IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P08047 | P24941 | 0 | phosphorylation | up-regulates activity | 0.423 | Mutation of Sp1 Ser59 abrogates the cyclin ACDK augmentation of Sp1-dependent transcriptional transactivation | SIGNOR-248232 |
P00519 | Q13535 | 1 | phosphorylation | up-regulates | 0.599 | C-abl can phosphorylate atr on y291 and y310 and this phosphorylation appears to have a positive role in atr activation under genotoxic stress. | SIGNOR-167632 |
P04150 | P49841 | 0 | phosphorylation | down-regulates activity | 0.54 | We found hormone-dependent GR phosphorylation on serine 404 by GSK-3beta [ ]Cells expressing a GR that is incapable of GSK-3beta phosphorylation had a redirection of the global transcriptional response to hormone, including the activation of additional signaling pathways, in part due to the altered ability of unphosphorylatable GR to recruit transcriptional cofactors CBP/p300 and the p65 (RelA) subunit of NF-kappaB | SIGNOR-181541 |
P49137 | Q00987 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.364 | Hdm2 phosphorylation by mapkap kinase 2 enhances hdm2 activity and promote the degradation of p53. | SIGNOR-133560 |
Q7L7L0 | O75582 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that MSK1 phosphorylated histone H2A on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by MSK1. Furthermore, we found that acetylation of histone H3 by the p300 and CREB-binding protein associated factor, PCAF, suppressed the kinase-dependent inhibition of transcription. These results suggest that acetylation of histones may stimulate transcription by suppressing an inhibitory phosphorylation by a kinase as MSK1. | SIGNOR-262942 |
P12882 | Q02078 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.355 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238748 |
P46527 | Q13315 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.419 | We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks. | SIGNOR-279392 |
P68104 | P51784 | 0 | deubiquitination | up-regulates activity | 0.2 | USP11 interacted with and deubiquitinated eEF1A1 on Lys439, thereby inhibiting its ubiquitin-mediated degradation. Subsequently, the elevated expression of eEF1A1 resulted in its binding to SP1, which in turn drove the binding of SP1 to its target HGF gene promoter to increase its transcription | SIGNOR-278107 |
P04626 | P00519 | 1 | phosphorylation | up-regulates activity | 0.373 | In this study, we show that Abl kinase SH2 domains bind directly to Her-2, and like PDGFR-beta, Her-2 directly phosphorylates c-Abl. | SIGNOR-279407 |
P00742 | P38435 | 0 | carboxylation | up-regulates activity | 0.615 | This report describes the expression, purification, and characterization of a series of recombinant factor Xa variants bearing aspartate substitutions for each of the glutamate residues which normally undergo gamma-carboxylation. |We have produced fully active recombinant human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical for normal activity of factor Xa.|This observation suggests that, for wild-type r-fX expressed in HEK cells, carboxylation by the gamma-glutamyl carboxylase proceeds to completion once initiated; | 11 amino terminal glutamic acid residues of fX which normally undergo gamma-carboxylation (glas 6, 7, 14, 16, 19, 20, 25, 26, 29, 32, 39). | SIGNOR-263667 |
P68400 | Q14676 | 1 | phosphorylation | up-regulates | 0.346 | The mdc1-nbs1 interaction occurs through a specific region (residues 200-420) of mdc1, which contains multiple consensus casein kinase 2 (ck2) phosphorylation sites. | SIGNOR-179887 |
P17612 | Q9Y6Q9 | 1 | phosphorylation | up-regulates | 0.364 | Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites. | SIGNOR-129349 |
P00533 | P0DP25 | 1 | phosphorylation | down-regulates | 0.382 | Phosphorylation of calmodulin by the epidermal-growth-factor-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-266335 |
O14757 | P53350 | 1 | phosphorylation | down-regulates activity | 0.314 | Chk1 directly phosphorylates Plk1 to disturb its interaction with Sgo1. | SIGNOR-277914 |
P12268 | P31749 | 0 | phosphorylation | up-regulates activity | 0.386 | Further, we have demonstrated an in vivo association of IMPDH and PKB/Akt by co‐immunoprecipitation from COS cells expressing a constitutively active form of PKB/Akt. Finally, we were able to show that this constitutively active PKB/Akt could phosphorylate IMPDH in vitro. Thus, the interplay between PKB/Akt and IMPDH reported here could suggest that PKB/Akt activation leads to IMPDH type II activation which in turn prepares the cell for entry into S phase. | SIGNOR-261262 |
Q03060 | P60568 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.481 | In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production. | SIGNOR-261576 |
Q9NY61 | P49137 | 0 | phosphorylation | up-regulates | 0.327 | Upon genotoxic stress, aatf is phosphorylated by the checkpoint kinase mk2. Phosphorylation results in the release of aatf from cytoplasmic mrlc3 and subsequent nuclear translocation where aatf binds to the puma, bax and bak promoter regions to repress p53-driven expression of these pro-apoptotic genes. | SIGNOR-191935 |
P46060 | P06493 | 0 | phosphorylation | up-regulates | 0.495 | Here, we show that rangap1 is phosphorylated on residues t409, s428, and s442. Phosphorylation occurs before nuclear envelope breakdown and is maintained throughout mitosis . Alternatively, phosphorylated rangap1 may recruit specific sumo target proteins to ranbp2's catalytic domain. | SIGNOR-123520 |
Q96PU5 | Q9UI33 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.288 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253462 |
Q9NZ72 | P49840 | 0 | phosphorylation | up-regulates activity | 0.252 | Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta | SIGNOR-264883 |
O15111 | Q15717 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.323 | Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli. | SIGNOR-276422 |
Q16236 | P08263 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.342 | 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-256278 |
P53350 | Q9NS56 | 1 | phosphorylation | up-regulates activity | 0.445 | Plk1-mediated phosphorylation of topors regulates p53 stabilityherein, we have identified topoisomerase i-binding protein (topors), a p53-binding protein, as a plk1 target. We show that plk1 phosphorylates topors on ser(718) in vivo. Significantly, expression of a plk1-unphosphorylatable topors mutant (s718a) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (sumo e3) ligase. Plk1-mediated phosphorylation of topors inhibits topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. | SIGNOR-185838 |
P46937 | Q9NRM7 | 0 | phosphorylation | down-regulates | 0.821 | Lats1/2 inhibit yap by direct phosphorylation at s127, which results in yap binding to 14-3-3 and cytoplasmic sequestration | SIGNOR-198514 |
Q05513 | P27448 | 1 | phosphorylation | down-regulates | 0.2 | Hpar-1a, t564, is phosphorylated in vivo and by apkc in vitro.This study establishes a novel functional link between two central determinants of cellular polarity, apkc and par-1, and suggests a model by which apkc may regulate par-1 in polarized cells | SIGNOR-124221 |
Q9HCK8 | P48431 | 1 | transcriptional regulation | down-regulates quantity | 0.318 | Many of the most significantly up-regulated genes in Chd8+/− and Chd8−/− NPCs are involved in later stages of neuronal development, including Ascl1 [a central driver of neural reprogramming (29)], Dcx, Map2, Nefm, Neurod4, and Neurog1 (Fig. 2 E and F). Additionally, we found that Sox3 is derepressed in both Chd8+/− and Chd8−/− NPCs, and several other Sox TF members (Sox2, Sox7, and Sox11) became derepressed in the Chd8−/− cells | SIGNOR-268921 |
P53350 | Q9Y2Z0 | 1 | phosphorylation | up-regulates activity | 0.437 | Plk1 phosphorylates Sgt1 at the kinetochores to promote timely kinetochore-microtubule attachment|Plk1 is required for the kinetochore localization of Sgt1 and phosphorylates serine 331 of Sgt1 at the kinetochores. This phosphorylation event enhances the association of the Hsp90-Sgt1 chaperone | SIGNOR-265222 |
P07202 | P01266 | 1 | catalytic activity | up-regulates activity | 0.505 | After transport through the apical membrane, I− is covalently bound to the tyrosyl residues of Tg by thyroid peroxidase (TPO). | SIGNOR-259914 |
P04637 | P63241 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.364 | eIF5A regulated p53 protein expression. Further analysis by reverse transcription PCR showed eIF5A-activated p53 transcription. The effect of eIF5A on p53 transcriptional activity was further demonstrated by the increasing expressions of p21 and Bax, well known target genes of p53. | SIGNOR-266375 |
P30307 | P11309 | 0 | phosphorylation | up-regulates activity | 0.348 | First, Pim-1 activates the Cdc25C phosphatase directly through phosphorylation, very probably at the N-terminal part of the protein.|We find that phosphorylation by Pim-1 enhances the phosphatase activity of Cdc25C and in transfected cells that are arrested in G2/M by bleomycin, Pim-1 can enhance progression into G1. | SIGNOR-278298 |
Q9ULT6 | Q14332 | 1 | ubiquitination | down-regulates | 0.292 | Znrf3 is associated with the wnt receptor complex, and inhibits wntby promoting the turnover of frizzled and lrp6. | SIGNOR-197417 |
P00734 | P01008 | 0 | cleavage | down-regulates activity | 0.948 | Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 | SIGNOR-264136 |
Q15831 | P27448 | 1 | phosphorylation | up-regulates activity | 0.315 | Regulation of the wnt signalling component par1a by the peutz-jeghers syndrome kinase lkb1. Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1. Mark3 is activated by phosphorylation on thr-211. | SIGNOR-104059 |
P09237 | P10915 | 1 | cleavage | down-regulates quantity by destabilization | 0.322 | Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix. | SIGNOR-256329 |
Q13131 | Q15831 | 0 | phosphorylation | up-regulates activity | 0.599 | The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. | SIGNOR-139297 |
Q02078 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.506 | Cdk5-mediated inhibition of the protective effects of transcription factor mef2 in neurotoxicity-induced apoptosis.We have identified the prosurvival transcription factor mef2 as a direct nuclear target of cdk5. Cdk5 phosphorylates mef2 at a distinct serine in its transactivation domain to inhibit mef2 activity. | SIGNOR-100574 |
P42681 | P12931 | 0 | phosphorylation | up-regulates activity | 0.348 | We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association. | SIGNOR-247346 |
Q13547 | P68400 | 0 | phosphorylation | up-regulates | 0.62 | Human hdac1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, ser(421) and ser(423), were unambiguously identified. Loss of phosphorylation at ser(421) and ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of hdac1. | SIGNOR-111015 |
Q13131 | P52292 | 1 | phosphorylation | up-regulates | 0.2 | Ampk phosphorylated importin alpha1 on ser(105). Accordingly, expression of importin alpha1 proteins bearing k22r or s105a mutations failed to mediate the nuclear import of hur in intact cells. Our results point to importin alpha1 as a critical downstream target of ampk and key mediator of ampk-triggered hur nuclear import. | SIGNOR-128629 |
P08069 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.861 | Ptp-1b can regulate igf-ir kinase activity and function and that loss of ptp-1b can enhance igf-i-mediated cell survival, growth, and motility in transformed cells. | SIGNOR-115709 |
P04637 | Q9NYY3 | 0 | phosphorylation | up-regulates activity | 0.592 | Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. | SIGNOR-278980 |
O75444 | P49841 | 0 | phosphorylation | down-regulates | 0.26 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159438 |
P56524 | Q16566 | 0 | phosphorylation | down-regulates activity | 0.62 | CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus. | SIGNOR-250712 |
Q8WYQ5 | Q13315 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.27 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277307 |
Q13627 | Q12879 | 1 | phosphorylation | up-regulates quantity | 0.397 | DYRK1A enhances the surface expression of GluN1 and GluN2A receptors.|Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser 1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. | SIGNOR-279327 |
P11802 | Q08050 | 1 | phosphorylation | up-regulates | 0.624 | We identified the forkhead box m1 (foxm1) transcription factor as a common critical phosphorylation target. Cdk4/6 stabilize and activate foxm1, thereby maintain expression of g1/s phase genes, suppress the levels of reactive oxygen species (ros), and protect cancer cells from senescence. | SIGNOR-177266 |
P18846 | P18146 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.275 | Phosphorylated CREB and ATF1 then bind to the CRE of the egr-1 promoter and cause a stress-dependent transcriptional activation of this gene. | SIGNOR-271686 |
O43353 | O14733 | 1 | phosphorylation | up-regulates activity | 0.44 | Collectively, the results suggest that RIPK2 binds to and activates MKK7.|Radioactive in vitro kinase assay showed that RIPK2 can directly phosphorylate kinase-dead (K149A) MKK7 (Fig.\u00a0 xref ). | SIGNOR-280105 |
P32314 | P51812 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Importantly, we identified RSK2 kinase as the upstream kinase for the FOXN2 phosphodegron. The Ser365 and Ser369 sites in a conserved DSGYAS motif are responsible for the ubiquitination of FOXN2 by β-Trcp. | SIGNOR-273841 |
Q96GD4 | O14777 | 1 | phosphorylation | down-regulates | 0.848 | To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant). | SIGNOR-165558 |
P03372 | P24941 | 0 | phosphorylation | up-regulates | 0.477 | The pi3k/akt pathway is necessary to activate cdk2, which phosphorylates eralphaser294, and mediates the binding between pin1 and eralpha | SIGNOR-200867 |
P12931 | O14965 | 1 | phosphorylation | up-regulates activity | 0.309 | We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement. | SIGNOR-279286 |
Q05513 | Q7KZI7 | 1 | phosphorylation | down-regulates | 0.266 | Hpar-1b is phosphorylated by apkc on threonine 595 importantly, phosphorylation of hpar-1b on t595 negatively regulates the kinase activity and plasma membrane localization of hpar-1b in vivo. | SIGNOR-124217 |
O95863 | Q05513 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | APKC kinases phosphorylate S249 of SNAI1, which leads to protein degradation. | SIGNOR-277437 |
Q9H4B4 | P30304 | 1 | phosphorylation | down-regulates | 0.383 | Here, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cdc25a to promote its proteolysis in early cell-cycle phases. Phosphorylation by gsk-3beta requires priming of cdc25a, and this can be catalyzed by polo-like kinase 3 (plk-3) | SIGNOR-160228 |
O43524 | Q06418 | 0 | phosphorylation | down-regulates activity | 0.2 | However, the present study in tPA and NMDA treated neurons establishes the link between PS mediated activation of Tyro3 and FKHRL1 phosphorylation which inactivates pro apoptotic FKHRL1 and mediates PS 's beneficial effects.|We also show that inhibition of the extrinsic apoptotic cascade by PS requires Tyro3 mediated phosphorylation of FKHRL1 which in turn inhibits FasL production and FasL dependent caspase-8 activation in the extrinsic pathway. | SIGNOR-279669 |
O43474 | Q9Y4K3 | 0 | ubiquitination | up-regulates quantity by stabilization | 0.285 | We further found that inhibition of polo-like kinase 1 could downregulate the expression of KLF4 and that PLK1 directly phosphorylated KLF4 at Ser234. Notably, phosphorylation of KLF4 by PLK1 caused the recruitment and binding of the E3 ligase TRAF6, which resulted in KLF4 K32 K63-linked ubiquitination and stabilization. | SIGNOR-277464 |
P46937 | P49674 | 0 | phosphorylation | down-regulates | 0.422 | Phosphorylation of YAP (S381) and TAZ (S311) by Lats1/2 primes subsequent phosphorylation events by Casein Kinase 1 (CK1d/e); this sequential phosphorylation results in recruitment of b-transducin repeat-containing proteins (b-TRCP; a subunit of the SCF ubiquitin E3 ligase) and consequently leads to degradation of YAP/TAZ | SIGNOR-201170 |
Q07343-2 | P28482 | 0 | phosphorylation | up-regulates activity | 0.268 | The short-form PDE4B2 isoenzyme was activated by Erk2 phosphorylation. These functional changes in PDE activity were mimicked by mutation of the target serine for Erk2 phosphorylation to the negatively charged amino acid, aspartic acid. | SIGNOR-275971 |
Q92934 | P41743 | 0 | phosphorylation | down-regulates | 0.32 | In-vitro kinase activity assay showed that pkc-_ directly phosphorylated bad at phospho specific residues, ser-112, ser-136 and ser-155 which in turn induced inactivation of bad and disruption of bad/bcl-xl dimer | SIGNOR-172894 |
P17661 | Q14814 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Ectopic expression of myogenin and a specific Mef2 isoform induced myogenic differentiation without activating endogenous MyoD expression. Under these conditions, the regulatory sequences of late gene loci were not in close proximity, and these genes were prematurely activated. | SIGNOR-241504 |
O60346 | P31751 | 1 | dephosphorylation | down-regulates activity | 0.621 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248328 |
Q9UPZ9 | Q8N122 | 1 | phosphorylation | up-regulates | 0.2 | Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division. | SIGNOR-196198 |
P30411 | P34947 | 0 | phosphorylation | down-regulates activity | 0.489 | Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration. | SIGNOR-251208 |
O94782 | Q8WYQ5 | 1 | deubiquitination | up-regulates quantity by stabilization | 0.2 | Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. | SIGNOR-277308 |
P17252 | Q05209 | 1 | phosphorylation | down-regulates | 0.322 | Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate. | SIGNOR-27300 |
P06493 | O00562 | 1 | phosphorylation | up-regulates | 0.465 | T287 is phosphorylated by cdk1 during mitosis. Phosphorylation of nir2 by cdk1 facilitates its dissociation from the golgi apparatus, and phospho-nir2(ps382) is localized in the cleavage furrow and midbody during cytokinesis. | SIGNOR-124642 |
P42345 | Q96F24 | 1 | phosphorylation | up-regulates activity | 0.2 | Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association. | SIGNOR-265875 |
P12814 | P18031 | 0 | dephosphorylation | up-regulates | 0.335 | Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase. | SIGNOR-141634 |
Q9Y2N7 | Q9BXM7 | 0 | phosphorylation | down-regulates activity | 0.347 | Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. | SIGNOR-263090 |
O15111 | Q9C0C7 | 1 | phosphorylation | up-regulates activity | 0.2 | Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. | SIGNOR-272974 |
O75582 | P18846 | 1 | phosphorylation | up-regulates activity | 0.69 | Using embryonic fibroblasts derived from these mice we were able to demonstrate an important role for these enzymes in the activation of CREB and the closely related transcription factor ATF1. | Our results clearly demonstrate that MSK1 and MSK2 are the major, if not the only, protein kinases that mediate the phosphorylation of CREB at Ser133 and of ATF1 at Ser63 in fibroblasts | SIGNOR-249144 |
P78536 | P27361 | 0 | phosphorylation | up-regulates | 0.361 | Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated sheddingwe show that extracellular signal-regulated kinase (erk) acts as an intermediate in protein kinase c-regulated trka cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (tace) is phosphorylated by erk at threonine 735. In addition, we show that erk and tace associate. This association is favored by erk activation and by the presence of threonine 735. In contrast to the erk route, the p38 mapk was able to stimulate trka cleavage in cells devoid of tace activity, indicating that other proteases are also involved in trka shedding. | SIGNOR-89625 |
Q9HC98 | O95235 | 1 | phosphorylation | down-regulates activity | 0.347 | We show that Nek9, Nek6, and the kinesin Mklp2 form a signaling module, which is required for Mklp2 to localize to the central spindle in anaphase. Nek6 also phosphorylates Mklp2 at Ser244, inhibiting its bundling activity until anaphase onset. | SIGNOR-273891 |
O14965 | Q96EZ8 | 1 | phosphorylation | up-regulates activity | 0.316 | We conclude that Aurora-A phosphorylates MCRS1 on Ser35/36 specifically during mitosis. | SIGNOR-278232 |
P0CG48 | P45974 | 0 | cleavage | up-regulates quantity | 0.847 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270822 |
Q92934 | Q13153 | 0 | 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 |
P84022 | O14595 | 0 | dephosphorylation | up-regulates activity | 0.424 | Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248293 |
P0DMV8 | P22413 | 1 | post transcriptional regulation | up-regulates quantity | 0.2 | We demonstrated the binding of heat shock protein 70 (HSP70) to ENPP1-3'UTR. Through this binding, HSP70 stabilizes ENPP1 mRNA and increases ENPP1 transcript and protein levels. This positive modulation of ENPP1 expression is paralleled by a reduced insulin-induced IR and IRS-1 phosphorylation. | SIGNOR-252197 |
Q14500 | P17612 | 0 | phosphorylation | down-regulates activity | 0.283 | Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚ | SIGNOR-249998 |
Q6SZW1 | P45983 | 0 | phosphorylation | down-regulates activity | 0.423 | C-Jun N-terminal kinase (JNK)-mediated phosphorylation of SARM1 regulates NAD+ cleavage activity to inhibit mitochondrial respiration|Here, we report that NAD+ cleavage activity of SARM1 is regulated by its own phosphorylation at serine 548. The phosphorylation of SARM1 was mediated by c-jun N-terminal kinase (JNK) under oxidative stress conditions, resulting in inhibition of mitochondrial respiration concomitant with enhanced activity of NAD+ cleavage. Nonphosphorylatable mutation of Ser-548 or treatment with a JNK inhibitor decreased SARM1 activity. | SIGNOR-275554 |
P17947 | P49715 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.528 | Activation of C/EBPα induces PU.1 expression, cell cycle arrest, and differentiation in 32D cells expressing FLT3/ITD | SIGNOR-261531 |
Q13131 | Q9NP71 | 1 | phosphorylation | down-regulates | 0.451 | Ampk has also been suggested to phosphorylate the glucose-sensitive transcription factor chrebpthe dna binding activity, as assayed in a gel-shift assay of the truncated chrebp, was gradually inactivated with time by treatment with ampk | SIGNOR-176494 |
Q9NRY4 | P61586 | 1 | gtpase-activating protein | down-regulates activity | 0.893 | 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-260492 |
P62714 | O14920 | 1 | dephosphorylation | down-regulates activity | 0.259 | Permanent activation of the upstream kinase IKK beta results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized I kappaB alpha|Chronic Ser 177/181 phosphorylation of IKKβ was due to UVB-induced inhibition of the catalytic subunit of the Ser-Thr phosphatase PP2A (PP2Ac) | SIGNOR-248580 |
Q9Y4G8 | P62834 | 1 | guanine nucleotide exchange factor | up-regulates activity | 0.789 | Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity.Increased intracellular concentrations of cAMP enhanced the Rapgef2-dependent activation of Rap1, which in turn associated with B-Raf to enable the activation of ERK and subsequent neuronal- and endocrine-specific cellular outcomes, such as induction of neuroendocrine-specific genes and extension of neuritic processes (neuritogenesis). | SIGNOR-276609 |
P23470 | P42224 | 1 | dephosphorylation | up-regulates activity | 0.2 | 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-254727 |
P48751 | Q02156 | 0 | phosphorylation | up-regulates activity | 0.309 | We conclude that following Ang II stimulation of cells, PKCepsilon phosphorylates serine 67 of the AE3 cytoplasmic domain, inducing the Ang II-induced increase in anion transport observed in the hypertrophic myocardium. | SIGNOR-249127 |
Q9H190 | P30408 | 0 | relocalization | up-regulates activity | 0.402 | TM4SF1 functions as a membrane adaptor connecting DDR1 to syntenin2. | SIGNOR-272401 |
Q99661 | O14965 | 0 | phosphorylation | down-regulates activity | 0.584 | In addition, we found that MCAK localization at spindle poles was regulated through another Aurora A phosphorylation site (S719), which positively enhances bipolar spindle formation. | SIGNOR-279139 |
P45983 | P17275 | 1 | phosphorylation | up-regulates activity | 0.719 | JunB-control of IL-4 expression is mediated by the phosphorylation of JunB at Thr102 and -104 by JNK MAP kinase. The synergy between c-Maf and JunB can be attributed to cooperative DNA binding, which is facilitated by JunB phosphorylation. | SIGNOR-250120 |
P78317 | Q9UGL1 | 1 | sumoylation | down-regulates quantity by destabilization | 0.3 | Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015). | SIGNOR-271575 |
O14920 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.517 | Activation of IkappaB kinase beta by protein kinase C isoforms. | Interestingly, recombinant active zetaPKC and alphaPKC are able to stimulate in vitro the activity of IKKbeta but not that of IKKalpha. In addition, evidence is presented here that recombinant zetaPKC directly phosphorylates IKKbeta in vitro, involving Ser177 and Ser181. Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation. | SIGNOR-249015 |
O60315 | O00257 | 0 | sumoylation | down-regulates quantity by destabilization | 0.331 | Pc2 can act directly as an E3 ligase for SIP1 sumoylation.SIP1 sumoylation having a negative effect on its repression of E-cadherin transcription. | SIGNOR-268955 |
Q00535 | Q9Y696 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | These results confirm that CDK5 phosphorylates CLIC4 at serine 108.|We found that activated CDK5 phosphorylated serine 108 in CLIC4, increasing CLIC4 protein stability, and accumulation. | SIGNOR-279451 |
P06239 | P20963 | 1 | phosphorylation | up-regulates | 0.764 | During tcr signaling, lck interacts with numerous molecules, including tcr-zeta. The binding of lck to the tyrosine-phosphorylated zeta chain of the tcr would serve to strengthen the interaction of the associated cd4 and the tcr complex, leading to increased avidity for the antigen-major histocompatibility protein complex. | SIGNOR-41361 |
P14618 | P29350 | 0 | dephosphorylation | down-regulates activity | 0.2 | SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs.|SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated hepatocellular carcinoma cells.|SHP-1 dephosphorylates p-PKM2Y105 and further affects the nucleus-related cell proliferation. | SIGNOR-276997 |
Q12778 | O00141 | 0 | phosphorylation | down-regulates activity | 0.607 | We demonstrate that SGK1 affects differentiation by direct phosphorylation of Foxo1, thereby changing its cellular localization from the nucleus to the cytosol. In addition we show that SGK1-/- cells are unable to relocalize Foxo1 to the cytosol in response to dexamethasone. | SIGNOR-255925 |
P29322 | Q12857 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8) | SIGNOR-268896 |
P01106 | P28482 | 0 | phosphorylation | up-regulates activity | 0.735 | Transactivation of gene expression by myc is inhibited by mutation at the phosphorylation sites thr-58 and ser-62. | SIGNOR-235700 |
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