IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P05771 | P06730 | 1 | phosphorylation | up-regulates | 0.348 | Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E . | SIGNOR-248946 |
P06493 | P30622 | 1 | phosphorylation | up-regulates activity | 0.49 | Cdc2 phosphorylates T287|CLIP-170, the founding member of microtubule “plus ends tracking” proteins, is involved in many critical microtubule-related functions, including recruitment of dynactin to the microtubule plus ends and formation of kinetochore-microtubule attachments during metaphase. |These results demonstrate that Cdc2-mediated phosphorylation of CLIP-170 is essential for the normal function of this protein during cell cycle progression. | SIGNOR-275470 |
P17612 | O00418 | 1 | phosphorylation | up-regulates activity | 0.305 | EEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca(2+)/calmodulin (CaM)-independent eEF-2K activity. sites of phosphorylation were Ser-365 and Ser-499 | SIGNOR-250354 |
P00740 | P03951 | 0 | cleavage | up-regulates activity | 0.484 | Factor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX.|The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets. | SIGNOR-263537 |
Q9UH03 | Q13976 | 0 | phosphorylation | up-regulates activity | 0.2 | Mutation of Ser-91 to Ala in recombinant Sept3 also abolished PKG phosphorylation, confirming that Ser-91 is the major site in vitro. Therefore Sept3 is phosphorylated on Ser-91 in nerve terminals and its phosphorylation may contribute to the regulation of its subcellular localization in neurons. | SIGNOR-263183 |
P17612 | P19429 | 1 | phosphorylation | up-regulates activity | 0.423 | Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction. | SIGNOR-134605 |
Q96GD4 | O60879 | 1 | phosphorylation | up-regulates | 0.288 | The microtubule binding fh2 domain of mdia3 is phosphorylated by aurora b kinase in vitro, and cells expressing the nonphosphorylatable mdia3 mutant cannot position chromosomes at the metaphase plate | SIGNOR-172803 |
Q9UER7 | P68400 | 0 | phosphorylation | up-regulates | 0.327 | Daxx-sim is phosphorylated by ck2 kinase at residues s737 and s739. Phosphorylation promotes daxx-sim binding affinity toward sumo-1 over sumo-2/3, causing daxx preference for sumo-1 conjugation and interaction with sumo-1-modified factors. | SIGNOR-173105 |
P12931 | Q96P31 | 1 | phosphorylation | up-regulates activity | 0.2 | Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2. | SIGNOR-274008 |
P46531 | Q9Y5J3 | 1 | 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 |
Q8NF50 | P60953 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.767 | Recently, DOCK8 was identified as a guanine-nucleotide exchange factor (GEF) for Cdc42 activation and has been associated with human mental retardation. | SIGNOR-268412 |
P35222 | P12931 | 0 | phosphorylation | down-regulates activity | 0.761 | beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation. | SIGNOR-106458 |
P08237 | P01106 | 0 | transcriptional regulation | up-regulates quantity | 0.327 | C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | SIGNOR-259988 |
Q92597 | P11309 | 0 | phosphorylation | down-regulates activity | 0.2 | Collectively, we find that PIM1 expression leads to increased levels of NDRG1 pS330, and PIM1 dependent NDRG1 phosphorylation decreases NDRG1 protein stability.|NDRG1 is phosphorylated by PIM1 at serine 330 (pS330), and the level of NDRG1 pS330 is associated higher grade prostate tumors. | SIGNOR-279308 |
Q8TD08 | P67775 | 0 | dephosphorylation | down-regulates | 0.289 | Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20% | SIGNOR-142977 |
Q01105 | Q9BZL6 | 0 | phosphorylation | down-regulates activity | 0.2 | In conclusion, the roles of protein kinase D2 and its substrate SET in T cell activation were investigated and we found that protein kinase D2 phosphorylates Ser171 of SET, which resulted in the reduction of its inhibitory effect on PP2A phosphatase activity. | SIGNOR-279560 |
P08631 | Q99062 | 1 | phosphorylation | up-regulates activity | 0.385 | Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. the ability of Hck to phosphorylate the G-CSF-R in vitro, both Y728 and Y763 fit the Src consensus phosphorylation site. we investigated the activation of Hck by the G-CSF-R in intact cells as well as in vitro. These studies revealed recruitment of Hck to activated G-CSF-R, mediated by direct binding via its SH2 domain to multiple phosphotyrosines of the receptor. In addition, we show that Hck becomes activated upon G-CSF treatment and is, in turn, able to phosphorylate the G-CSF-R, indicating a clear functional and physical involvement in G-CSF signaling. | SIGNOR-251264 |
Q99683 | Q96HS1 | 0 | dephosphorylation | up-regulates activity | 0.437 | PGAM5 Is a Protein Ser/Thr Phosphatase That Activates ASK1. PGAM5 Dephosphorylates ASK1. This dephosphorylation unleashes phosphorylation ofThr-838 in the kinase domain, with activation of ASK1. | SIGNOR-277984 |
P17676 | P21291 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We conclude that c-Rel regulates CRP expression without the requirement of binding to a kappaB site, and binds directly to C/EBPbeta to facilitate the binding of C/EBPbeta to the CRP promoter | SIGNOR-254049 |
P06493 | O43148 | 1 | phosphorylation | up-regulates activity | 0.255 | We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. | SIGNOR-265501 |
Q96PU5 | O00141 | 0 | phosphorylation | down-regulates activity | 0.787 | Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1. | SIGNOR-263076 |
P31751 | Q7Z6J0 | 1 | phosphorylation | down-regulates | 0.389 | Overexpression of posh induces apoptosis in a variety of cell types, but apoptosis can be prevented by co-expressing the pro-survival protein kinase akt. We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac | SIGNOR-155233 |
Q01094 | P32780 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.434 | TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase. E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase. | SIGNOR-251260 |
P48506 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.47 | In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs). | SIGNOR-256277 |
Q96J02 | Q15303 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.606 | Itch catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into intracellular vesicles, and stimulated degradation of ErbB4 CYT-1 | SIGNOR-271416 |
Q13535 | Q9NVI1 | 1 | phosphorylation | up-regulates activity | 0.623 | Alternatively, the locally accumulated ATRIP-ATR might have sufficient activity to phosphorylate FANCI without TOPBP1 stimulation.|The results described above and our previous studies clearly indicated that FANCI phosphorylation is mediated by ATR kinase in a manner dependent on the FA core complex and FANCD2 protein. | SIGNOR-279320 |
P22681 | P17252 | 0 | phosphorylation | down-regulates quantity | 0.322 | However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway. | SIGNOR-249056 |
P78545 | Q13153 | 0 | phosphorylation | up-regulates | 0.456 | Phosphorylation-dependent regulation of stability and transforming potential of ets transcriptional factor ese-1 by p21-activated kinase 1. Pak1 selectively phosphorylates ese-1 at ser(207). Intriguingly, pak1 phosphorylation inactive mutant ese1-s207a is more unstable | SIGNOR-154743 |
P01106 | Q9Y4L5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.448 | These results suggest that Rabring7 antagonizes function of c-Myc possibly through degradation of c-Myc.|Unexpectedly, we found that Rabring7 more strongly binds to c-Myc than to MM-1 (XREF_FIG) and that Rabring7 stimulates poly-ubiquitination of c-Myc in a T58 dependent manner (XREF_FIG). | SIGNOR-278662 |
Q13131 | Q8N122 | 1 | phosphorylation | down-regulates activity | 0.687 | Ampk in turn inactivates mtorc1 directly by phosphorylating raptor and indirectly by phosphorylating tsc2. | SIGNOR-173035 |
P35613 | Q9HC98 | 0 | phosphorylation | down-regulates activity | 0.2 | These results indicate that NEK6 directly interacts with CD147 and phosphorylates the protein at serine-252 in Huh-7 cells. | SIGNOR-273882 |
O60260 | Q8IXI2 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We observe that Parkin efficiently ubiquitylates Miro1 at highly conserved lysine residues, 153, 230, 235, 330 and 572, upon phosphorylation by PINK1. | SIGNOR-278561 |
Q13131 | P29474 | 1 | phosphorylation | up-regulates | 0.283 | The central finding of this report is that rosiglitazone rapidly stimulates no production and enos ser-1177 phosphorylation in an ampk-dependent manner | SIGNOR-160838 |
P46531 | P11309 | 0 | phosphorylation | up-regulates activity | 0.27 | Interestingly, Pim1 phosphorylated Notch1 and Notch3, but not Notch2 ICD (Figure xref ), which was in line with the observed Pearson correlations ( xref ).|Our data indicate that endogenous Pim1 and Notch1 interact already in the cytoplasm, which supports the notion that Pim1 enhances nuclear localization and activity of Notch1. | SIGNOR-279643 |
Q16665 | Q13315 | 0 | phosphorylation | up-regulates | 0.432 | Here we show that hypoxia results in ataxia telangiectasia mutated (atm)-dependent phosphorylation of hypoxia-inducible factor 1-alpha (hif-1_) on serine(696) and mediates downregulation of mtorc1 signaling. phosphorylation of hif-1_ by atm is required for its stability | SIGNOR-169999 |
Q9UGP5 | P24941 | 0 | 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 |
P31749 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.405 | Mass spectrometry showed that AKT1 also phosphorylated HSF1 at T142, S230 and T527 in addition to S326, whereas the other kinases did not. Subsequent investigation revealed that phosphorylation at T142 is necessary for HSF1 trimerization and that S230, S326 and T527 are required for HSF1 gene transactivation and recruitment of TFIIB and CDK9. | SIGNOR-277579 |
Q92823 | P29323 | 0 | phosphorylation | up-regulates activity | 0.298 | EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase. | SIGNOR-262863 |
O15259 | P68400 | 0 | phosphorylation | up-regulates | 0.2 | Casein kinase 2 (ck2)-mediated phosphorylation of three critical serine residues within a cluster of acidic amino acids in nephrocystin mediates pacs-1 binding, and is essential for colocalization of nephrocystin with pacs-1 at the base of cilia. Inhibition of ck2 activity abrogates this interaction and results in the loss of correct nephrocystin targeting. | SIGNOR-142343 |
P68400 | P61244 | 1 | phosphorylation | down-regulates | 0.361 | Here, we have mapped the nh2-terminal in vivo phosphorylation sites of max to ser2 and ser11[...] | SIGNOR-35772 |
Q14457 | P46934 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.46 | BECN1 stability was increased by NEDD4 via K6 and K27 ubiquitination during autophagy induction, thereby promoting autophagy activation.|Further, NEDD4 mediated K6- and K27- linkage ubiquitination of BECN1, leading to elevated stability of BECN1 and increased autophagy. | SIGNOR-278558 |
P17535 | P27361 | 0 | phosphorylation | up-regulates | 0.459 | Menin binds the jun family transcription factor jund and inhibits its transcriptional activity. The menin-jund interaction blocks jun n-terminal kinase (jnk)-mediated jund phosphorylation and suppresses jund-induced transcription. We found a role for phosphorylation of the ser100 residue of jund;jund phosphorylation were prevented by inhibitors of calcium, calmodulin, or erk1/2 kinase. | SIGNOR-196034 |
Q96Q89 | P06493 | 0 | phosphorylation | up-regulates activity | 0.41 | Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1. | SIGNOR-262695 |
P18848 | Q5JTZ9 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.244 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269415 |
A8MYZ6 | P31749 | 0 | phosphorylation | down-regulates | 0.648 | The phosphorylation of the two remaining akt-dependent sites inhibits foxo6 transcriptional activity | SIGNOR-252582 |
P20962 | P04150 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.328 | Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner | SIGNOR-268460 |
P06239 | P10747 | 1 | phosphorylation | up-regulates | 0.754 | We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor | SIGNOR-45524 |
Q32MZ4 | P00533 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.293 | GC-binding factor 2 (GCF2) is a transcriptional repressor that decreases activity of the epidermal growth factor receptor (EGFR) and other genes. |Deletion mutants of GCF2 revealed that amino acids 429–528 are required for both DNA binding and repression of the EGFR promoter. | SIGNOR-266057 |
Q00975 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.317 | Here, we report a direct modulation of ca(v)2.2 channel inactivation properties by 14-3-3, a family of signaling proteins involved in a wide range of biological processes.Wild-type gst fusion proteins containing the putative 14-3-3-binding motif (aa 2076__?2140) werein vitro phosphorylated at s2126 by either camkii or pka, as detected by thesequence- and phosphorylation-specific antibody, anti-ps2126 (middle panel). Phosphorylation of s2126 significantly increases its binding to recombinant 14-3-3? | SIGNOR-149684 |
P53778 | P52564 | 0 | phosphorylation | up-regulates | 0.659 | Mapkk6 was shown to phosphorylate and specifically activate the p38/mpk2 sub of the mitogen-activated protein kinase superfamily . the p38 mapkinasekinasemkk6 is identified as a common activator of p38 alpha, p38 beta 2, and p38 gamma mapkinaseisoforms . p38mapks are activated by dual phosphorylation on a t-x-y motif in the activation loop through the action of map kinase kinases | SIGNOR-184134 |
P08151 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.514 | Here, we have used an in vitro kinase assay and phospho-peptide mass spectrometry analysis to identify site(s) of direct phosphorylation of GLI1 by DYRK1A and have determined that DYRK1A phosphorylates GLI1 at Ser408 within its nuclear localization sequence.|The kinase DYRK1A (dual-specificity tyrosine phosphorylation regulated kinase 1a) has been shown to activate GLI1 via a phosphorylation event, leading to the translocation of GLI1 from the cytoplasm to the nucleus . | SIGNOR-278930 |
P17252 | O75144 | 1 | phosphorylation | up-regulates activity | 0.2 | PKCα and PKCβ are required for phosphorylation of ICOSL and ICOSL-mediated cytokine induction. Therefore, S285 is required for PKC substrate (serine) phosphorylation of ICOSL, and each of the upstream arginines is similarly required for this phosphorylation. | SIGNOR-273798 |
O96017 | P38398 | 1 | phosphorylation | up-regulates | 0.787 | In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites. | SIGNOR-120575 |
Q96GD4 | Q12834 | 1 | phosphorylation | down-regulates activity | 0.767 | When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase promoting complex and cyclosome (APC/C).|When SAC is active, Aurora kinase B (AurkB) phosphorylates and inactivates CDC20, to prevent the activation of anaphase-promoting complex/cyclosome (APC/C) (Hagting et al., xref ; Nasmyth, xref ; Ruchaud et al., xref ). | SIGNOR-280190 |
P10242 | Q86Z02 | 0 | phosphorylation | down-regulates activity | 0.2 | C-Myb appears to be phosphorylated by HIPK1 in its negative regulatory domain as supported by both in vivo and in vitro data. | SIGNOR-279189 |
O75925 | P68400 | 0 | phosphorylation | up-regulates | 0.332 | Ck2 phosphorylates serine residues adjacent to the sim of pias1 these findings show that the phosphosim module mediates binding to free sumo and sumo conjugates in a phosphorylation-dependent mode, with ck2 being the critical kinase involvedin this process. | SIGNOR-184047 |
Q9HAW8 | P20823 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.251 | Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter. | SIGNOR-253971 |
P30307 | O14757 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.85 | The signal for ubiquitination after uv and ir exposure is created by phosphorylation of cdc25a mediated by chk1 and chk2, respectively. Chk1 is a major kinase phosphorylating cdc25a (ser76/124) and cdc25c (ser216). | SIGNOR-163158 |
Q16828 | P45983 | 1 | dephosphorylation | down-regulates activity | 0.632 | Our data demonstrate MKP-3 has differential substrate preference in astrocytes compared to other cells types, since it preferentially dephosphorylated p-JNK over p-ERK.|The main findings of our studies are (1) MKP-3 preferentially reduces p-JNK over p-ERK and p-p38 in primary astrocytes; (2) This MAPK modulation pattern in primary astrocytes significantly reduced NO and completely abolished IL-6 and TNF accumulation; and (3) These effects are specifically induced by MKP-3 since block-age of MKP-3 mRNA expression reversed its action on MAPKs and pro-inflammatory mediators in BV-2 microglia cells. | SIGNOR-277150 |
P28482 | O15067 | 1 | phosphorylation | up-regulates | 0.2 | T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation. | SIGNOR-267306 |
P17600 | O75914 | 0 | phosphorylation | up-regulates activity | 0.334 | Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release | SIGNOR-250246 |
Q16539 | P06239 | 0 | phosphorylation | up-regulates activity | 0.475 | Lck, Fyn, and Zap70 activate p38 even in the absence of Tyr182 phosphorylation.p38 is a substrate for Fyn, Lck and Zap70.Thus, T cell Src family kinases and Zap70 activate p38 by phosphorylating Tyr323. | SIGNOR-276029 |
O75962 | Q05397 | 0 | phosphorylation | up-regulates activity | 0.509 | A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity. | SIGNOR-249188 |
P49841 | P04198 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.33 | Because GSK3\u03b2 phosphorylates Nmyc at T58, we assessed GSK3\u03b2 activation in Dex-treated MB cells. | SIGNOR-279722 |
Q99942 | Q9P055 | 1 | ubiquitination | down-regulates activity | 0.509 | RNF5 is a ubiquitin ligase anchored to the ER membrane implicated in ERAD via ubiquitination of misfolded proteins. This association results in Ubc13-dependent RNF5-mediated noncanonical ubiquitination of JAMP. This ubiquitination does not alter JAMP stability but rather inhibits its association with Rpt5 and p97. | SIGNOR-271483 |
O00257 | Q9H2X6 | 0 | phosphorylation | up-regulates activity | 0.423 | In addition, HIPK2 phosphorylates Pc2 at several sites, including threonine 495. | SIGNOR-278484 |
Q15418 | P50552 | 1 | phosphorylation | down-regulates | 0.45 | Rsk1 phosphorylated vasp on t278, a site regulating its binding to actin. | SIGNOR-172899 |
P37231 | P60484 | 1 | null | down-regulates activity | 0.456 | The PAX8-PPARγ rearrangement leads to strong induction of the PPARγ protein and the consequent abrogation of the normal PPARγ function. PPARγ overexpression abolishes the PTEN-inhibitory effect on immunoactive AKT, which in turn induces the PI3K signaling pathway. | SIGNOR-251997 |
Q14449 | Q02763 | 0 | phosphorylation | up-regulates activity | 0.65 | Together these results suggest a role for the Grb14 SH2 domain in Tie2 mediated Grb14 signaling.|Tyrosine phosphorylation of Grb14 by Tie2. | SIGNOR-279300 |
P11912 | Q9NRF2 | 0 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 is recruited by the phosphorylated ITIM-bearing receptors such as CD22 and it dephosphorylates proximal BCR signaling molecules such as CD79, SYK, BLNK. | SIGNOR-268457 |
Q9UQ13 | P17252 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | PKCalpha/delta phosphorylate Sur8 at Thr-71 and Ser-297, respectively. This phosphorylation is essential for polyubiquitin-dependent degradation of Sur8. | SIGNOR-275568 |
P17861-2 | Q09472 | 0 | acetylation | up-regulates quantity by stabilization | 0.285 | P300 increases the acetylation and protein stability of XBP1s, and enhances its transcriptional activity, whereas SIRT1 deacetylates XBP1s and inhibits its transcriptional activity.. The mRNA encoding the active spliced form of XBP1 (XBP1s) is generated from the unspliced form by IRE1 (inositol-requiring enzyme 1) during the UPR. | SIGNOR-260429 |
Q9Y4G8 | Q9NYY3 | 0 | phosphorylation | up-regulates activity | 0.357 | Here, we report that Plk2 phosphorylates a quartet of Ras and Rap regulators : SynGAP, PDZGEF1, RasGRF1 and SPAR, resulting in powerful bidirectional control over Rap and Ras activity.|Thus, Plk2 was sufficient to promote the activities of both SynGAP and PDZGEF1 in mammalian cells. | SIGNOR-280066 |
P60953 | Q7Z6I6 | 0 | gtpase-activating protein | down-regulates activity | 0.458 | 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-260487 |
P49840 | P05129 | 0 | phosphorylation | down-regulates | 0.324 | Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway. | SIGNOR-115726 |
Q02156 | Q8NER1 | 1 | phosphorylation | up-regulates activity | 0.2 | We found that mutation of S800 to alanine significantly reduced the PMA-induced enhancement of capsaicin-evoked currents and the direct activation of TRPV1 by PMA. Mutation of S502 to alanine reduced PMA enhancement of capsaicin-evoked currents, but had no effect on direct activation of TRPV1 by PMA. Conversely, mutation of T704 to alanine had no effect on PMA enhancement of capsaicin-evoked currents but dramatically reduced direct activation of TRPV1 by PMA. | SIGNOR-249232 |
Q9Y657 | O14965 | 0 | phosphorylation | up-regulates activity | 0.243 | The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. | SIGNOR-273550 |
P31749 | Q13043 | 1 | phosphorylation | down-regulates | 0.397 | Akt interacts with mst1 and phosphorylates a highly conserved residue threonine 120 of mst1, which leads to inhibition of its kinase activity and nuclear translocation as well as the autophosphorylation of thr(183). | SIGNOR-252507 |
P0C6X7-PRO_0000037311 | Q9Y4K3 | 1 | deubiquitination | down-regulates activity | 0.2 | Also, SARS-CoVPLPro catalyzed deubiquitination ofTNF-receptor-associatedfactor3(TRAF3)and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist | SIGNOR-260248 |
Q9NRC8 | P62826 | 1 | deacetylation | down-regulates activity | 0.2 | N this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. |The nuclear export by CRM1 requires an interaction with the small GTPase Ras-related nuclear antigen (Ran), which cycles between GTP- and GDP-bound states. The binding of Ran GTP to CRM1 in the nucleus increases the affinity of CRM1 for cargo proteins [[18], [19], [20]]. Interestingly, Ran is a lysine-acetylated protein | SIGNOR-275849 |
P0DP25 | P06213 | 0 | phosphorylation | down-regulates | 0.375 | The in vitro phosphorylation of calmodulin by the insulin receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule. | SIGNOR-266336 |
P07947 | P11802 | 1 | phosphorylation | down-regulates | 0.254 | We purified tyrosine 17 kinases from hela cells and found that the src family non-receptor tyrosine kinase c-yes contributes a large fraction of the tyrosine 17 kinase activity in hela lysatesthis site is equivalent to tyrosine 15 of cyclin dependent kinase 1, which undergoes inhibitory phosphorylation by wee1 and myt1 | SIGNOR-178624 |
Q8IXJ9 | P42771 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.3 | Modeling ASXL1 mutation revealed impaired hematopoiesis caused by derepression of p16Ink4a through aberrant PRC1-mediated histone modification. These results indicated that loss of protein interaction between Asxl1 mutant and Bmi1 affected the activity of PRC1, and subsequent derepression of p16Ink4a by aberrant histone ubiquitination could induce cellular senescence, resulting in low-risk MDS-like phenotypes in Asxl1G643fs/+ mice. | SIGNOR-260119 |
Q9UKB1 | O00418 | 1 | ubiquitination | down-regulates | 0.436 | Eef2k was degraded by the ubiquitin-proteasome system through the ubiquitin ligase scf(__trcp) (skp1-cul1-f-box protein, __-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eef2k on a canonical __trcp-binding domain | SIGNOR-197730 |
P40189 | O60674 | 1 | phosphorylation | up-regulates activity | 0.639 | All IL-6-type cytokines recruit gp130to their receptot complexes They either signal via gp130 alone [8] or in combination with LIFR [9] or the recently cloned OSMR [10], which are all able to activate Jaks proteins. Two tyrosine residues at the corresponding positions of Jak2 (tyrosine-1007 and tyrosine-1008) were found to be phosphorylated, and a single mutation of tyrosine-1007 eliminated essentially all tyrosine kinase activity [59]. | SIGNOR-238634 |
P49841 | O15169 | 1 | phosphorylation | up-regulates activity | 0.92 | Axin residues T609 and S614 are physiological GSK3beta targets. Axin phosphorylation in the regulation of b-catenin stability. When active (left), GSK3b phosphorylates Axin as well as APC and b-catenin. The phosphorylated form of Axin binds strongly to b-catenin and promotes the phosphorylation of b-catenin by GSK3b, leading to strong interaction with b-TrCP | SIGNOR-251221 |
P07948 | Q7L591 | 1 | phosphorylation | up-regulates activity | 0.409 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268447 |
Q96RG2 | P49841 | 1 | phosphorylation | down-regulates activity | 0.288 | In vitro, PASK directly phosphorylates GSK3\u03b2 on its inactivating phosphorylation site Ser(9).|We conclude that PASK phosphorylates and inactivates GSK3\u03b2, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3\u03b2-mediated PDX-1 protein degradation in pancreatic \u03b2-cells. | SIGNOR-279639 |
P23470 | P51813 | 1 | dephosphorylation | down-regulates activity | 0.26 | 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-254693 |
P60953 | Q96N67 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.739 | As a GEF, Dock7 exchanges GDP for GTP on Cdc42 and Rac1, causing their activation, followed by activation of downstream effectors, including the dephosphorylation (activation) of cofilin, a key regulator of actin turnover. | SIGNOR-261886 |
O60260 | Q96M98 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | In this study, we found that CHIP promotes Parkin-mediated Pael-R ubiquitination and subsequent degradation. In vitro ubiquitination assays suggested that only a combination of both Parkin and its cofactor CHIP function as a ubiquitin ligase, which is able to sufficiently ubiquitinate Pael-R in vivo (Figure 6). | SIGNOR-272889 |
P24385 | O15111 | 0 | phosphorylation | down-regulates | 0.379 | Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286. | SIGNOR-139570 |
P31260 | Q15746 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively | SIGNOR-261643 |
Q9H0M0 | Q9BT67 | 1 | ubiquitination | down-regulates quantity | 0.381 | Accordingly, the ubiquitination assays were performed and the results revealed that knockdown of WWP1 reduced the ubiquitination of NDFIP1 in HuCCT1 and vice versa in HCCC-9810 and RBE (Fig. 7E).|In addition, we found that WWP1 could reduce the protein level of NDFIP1 via ubiquitination. | SIGNOR-278796 |
Q92922 | Q86X55 | 0 | methylation | up-regulates activity | 0.537 | CARM1-mediated BAF155 methylation affects gene expression by directing methylated BAF155 to unique chromatin regions (e.g., c-Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155 acquires tumorigenic functions via arginine methylation. | SIGNOR-251708 |
O75143 | P42345 | 0 | phosphorylation | down-regulates | 0.651 | Mtor phosphorylates a mammalian homologue of atg13 and the mammalian atg1 homologues ulk1 and ulk2. | SIGNOR-183965 |
P54646 | Q53ET0 | 1 | phosphorylation | down-regulates | 0.489 | Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2 | SIGNOR-142211 |
Q07912 | Q9Y4C1 | 1 | phosphorylation | down-regulates activity | 0.37 | We report that ACK1 phosphorylates the ER co-activator, KDM3A, a H3K9 demethylase, at an evolutionary conserved tyrosine 1114 site in a heregulin-dependent manner, even in the presence of tamoxifen. | SIGNOR-276842 |
Q7LBC6 | P25874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. | SIGNOR-266638 |
P17612 | O14813 | 1 | phosphorylation | down-regulates | 0.307 | Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription. | SIGNOR-186462 |
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