiquitin conjugating enzyme ubc3b induces its interaction with beta-trcp and enhances beta-catenin degradation | SIGNOR-88050 |
P62330 | P48426 | 1 | null | up-regulates activity | 0.338 | Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization. | SIGNOR-264911 |
P06493 | P05783 | 1 | phosphorylation | up-regulates | 0.338 | We identified k18 ser33 as an interphase phosphorylation site, which increases its phosphorylation during mitosis in cultured cells and regenerating liver, and as an in vitro cdc2 kinase phosphorylation site. K18 ser33 phosphorylation dictates binding to 14_3_3 proteins | SIGNOR-55994 |
P68400 | P30305 | 1 | phosphorylation | up-regulates activity | 0.338 | Mass spectrometry analysis demonstrates that at least two serine residues, Ser-186 and Ser-187, are phosphorylated in vivo. | Finally, we demonstrate that phosphorylation of CDC25B by protein kinase CK2 increases the catalytic activity of the phosphatase in vitro as well as in vivo. | SIGNOR-250836 |
P54821 | O15525 | 1 | binding | down-regulates activity | 0.338 | Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf. | SIGNOR-221961 |
Q9H4B4 | Q14790 | 1 | phosphorylation | up-regulates activity | 0.338 | Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. | SIGNOR-272995 |
Q9Y314 | P67775 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.338 | NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice. | SIGNOR-271498 |
Q8NEZ5 | P04637 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.338 | We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. |SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation. | SIGNOR-273448 |
P68400 | O15266 | 1 | phosphorylation | up-regulates | 0.338 | We show also that casein kinase ii phosphorylates shox on serine 106 efficiently in vitro. S106a shox mutant, defective in phosphorylation, does not activate transcription and fails to induce cell-cycle arrest and apoptosis | SIGNOR-142875 |
P17612 | P17600 | 1 | phosphorylation | down-regulates activity | 0.338 | Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I | SIGNOR-250058 |
Q16566 | Q99623 | 1 | phosphorylation | down-regulates | 0.338 | Here we show that calcium/calmodulin-dependent kinase iv (camk iv) specifically binds to the c terminus of phb2 and phosphorylates phb2 at serine 91. Camk iv effectively decreased phb2-mediated repression of mef2 activity through phosphorylation | SIGNOR-174437 |
P31749 | Q9BWT1 | 1 | phosphorylation | down-regulates | 0.338 | The prosurvival kinase akt phosphorylates cdca7 at threonine 163, promoting binding to 14-3-3, dissociation from myc, and sequestration to the cytoplasm. we have mapped the domains of interaction and have discovered that akt phosphorylates cdca7 near this contact region, leading to loss of its association with myc, binding to 14-3-3 proteins, and exclusion from the nucleus. | SIGNOR-252533 |
O43318 | P46937 | 1 | phosphorylation | down-regulates activity | 0.338 | TAK1 inhibits YAP activity through beta-TRCP.|Thus, our data indicate that TAK1 directly phosphorylates YAP at multiple sites.|These observations prompted us to test whether TAK1 phosphorylates YAP at S127. | SIGNOR-278956 |
P23470 | P09619 | 1 | dephosphorylation | down-regulates activity | 0.338 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254715 |
P63000 | P35125 | 1 | relocalization | up-regulates | 0.338 | In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin. | SIGNOR-98938 |
Q5JVS0 | Q06413 | 1 | binding | down-regulates activity | 0.338 | MEF2C DNA-binding activity is inhibited through its interaction with the regulatory protein Ki-1/57. | SIGNOR-238283 |
P17612 | P41240 | 1 | phosphorylation | up-regulates activity | 0.338 | Activation of the cooh-terminal src kinase (csk) by camp-dependent protein kinase inhibits signaling through the t cell receptor.Pka phosphorylates csk at s364 in vitro and in vivo leading to a two- to fourfold increase in csk activity that is necessary for camp-mediated inhibition of tcr-induced interleukin 2 secretion. | SIGNOR-105229 |
Q9UQM7 | P51790 | 1 | phosphorylation | up-regulates activity | 0.337 | Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current|The N-terminus of CLC-3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII-dependent Cl(-) conductance, indicating that this residue is important in the gating of CLC-3 at the plasma membrane. | SIGNOR-275863 |
O00141 | Q92542 | 1 | phosphorylation | down-regulates quantity | 0.337 | Furthermore, SGK1 directly bound to and phosphorylated Nicastrin on Ser437, thereby promoting protein degradation.|We showed that SGK1 downregulates Nicastrin protein levels. | SIGNOR-280122 |
P12931 | Q9UK17 | 1 | phosphorylation | up-regulates activity | 0.337 | These results indicate that Y108 (for Src-family kinases) and Y136 (for EGFR kinase) are involved in the tyrosine phosphorylation of hKv4.3 channels. | SIGNOR-276393 |
Q8NC42 | P15056 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.337 | We showed that RNF149 bound directly to the C-terminal kinase-containing domain of wild-type BRAF and induced ubiquitination, followed by proteasome-dependent degradation, of the latter protein. Functionally, RNF149 attenuated the increase in cell growth induced by wild-type BRAF. | SIGNOR-272043 |
P35813 | Q13153 | 1 | dephosphorylation | down-regulates activity | 0.337 | Purified PP2Cα protein efficiently dephosphorylated PAK1 in vitro (Fig. 1, D and E). We previously assessed the time course of phospho-PAK1 dephosphorylation assessed using specific antibodies against either Ser(P)198/203 or Thr(P)422 sites in the PAK1 activation loop. | SIGNOR-248492 |
O76064 | P54132 | 1 | ubiquitination | up-regulates activity | 0.337 | Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of . | SIGNOR-272115 |
Q14541 | Q92819 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.337 | Transcription was activated by HNF4G in reporter assays using the promoter/enhancer region of the HAS2 gene. The endogenous expression of the HAS2 gene was suppressed by knockdown of HNF4G. | SIGNOR-261626 |
P68400 | P05455 | 1 | phosphorylation | up-regulates | 0.337 | Prior studies indicate that hla is activated by phosphorylation of serine-366 by protein kinase ck2, neutralizing a negative effect of a short basic motif (sbm) | SIGNOR-160761 |
Q05513 | P49768 | 1 | phosphorylation | up-regulates activity | 0.337 | A phosphorylation site at serine residue 346 was identified that is selectively phosphorylated by PKC but not by PKA. This site is localized within a recognition motif for caspases, and phosphorylation strongly inhibits proteolytic processing of PS1 by caspase activity during apoptosis. | SIGNOR-249239 |
P01375 | O75509 | 1 | binding | up-regulates | 0.337 | We report the identification and initial characterization of dr6, a new member of the tnf receptor family possessing a cytoplasmic death domain. | SIGNOR-59745 |
O43791 | O15164 | 1 | binding | down-regulates quantity by destabilization | 0.337 | Here, we analyzed changes in the ubiquitin landscape induced by prostate cancer-associated mutations of SPOP, an E3 ubiquitin ligase substrate-binding protein. SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. Of these, DEK and TRIM24 emerged as effector substrates consistently up-regulated by SPOP mutants. Up-regulation of DEK, TRIM24 and NCOA3 is a feature of prostate cancer SPOP mutations. | SIGNOR-272825 |
Q03431 | O75581 | 1 | binding | up-regulates | 0.337 | Parathyroid hormone (pth) binding to its receptor pth1r induces association of the pthpth1r complex with lrp6and phosphorylation of pppsp sites by protein kinase_ a, which in turn triggers wnt. | SIGNOR-199533 |
Q7Z6R9 | Q92186 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.337 | We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2 and the ST8SIA2 promoter.|We show that ST8SIA2 is induced by AP-2δ overexpression in chick retina. We use chromatin immunoprecipitation and gel shift assays to demonstrate direct interaction between AP-2δ and the ST8SIA2 promoter. | SIGNOR-268992 |
Q92830 | Q15796 | 1 | binding | up-regulates | 0.337 | Gcn5 functions like pcaf, in that it binds to tgf-beta-specific r-smads, and enhances transcriptional activity induced by tgf-beta. In addition, gcn5, but not pcaf, interacts with r-smads for bone morphogenetic protein (bmp) signalling pathways, and enhances bmp-induced transcriptional activity, suggesting that gcn5 and pcaf have distinct physiological functions in vivo. | SIGNOR-123315 |
Q9NVW2 | Q96MM3 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.337 | RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. | SIGNOR-269002 |
P49840 | Q2M1Z3 | 1 | phosphorylation | up-regulates activity | 0.337 | We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation. | SIGNOR-262878 |
Q9H0A0 | P04637 | 1 | acetylation | up-regulates quantity by stabilization | 0.337 | NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. | SIGNOR-272406 |
O75582 | P07101 | 1 | phosphorylation | up-regulates | 0.337 | Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax. studies on th from several species suggest that ser40 is the main site involved in direct activation of th | SIGNOR-95491 |
Q13315 | Q9BUR4 | 1 | phosphorylation | up-regulates activity | 0.337 | Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations. | SIGNOR-273511 |
Q01196 | P01106 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.337 | RUNX1 represses MYC expression through direct binding at three downstream enhancer elements | SIGNOR-260093 |
Q13177 | P01236 | 1 | phosphorylation | up-regulates | 0.337 | Phosphorylated form of prolactin has a higher affinity for heparin. | SIGNOR-186211 |
P01106 | P04818 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.337 | Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. | SIGNOR-267374 |
Q7Z6Z7 | P20226 | 1 | ubiquitination | down-regulates quantity | 0.337 | Having established that Huwe1 mediates TBP ubiquitination in vitro, we then asked which E2 conjugating enzymes work best with Huwe1 in this reaction.|Upregulation of Huwe1 expression during myogenesis induces TBP degradation and myotube differentiation. | SIGNOR-278696 |
A6ND36 | Q8N752 | 1 | binding | up-regulates quantity | 0.337 | We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates. | SIGNOR-273753 |
Q00535 | P30086 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.337 | Here, we demonstrate that RKIP is a substrate of cyclin-dependent kinase 5 (CDK5) in neurons and that the phosphorylation of RKIP at T42 causes the release of Raf-1. Moreover, T42 phosphorylation promotes the exposure and recognition of the target motif "KLYEQ" in the C-terminus of RKIP by chaperone Hsc70 and the subsequent degradation of RKIP via chaperone-mediated autophagy (CMA). | SIGNOR-276672 |
P31749 | P12755 | 1 | phosphorylation | down-regulates | 0.337 | The phosphorylation of ski at threonine 458 is induced by akt pathway activators including insulin, insulin-like growth factor-1, and hepatocyte growth factor. The phosphorylation of ski causes its destabilization and reduces ski-mediated inhibition of expression of another negative regulator of tgf-beta, smad7 | SIGNOR-252527 |
P04150 | P48775 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.337 | Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development. | SIGNOR-268995 |
P78368 | P84022 | 1 | phosphorylation | down-regulates | 0.337 | Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment. | SIGNOR-181069 |
P15882 | Q15078 | 1 | binding | up-regulates | 0.337 | _-chimaerin was identified to interact with the p35 activator of cdk5. The complex of _-chimaerin, cdk5 and p35 is enzymatically functional | SIGNOR-123439 |
Q7Z569 | Q9UNH5 | 1 | polyubiquitination | up-regulates activity | 0.337 | Brap2 promotes Lys-63 linked ubiquitination of HsCdc14A. Collectively, these results support the idea that Brap2 facilitates Lys-63 linked ubiquitin modification of HsCdc14A, which may not be targeted for degradation, but mainly for protein–protein interactions or other regulatory functions. | SIGNOR-271777 |
P27361 | Q13153 | 1 | phosphorylation | down-regulates | 0.337 | Activated erk can phosphorylate t292 in the prs, and this blocks the ability of pak to phosphorylate s298 and of rac-pak signaling to enhance mek1-erk complex formation. | SIGNOR-123074 |
P09603 | P15509 | 1 | binding | up-regulates | 0.337 | Granulocyte-macrophage colony-stimulating factor (gm-csf) is an important hematopoietic cytokine that exerts its effects by interaction with the gm-csf receptor (gmr) on the surface of responsive cells. The gm-csf receptor consists of two subunits: gmralpha, which binds gm-csf with low affinity, and gmrbeta, which lacks intrinsic ligand-binding capability but complexes with gmralpha to form a high-affinity receptor (gmralpha/beta). | SIGNOR-72455 |
P49841 | Q16584 | 1 | phosphorylation | up-regulates activity | 0.336 | Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ). | SIGNOR-279615 |
P12931 | P35790 | 2 | phosphorylation | up-regulates activity | 0.336 | We find that CHKA forms a complex with EGFR in a c-Src-dependent manner. Endogenous CHKA and EGFR co-immunoprecipitated from a variety of breast cancer cell lines and immortalized mammary epithelial cells. CHKA interacted with the EGFR kinase domain upon c-Src co-overexpression and was phosphorylated in a c-Src-dependent manner on Y197 and Y333. | SIGNOR-266350 |
P45983 | Q99640 | 1 | phosphorylation | up-regulates | 0.336 | A kinase assay using gst-myt1 revealed that active jnk1 or jnk3, but not jnk2, phosphorylated myt1 in vitro. | SIGNOR-183899 |
P12931 | P78357 | 1 | phosphorylation | down-regulates activity | 0.336 | If that is the case, then our genetic results support the notion that p190 is negatively regulated by both Src and integrin.|The Src family of tyrosine kinases phosphorylate mammalian p190. | SIGNOR-279572 |
P35637 | Q9UQ80 | 1 | sumoylation | up-regulates activity | 0.336 | Here, we show that Ebp1 p42 isoform can be sumoylated on both K93 and K298 residues, which mediate its nuclear translocation and are required for its anti-proliferative activity .. Hence, TLS-mediated sumoylation is required for Ebp1 transcriptional repressive activity. | SIGNOR-236904 |
Q16665 | P01584 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.336 | We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS. | SIGNOR-251718 |
Q8N5Z5 | Q9BT92 | 1 | binding | down-regulates quantity by destabilization | 0.336 | We have identified KCTD17 as a substrate-adaptor for Cul3-RING E3 ligases (CRL3s) that polyubiquitylates trichoplein. Depletion of KCTD17 specifically arrests ciliogenesis at the initial step of axoneme extension through aberrant trichoplein-Aurora-A activity. Thus, CRL3-KCTD17 targets trichoplein to proteolysis to initiate the axoneme extension during ciliogenesis. | SIGNOR-272463 |
P10586 | P00533 | 1 | dephosphorylation | down-regulates activity | 0.336 | Some 10 years ago, Hashimoto et al. (87) had shown that the LAR catalytic domain can dephosphorylate the EGFR receptor in vitro, and more recently, Kulas and colleagues (88) have demonstrated that the antisense mediated suppression of LAR can enhance the growth factor induced activation of EGFR in rat hepatoma cells.|These data indicate that LAR and RPTPsigma may have a significant role in GPCR induced EGFR signalling.Whereas in A431 cells LAR and RPTPsigma may act to suppress the EGFR in response to GPCR activation, it is possible that the converse may also be true in other cell types. | SIGNOR-277029 |
P35790 | P12931 | 2 | phosphorylation | down-regulates activity | 0.336 | Figure XREF_FIG shows that even though Chk phosphorylated Tyr 527 of Src to a level much lower than that of Csk, it was a much more efficient inhibitor of Src kinase activity.|These results suggest that Chk inhibited Src with a mechanism independent of Tyr-527 phosphorylation. | SIGNOR-279731 |
O15111 | O15350 | 1 | phosphorylation | up-regulates activity | 0.336 | IKK-alpha had an ability to stabilize p73 by inhibiting its polyubiquitination, and enhanced p73 mediated transcriptional activation as well as proapoptotic activity.|In addition, IKK-alpha phosphorylated the NH 2 -terminal portion of p73 and a kinase deficient mutant form of IKK-alpha had undetectable effect on p73. | SIGNOR-279697 |
Q13490 | Q01094 | 1 | ubiquitination | up-regulates activity | 0.336 | The ability of cIAP1 to promote wt E2F1 transcriptional activity was retained by all E2F1 mutants, except the K161R/164R mutant for which cIAP1 was completely inactive and the K185R whose basal transactivation activity was weakly enhanced by cIAP1 (XREF_FIG).|Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. | SIGNOR-278688 |
Q5T447 | Q14790 | 1 | polyubiquitination | down-regulates activity | 0.336 | HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains at K215. | SIGNOR-272077 |
P51812 | P04637 | 1 | phosphorylation | up-regulates activity | 0.336 | Here we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53 (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus. | SIGNOR-279567 |
Q4G148 | Q04721 | 1 | binding | up-regulates | 0.336 | We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum. | SIGNOR-177694 |
P68400 | P11473 | 1 | phosphorylation | up-regulates | 0.336 | Casein kinase ii (ckii) phosphorylates vdr both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of vdr to bind dna, but increases its ability to transactivate target promoters | SIGNOR-153711 |
Q8TEU7 | P01112 | 1 | guanine nucleotide exchange factor | up-regulates | 0.336 | Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras. | SIGNOR-183796 |
P07550 | P50148 | 1 | binding | up-regulates activity | 0.336 | 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-257081 |
P12931 | Q8IXH7 | 1 | phosphorylation | down-regulates activity | 0.336 | Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. | SIGNOR-276402 |
O75914 | Q9UM54 | 1 | phosphorylation | up-regulates activity | 0.336 | P21-activated kinase 3 phosphorylated myosin VI, and the site was identified as Thr(406). The phosphorylation of myosin VI significantly facilitated the actin-translocating activity of myosin VI. | SIGNOR-250244 |
Q05655 | P15941 | 1 | phosphorylation | up-regulates | 0.336 | We show that phosphorylation of muc1 by pkcdelta increases binding of muc1 and beta-catenin in vitro and in vivo. The functional significance of the muc1-pkcdelta interaction is further supported by the demonstration that mutation of the pkcdelta phosphorylation site abrogates muc1-mediated decreases in binding of beta-catenin to e-cadherin | SIGNOR-115501 |
Q13315 | O43504 | 1 | phosphorylation | up-regulates activity | 0.336 | Strikingly, we found that the kinase ataxia telangiectasia mutated (ATM) phosphorylated HBXIP at Ser (108).|The knockdown of ATM by siRNA remarkably decreased the levels of serine phosphorylation and blocked the nuclear import of HBXIP. | SIGNOR-279791 |
P48736 | Q01105 | 1 | phosphorylation | up-regulates activity | 0.336 | We show that PI3Kgamma phosphorylates I2PP2A on serine 9 and 93 residues resulting in enhanced interaction of I2PP2A with PP2A. | SIGNOR-278320 |
Q86T82 | Q9UM11 | 1 | binding | down-regulates activity | 0.336 | Here we show that USP37 binds the APC/C coactivator CDH1|Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry | SIGNOR-265054 |
Q00535 | P06400 | 1 | phosphorylation | down-regulates | 0.336 | Phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a cdk5 inhibitor, roscovitine, which does not inhibit the usual rb cyclin-d kinases cdk4 and cdk6. Furthermore, analyses of levels and subcellular localization of cdk-related cyclins did not reveal any change following cdk5 activation, arguing for a direct effect of cdk5 activity on rb protein. Rb phosphorylation was visualized using phosphorylation-dependent antibodies (p-rbser795 and p-rbser807/811). | SIGNOR-134468 |
P00519 | Q06187 | 1 | phosphorylation | down-regulates activity | 0.336 | In this report we describe for the first time that ABL1 and Btk physically interact and that ABL1 can phosphorylate tyrosine 223 in the SH3 domain of Btk. | This is presumably due to the negative regulatory effectof Btk SH3 domain phosphorylation caused by ABL1,which would result in a decreased catalytic activity ofBtk resulting in impaired autophosphorylation. | SIGNOR-260801 |
Q15418 | Q8IX03 | 1 | phosphorylation | up-regulates | 0.335 | Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2. | SIGNOR-203298 |
P48736 | P07951 | 1 | phosphorylation | up-regulates activity | 0.335 | Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization. | SIGNOR-263028 |
P18031 | P12814 | 1 | dephosphorylation | up-regulates | 0.335 | Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase. | SIGNOR-141634 |
Q00535 | Q00536 | 1 | phosphorylation | up-regulates activity | 0.335 | Taken together, our findings demonstrate that Pctaire1 interacts with p35, both in vitro and in vivo, and that phosphorylation of Pctaire1 by Cdk5 enhances its kinase activity. | SIGNOR-279149 |
Q13153 | Q92934 | 1 | phosphorylation | down-regulates | 0.335 | Pak phosphorylates bad in vitro and in vivo on ser112 and ser136, resulting in a markedly reduced interaction between bad and bcl-2 or bcl-x(l) and the increased association of bad with 14-3-3tau. | SIGNOR-73533 |
Q15418 | P49427 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.335 | RSK1 phosphorylated Thr162 on UBE2R1.RSK1 induced self-ubiquitination and destabilisation of UBE2R1 by phosphorylation. | SIGNOR-277330 |
P07737 | P55283 | 1 | null | up-regulates activity | 0.335 | Taken together, data obtained from MCF10A cells were consistent with the idea that Rho signaling to Dia1 and profilin-1 was essential for R-cadherin adherens junction formation. | SIGNOR-253111 |
Q9H4B4 | P60484 | 1 | phosphorylation | down-regulates activity | 0.335 | Plk3 phosphorylates pten on thr-366 and ser-370. Plk3-mediated phosphorylation facilitates pten stabilization, thereby negatively regulating the pi3k/pdk1/akt1 signaling axis | SIGNOR-168473 |
Q9H422 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.335 | We show that Yak1 directly phosphorylates Hsf1 in vitro, leading to the increase in DNA binding activity of Hsf1. | SIGNOR-279054 |
Q16620 | O43639 | 1 | binding | up-regulates | 0.335 | We identified the nck2 adaptor protein as a novel interaction partner of the active form of trkb. Additionally, we identified three tyrosines in icd-trkb (y694, y695, and y771) that are crucial for this interaction. | SIGNOR-89764 |
P17612 | P09917 | 1 | phosphorylation | down-regulates activity | 0.335 | These results indicate that PKA phosphorylates 5-LO on Ser-523, which inhibits the catalytic activity of 5-LO and reduces cellular LT generation. | SIGNOR-264410 |
P02452 | Q08345 | 1 | binding | up-regulates activity | 0.335 | The Discoidin Domain Receptors (DDRs) constitute a unique set of receptor tyrosine kinases that signal in response to collagen.|Consistent with this view128, we showed that ectopic expression of DDR1b or DDR2 in HT1080 cells elicited a potent growth inhibitory effect only when the cells were cultured on 2D or 3D COL1 matrices, in agreement with previous studies in melanoma48, breast cancer76,78, and lung cancer cells74,75. | SIGNOR-272340 |
P31749 | Q9UBP6 | 1 | phosphorylation | down-regulates | 0.335 | The trna methylase mettl1 is phosphorylated and inactivated by pkb and rsk in vitro and in cells | SIGNOR-24994 |
Q92481 | P04637 | 1 | binding | up-regulates quantity by stabilization | 0.335 | These data suggest that AP-2β enhances transactivation of p53 and regulates CRYAB transcription via p53. Further study demonstrated that AP-2β interacts with p53 and augments its protein stability. Taken together, our results indicate that AP-2β up-regulates the transcription of the CRYAB gene through stabilizing p53. | SIGNOR-255422 |
P17252 | P17844 | 1 | phosphorylation | down-regulates activity | 0.335 | We report that p68 is phosphorylated by protein kinase C in vitro and binds calmodulin in a Ca(2+)-dependent manner. Both phosphorylation and calmodulin binding inhibited p68 ATPase activity | In addition, a 20-amino acid peptide corresponding to residues 549-568 of p68 was phosphorylated in a Ca- and phospholipid-dependent manner hy PKC | SIGNOR-248896 |
P30542 | P19086 | 1 | binding | up-regulates activity | 0.335 | 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-257092 |
P24941 | Q9UGP5 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.335 | Phosphorylation of DNA polymerase λ is required to maintain its stability. Recently, we identified Pol lambda as an interaction partner of cyclin-dependent kinase 2 (CDK2) that is central to the cell cycle G1/S transition and S-phase progression. Experiments with phosphorylation-defective mutants suggest that phosphorylation of Thr 553 is important for maintaining Pol lambda stability, as it is targeted to the proteasomal degradation pathway through ubiquitination unless this residue is phosphorylated. | SIGNOR-276169 |
Q06187 | P51813 | 1 | phosphorylation | up-regulates | 0.335 | Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. | SIGNOR-98028 |
P68400 | P30519 | 1 | phosphorylation | up-regulates activity | 0.335 | Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. | CK2 activation is abolished by the S79A mutation but preserved in S179A and T248A mutations, indicating that S79 is the target of CK2-dependent activation of HO2 | SIGNOR-250895 |
P55317 | Q14938 | 1 | binding | up-regulates | 0.335 | Androgen receptor (ar) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between ar and forkhead box (fox) transcription factors, particularly foxa1./ Foxa1 is capable of bringing ar and nfix into proximity, indicating that foxa1 facilitates the ar and nfi interaction by bridging the complex. | SIGNOR-205082 |
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