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 |
|---|---|---|---|---|---|---|---|
Q05397 | P43146 | 0 | binding | up-regulates activity | 0.72 | Here we show that different regions of the intracellular domain of DCC directly interacted with the tyrosine kinases Src and focal adhesion kinase (FAK). Netrin activated both FAK and Src and stimulated tyrosine phosphorylation of DCC. Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin. Mutation of the tyrosine phosphorylation residue in DCC abolished its function of mediating netrin-induced axon attraction. On the basis of our observations, we suggest a model in which DCC functions as a kinase-coupled receptor, and FAK and Src act immediately downstream of DCC in netrin signaling. | SIGNOR-268371 |
P01106 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.72 | Phosphorylation of Thr 58, likely mediated by GSK-3 but dependent on the prior phosphorylation of Ser 62, is associated with degradation of Myc. | SIGNOR-252080 |
P10916 | Q15746 | 0 | phosphorylation | up-regulates activity | 0.72 | MLCK directly phosphorylates MLC2 and is a substrate for ERK1/2 ( ), thus providing a direct link between the Raf-MEK1/2-ERK1/2 module and MLC2.|These findings strongly suggest that the phosphorylation of MLC2 stimulated by MLCK and ROCK1/2 is an integral component of the biochemical signal transduction program that promotes noninvasive motility. | SIGNOR-279233 |
Q13163 | Q99759 | 0 | phosphorylation | up-regulates | 0.72 | Mekk2 and mekk3 are mapk kinase kinases that bind, phosphorylate and activate mek5. | SIGNOR-104637 |
P42224 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.72 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154779 |
P25106 | P48061 | 0 | binding | up-regulates | 0.72 | Here we show that cxcl12, the only known natural ligand for cxcr4, binds to and signals through rdc1. | SIGNOR-139709 |
P35222 | P16591 | 0 | phosphorylation | down-regulates activity | 0.72 | Interaction of beta-catenin with alpha-catenin is regulated by the phosphorylation of beta-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. | SIGNOR-251131 |
Q13077 | P20333 | 0 | binding | up-regulates | 0.72 | Traf1 interacts with tnf-r2 indirectly through heterodimer formation with traf2. | SIGNOR-33133 |
P12931 | P17706 | 0 | dephosphorylation | down-regulates | 0.72 | We found that tcptp dephosphorylates and inactivates src family kinases to regulate t cell responses._ | SIGNOR-177116 |
P10275 | Q02790 | 0 | binding | up-regulates activity | 0.72 | We noted that FK506 altered nuclear localization of the GR and inhibited expression of GR-responsive genes. Furthermore, si-RNA knockdown of FKBP4 gene, coding for the immunophilin FKBP52, inhibited cortisol-activated GR nuclear translocation | SIGNOR-252034 |
P14649 | Q15746 | 0 | phosphorylation | up-regulates | 0.72 | Cytoskeletal dynamics are primarily modulated by interactions of actin and myosin ii that are regulated by myosin light chain kinase (mlck)-mediated phosphorylation of the regulatory myosin light chain (mlc). | SIGNOR-65865 |
P56705 | Q8N474 | 0 | binding | down-regulates | 0.72 | Sfrp-1 binds wnt-4 with considerable avidity and inhibits the dna-binding activity of tcf, an effector of wnt signaling, | SIGNOR-106556 |
Q14204 | Q9GZM8 | 0 | binding | up-regulates activity | 0.72 | LIS1 specifically binds the P1 loop domain of CDHC, while NUDEL binds the C-terminal region as well as a distinct binding site in the P1 loop domain. LIS1 and NUDEL regulate CDHC localization and motor function. Reduction of LIS1 leads to mislocalization of NUDEL, CDHC, β-tubulin, and the Golgi complex | SIGNOR-252159 |
P04637 | Q96GD4 | 0 | phosphorylation | down-regulates | 0.719 | We show that aurora b phosphorylates p53 at s183, t211, and s215 to accelerate the degradation of p53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of p53 target genes involved in cell cycle inhibition and apoptosis (e.g., p21 and puma). | SIGNOR-197598 |
P63000 | Q8TCU6 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.719 | 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-260569 |
P17275 | P45983 | 0 | 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 |
Q6UXL0 | Q9UHD0 | 0 | binding | up-regulates | 0.719 | Il-19 signals only through the type i il-20r complex. | SIGNOR-151820 |
P05107 | Q9Y490 | 0 | binding | up-regulates activity | 0.719 | Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails. | SIGNOR-257618 |
P01308 | P14735 | 0 | cleavage | down-regulates quantity by destabilization | 0.719 | IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds | SIGNOR-260986 |
P09874 | P55210 | 0 | cleavage | down-regulates | 0.719 | Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis. | SIGNOR-83703 |
P56645 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.719 | We show here that mPer proteins, negative limbs of the autoregulatory loop, are specific substrates for CKIepsilon and CKIdelta. The CKI phosphorylation of mPer1 and mPer3 proteins results in their rapid degradation, which is dependent on the ubiquitin-proteasome pathway. | SIGNOR-267998 |
Q15349 | P27361 | 0 | phosphorylation | up-regulates | 0.719 | Several lines of investigation have suggested that rsk is phosphorylated and activated by erk1/2 mapk isoforms | SIGNOR-44949 |
Q8IXI1 | Q9BXM7 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.719 | PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. in Miro1, Ser156 (homologous to Ser182 in Drosophila) and Thr298, 299 (homologous to Ser324, 325 in Drosophila, Figure 6C). | SIGNOR-272727 |
P05412 | Q04206 | 0 | binding | up-regulates | 0.719 | Chromatin immunoprecipitation (chip) analysis confirmed the serum-induced recruitment of jund to the promoter in vivo and showed that the presence of jund was dependent on the presence of p65 and p50, indicating a protein-protein-dependent mechanism of jund recruitment | SIGNOR-160330 |
P84077 | Q92538 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.719 | GBF1 Stimulates Production of Arf-GTP In Vivo | SIGNOR-277400 |
P27986 | P08069 | 0 | binding | up-regulates | 0.718 | Igf-1 activated both the pi3k and the extracellular signal-regulated kinase [?] (erk [?]) Pathways as evidenced by phosphorylation of either akt or erk1 [?]/2 (respectively) | SIGNOR-179386 |
P10244 | P24941 | 0 | phosphorylation | up-regulates activity | 0.718 | Ten phosphorylation sites carboxyl-terminal to the DNA-binding domain were identified by this method: threonines at positions 267, 408, 497, 519, 522, and 524 and serines at positions 283, 396, 455, and 581. | Our results indicate that B-Myb can be phosphorylated in a cell-free system by both cyclin A-Cdk2 and cyclin E-Cdk2 complexes. | These data suggest that B-Myb is a target for phosphorylation by cyclin-Cdk2 and that phosphorylation of B-Myb regulates its transcriptional activity. | SIGNOR-250735 |
Q15418 | P27361 | 0 | phosphorylation | up-regulates activity | 0.718 | Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity.Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-102648 |
Q9BRV8 | Q9UHD2 | 0 | phosphorylation | down-regulates quantity | 0.718 | Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity. | SIGNOR-280152 |
P06858 | Q6Q788 | 0 | binding | up-regulates activity | 0.718 | Apo A5 binds to and enhances the activity of lipoprotein lipase (LPL) enzyme | SIGNOR-251845 |
Q08379 | P62820 | 0 | relocalization | up-regulates activity | 0.718 | Here, we demonstrate that the cis ‐Golgi tethering protein GM130, complexed with GRASP65 and other proteins, forms a novel Rab1 effector complex that interacts with activated Rab1‐GTP in a p115‐independent manner and is required for coat protein II vesicle targeting/fusion with the cis ‐Golgi | SIGNOR-261285 |
Q13233 | Q12933 | 0 | binding | up-regulates | 0.718 | Traf2, ubc13, and ikkgamma were required for complex assembly and activation of mekk1 and mapk cascades. | SIGNOR-179476 |
P61224 | O95398 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.718 | Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well. | SIGNOR-263957 |
P16234 | P01127 | 0 | binding | up-regulates activity | 0.718 | Pdgf-b activates both pdgfr-alpha and pdgfr-beta | SIGNOR-107397 |
P01100 | P14921 | 0 | transcriptional regulation | up-regulates quantity | 0.718 | Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control. | SIGNOR-256495 |
Q04206 | O75582 | 0 | phosphorylation | up-regulates | 0.718 | Transcriptional activation of the nf-kappab p65 subunit by mitogen- and stress-activated protein kinase-1 (msk1)mutational analysis of p65 revealed ser276 as a target for phosphorylation and transactivation in response to tnf. Moreover, we identified msk1 as a nuclear kinase for p65, since msk1 associates with p65 in a stimulus-dependent way and phosphorylates p65 at ser276. | SIGNOR-99210 |
P60953 | Q96N96 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.718 | 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-260576 |
P46937 | P00519 | 0 | phosphorylation | up-regulates | 0.718 | In this study, we show that c-abl directly phosphorylates yap1 at position y357 in response to dna damage. Tyrosine-phosphorylated yap1 is a more stable protein that displays higher affinity to p73 and selectively coactivates p73 proapoptotic target genes. | SIGNOR-160860 |
O43524 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.717 | Here, we show that erk downregulates forkhead box o 3a (foxo3a) by directly interacting with and phosphorylating foxo3a at ser 294, ser 344 and ser 425, which consequently promotes cell proliferation and tumorigenesisMDM2 is required for ERk-mediated FOXO3a degradation. | SIGNOR-160415 |
P01100 | P27361 | 0 | phosphorylation | up-regulates activity | 0.717 | In a previous study we have observed that exposure of nih 3t3 cells to pdgf or serum leads to c-fos phosphorylation by erk on specific residues, thr232, thr325, thr331, and ser374, within the cooh-terminal c-fos tad we have recently shown that erk phosphorylates multiple residues within the carboxylterminal transactivation domain (tad) of c-fos, thus resulting in its increased transcriptional activity. | SIGNOR-118023 |
P23528 | Q8TE77 | 0 | dephosphorylation | up-regulates activity | 0.717 | Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH). | SIGNOR-248759 |
Q12770 | Q9Y5U4 | 0 | binding | down-regulates activity | 0.717 | insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. | SIGNOR-256209 |
P0CG48 | Q96BN8 | 0 | cleavage | up-regulates quantity | 0.717 | 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-270820 |
Q15349 | P28482 | 0 | phosphorylation | up-regulates | 0.717 | Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3. | SIGNOR-161515 |
Q14790 | P27361 | 0 | phosphorylation | down-regulates | 0.717 | We demonstrate that perk 1/2 can phosphorylate pro-caspase-8 at s387 by knocking-down the endogenous pro-caspase-8 using rnai and replacing it with its non-phosphorylatable counterpart (s387a), a significant increase in caspase-8 activity | SIGNOR-203480 |
Q9HB96 | O14757 | 0 | phosphorylation | up-regulates | 0.716 | Chk1 directly phosphorylates the fance subunit of the fa core complex on two conserved sites (threonine 346 and serine 374). chk1-mediated phosphorylation of fance is required for the fanconi anemia/brca pathway. | SIGNOR-153023 |
P13693 | P53350 | 0 | phosphorylation | down-regulates | 0.716 | Plk phosphorylates tctp on two serine residues. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of tctp and promotes the increase in microtubule dynamics that occurs after metaphase | SIGNOR-91348 |
O60341 | Q96BD5 | 0 | binding | down-regulates activity | 0.716 | BHC80 Inhibits LSD1 Demethylase Activity In Vitro. in contrast to CoREST, which is a positive regulator of LSD1 activity, the in vitro evidence presented above suggests that BHC80 may function to inhibit LSD1 activity. | SIGNOR-264505 |
P62714 | Q9Y570 | 0 | demethylation | down-regulates activity | 0.716 | Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans. | SIGNOR-265750 |
P49407 | P27361 | 0 | phosphorylation | down-regulates | 0.716 | Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation | SIGNOR-67634 |
O43521 | P28482 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.716 | In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel | SIGNOR-129874 |
P23458 | P24394 | 0 | binding | up-regulates | 0.716 | IL-4Rα, γc, and IL-13Rα1 all contain proline-rich box-1 regions that bind jak1, jak3, and tyk2, respectively. Il-4 uses the type ii receptor, and IL-13R1 Binds tyk2. Il-13 results in activation of jak1 and tyk2 in hematopoietic and nonhematopoietic cells. | SIGNOR-100774 |
P17676 | P28482 | 0 | phosphorylation | up-regulates | 0.716 | Phosphorylation of cebpb at thr(235) peaked at 16 hours in il-1beta-stimulated cells. The mek inhibitor u0126 inhibited this phosphorylation and reduced mmp-1 gene induction. | SIGNOR-187798 |
Q00987 | P00519 | 0 | phosphorylation | down-regulates activity | 0.716 | C-abl binds and phosphorylates mdm2 in vivo and in vitro;phosphorylation of mdm2 by c-abl impairs the inhibition of p53 by mdm2. | SIGNOR-90512 |
P60953 | P98174 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.716 | 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-260551 |
O15350 | P46937 | 0 | binding | up-regulates | 0.716 | Yap also interacts with p73, a p53 family pro-apoptotic transcription factor, to induce expression of genes such as bax, puma and pml. | SIGNOR-175934 |
Q9BQQ3 | P06493 | 0 | phosphorylation | down-regulates activity | 0.715 | Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events. | SIGNOR-262840 |
Q8TDX7 | Q8TD19 | 0 | phosphorylation | up-regulates activity | 0.715 | Nercc1 catalyzes the phosphorylation of nek6 (ser206) and the equivalent site on nek7 (ser195), resulting in a 20-25-fold activation of nek6/7 kinase activity | SIGNOR-103030 |
P63000 | P46940 | 0 | binding | down-regulates activity | 0.715 | Although the name implies that it functions as a GTPase-activating protein, IQGAP1 actually stabilizes Cdc42 and Rac1 in the active, GTP-bound form (5, 8, 17). Thus, IQGAP1 acts as an “anti-GTPase-activating protein” for Cdc42 and Rac1, with marked effects on the cytoskeleton. | SIGNOR-261889 |
P07949 | Q99748 | 0 | binding | up-regulates | 0.715 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49122 |
Q09428 | Q8WZA2 | 0 | binding | up-regulates quantity | 0.715 | The SUR1 subunit of KATP channels recruits Epac2 to the plasma membrane where a signaling complex comprised of Epac2, Rap1 and PLC-ε is formed. Rap1 is activated by Epac2, and the activated form of Rap1 binds to and activates PLC-ε. | SIGNOR-278141 |
Q6R327 | P23443 | 0 | phosphorylation | down-regulates | 0.715 | Phosphorylation of rictor on thr1135 did not affect mtorc2 assembly, kinase activity, or cellular localization. However, cells expressing a rictor t1135a mutant were found to have increased mtorc2-dependent phosphorylation of akt | SIGNOR-161995 |
P42338 | P01116 | 0 | binding | up-regulates | 0.714 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k. | SIGNOR-175207 |
Q07889 | P28482 | 0 | phosphorylation | down-regulates activity | 0.714 | In this report, we describe the identification of five map kinase sites (s-1137, s-1167, s-1178, s-1193, and s-1197) on hsos1Replacing the MAP kinase phosphorylation sites with alanine residues results in an increase in the binding affinity of Grb2 to hSos1 | SIGNOR-235929 |
P45983 | Q13115 | 0 | dephosphorylation | down-regulates | 0.714 | Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2 | SIGNOR-27756 |
Q16644 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.714 | These results, taken together, suggest the importance of the docking interaction in the efficient phosphorylation and activation of 3pk by p38. | SIGNOR-235451 |
Q04771 | Q13873 | 0 | binding | up-regulates | 0.714 | Bmpr-ii is a transmembrane serine/threonine kinase that binds bmp-2 and bmp-7 in association with multiple type i receptors, including bmpr-ia/brk1, bmpr-ib, and actr-i, which is also an activin type i receptor. | SIGNOR-33434 |
P40189 | P20809 | 0 | binding | up-regulates | 0.714 | Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-4 | SIGNOR-48033 |
Q08334 | P22301 | 0 | binding | up-regulates | 0.714 | The il-10r2 chain is ubiquitously expressed, whereas the il-10 activity is restricted mainly to cells of hematopoietic origin (35, 36). This raised the question of why the second chain of the il-10 receptor complex is widely expressed when its function was required only in limited cellular subsets. One hypothesis is that the il-10r2 chain is shared by receptors for ligands other than il-10 | SIGNOR-83191 |
Q92834 | Q96KN7 | 0 | binding | down-regulates activity | 0.714 | The RPGR H98Q and F130C mutants exhibit compromised interaction with RPGRIP1, suggesting that RPGR–RPGRIP1 interaction may be an important determinant of RPGR activity. As RPGRIP1 appears to link RPGR to the cilium, it is possible that RPGR's effect on RAB8A function may occur in distinct subcellular compartments of photoreceptors and that RPGRIP1 and other interacting proteins may modulate targeting of RPGR to such compartments. | SIGNOR-253031 |
Q13393 | P17252 | 0 | phosphorylation | up-regulates | 0.714 | Serine 2, threonine 147, and serine 561 were identified as phosphorylation sites of pld1 by pkcalpha in the cells. | SIGNOR-69938 |
Q8N5C8 | Q9Y4K3 | 0 | binding | up-regulates activity | 0.714 | The irak1/traf6 complex can also activate jnk and p38 signalling through assembly of a catalytically active tab2-tab3-tak1 complex. | SIGNOR-205461 |
P62330 | Q9Y2X7 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.714 | Activated RAC1 interacts with GIT1, a GAP protein of ARF6, and causes the inactivation of ARF6 [78]. As ARF6 plays a role in the promotion of the recycling of macropinosomes to the plasma membrane, the inactivation of ARF6 by RAC1 reduces the recycling of macropinosomes. | SIGNOR-277784 |
P14317 | P07948 | 0 | phosphorylation | up-regulates activity | 0.714 | Lyn and Syk synergistically phosphorylate HS1, and that Tyr-378 and Tyr-397 of HS1 are the critical residues for its BCR-induced phosphorylation. tyrosine phosphorylation of HS1 is required for BCR-induced apoptosis and nuclear translocation of HS1 may be a prerequisite for B cell apoptosis. PMID: 9104825 PMCID: PMC2196252 | SIGNOR-251401 |
P13807 | Q86XI6 | 0 | binding | up-regulates | 0.714 | In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2) | SIGNOR-271734 |
O14920 | Q99558 | 0 | phosphorylation | up-regulates | 0.714 | Activation of the transcription factor nf-kappab by inflammatory cytokines involves the successive action of nf-kappab-inducing kinase (nik) and two ikappab kinases, ikk-alpha and ikk-beta. Here we show that nik preferentially phosphorylates ikk-alpha over ikk-beta | SIGNOR-55949 |
P10242 | Q9UBE8 | 0 | phosphorylation | down-regulates activity | 0.714 | Furthermore, the downregulation of c-Myb by NLK overexpression could be inhibited in cells that had been treated with the 26S proteasome inhibitor MG132 but not in those treated with DMSO ( ).|HIPK2 and NLK directly bind to c-Myb, and NLK phosphorylates c-Myb at multiple sites, resulting in its ubiquitination and proteasome-dependent degradation [32]. | SIGNOR-280049 |
P24941 | Q16667 | 0 | dephosphorylation | down-regulates activity | 0.714 | The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. | SIGNOR-248724 |
O94855 | Q9NR31 | 0 | binding | up-regulates quantity | 0.714 | Biogenesis of COPII vesicles is initiated by the activation of the small guanosine triphosphate (GTP)-binding protein secretion-associated Ras-related protein 1 (Sar1) at specialized subdomains of the ER, called ER exit sites (ERES) or transitional ER (tER). Membrane-bound Sar1 then recruits the inner COPII coat subcomplex, the Sec23/24 heterodimer. | SIGNOR-265301 |
Q8NEB9 | O75385 | 0 | phosphorylation | up-regulates activity | 0.713 | In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex. | SIGNOR-279670 |
Q13257 | P33981 | 0 | phosphorylation | up-regulates activity | 0.713 | Mps1 is an upstream component of the spindle assembly checkpoint, which, in human cells, is required for checkpoint activation in response to spindle damage but not apparently during an unperturbed mitosis. Mps1 also recruits Mad1 and Mad2 to kinetochores.|Thus, in human cells, Mps1 catalytic activity is required for spindle checkpoint function and recruitment of Mad2. | SIGNOR-252036 |
P12956 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.713 | Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks. | SIGNOR-274020 |
Q04206 | P19838 | 0 | binding | up-regulates activity | 0.713 | Here we report the crystal structure at 2.9 a resolution of the p50/p65 heterodimer bound to the kappab dna | SIGNOR-55378 |
P01116 | Q07890 | 0 | guanine nucleotide exchange factor | up-regulates | 0.713 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85. | SIGNOR-175265 |
Q9NWZ3 | Q9Y616 | 0 | binding | down-regulates | 0.713 | Irak3 exerts negative regulatory effects through preventing (i) the dissociation of irak1 and irak4 from myd88 irak3 negatively regulates irak signalling through suppression of irak4 and irak1 activation | SIGNOR-205434 |
Q06413 | P56524 | 0 | binding | down-regulates | 0.713 | We discovered that mef2 interacts with histone deacetylases (hdacs) 4 and 5, resulting in repression of the transcriptional activity of mef2. | SIGNOR-76234 |
Q99705 | P20382 | 0 | binding | up-regulates | 0.713 | Here we show that the 353-amino-acid human orphan g-protein-coupled receptor slc-1 expressed in hek293 cells binds mch with sub-nanomolar affinity, and is stimulated by mch to mobilize intracellular ca2+ and reduce forskolin-elevated cyclic amp levels. | SIGNOR-69517 |
Q14623 | Q96QV1 | 0 | binding | down-regulates activity | 0.713 | Hip encodes a membrane glycoprotein that binds to all three mammalian hedgehog proteins with an affinity comparable to that of ptc-1. our findings support a model in which hip attenuates hedgehog signalling as a result of binding to hedgehog proteins: a negative regulatory feedback loop established in this way could thus modulate the responses to any hedgehog signal. | SIGNOR-65075 |
Q9H063 | P42345 | 0 | phosphorylation | down-regulates | 0.712 | The protein is phosphorylated mainly on residues s60, s68, and s75, and this inhibits its pol iii repression function. The responsible kinase is mtorc1, which phosphorylates maf1 directly. | SIGNOR-165795 |
Q13485 | P84022 | 0 | binding | up-regulates activity | 0.712 | TGF-² treatment initiates a kinase cascade that results in the phosphorylation of Smad3, followed by its heteromerization with Smad4 and subsequent translocation into the nucleus. | SIGNOR-235168 |
Q9Y6K1 | P01106 | 0 | binding | up-regulates activity | 0.712 | Based on one of these publications, we here showed that the interaction of Dnmt3a with c-myc promote the specific methylation of CG dinucleotides localized in c-myc boxes of promoter regions of CDKN2a, CCND1 and TIMP2 genes. Acellular experiments corroborated and complemented these results by revealing that the specificity of consensus sequence for DNA methylation of Dnmt3a is increased in presence of c-myc. | SIGNOR-255806 |
P61586 | Q9H8V3 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.712 | 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-260550 |
P05412 | P49841 | 0 | phosphorylation | down-regulates activity | 0.712 | The c-jun and c-myc oncogenic transcription factors are highly unstable proteins due to polyubiquitination. Similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation similar to c-myc, we report here that phosphorylation of c-jun by gsk3 creates a high-affinity binding site for the e3 ligase fbw7, which targets c-jun for polyubiquitination and proteasomal degradation.Phosphorylation of Thr-239 and Ser-243 is required for Fbw7-mediated c-Jun disappearance | SIGNOR-236717 |
O15105 | O15169 | 0 | binding | down-regulates | 0.712 | Here, we show that axin activates tgf-beta signaling by forming a multimeric complex consisting of smad7 and ubiquitin e3 ligase arkadia. | SIGNOR-145851 |
O75084 | O96014 | 0 | binding | up-regulates activity | 0.712 | Consistent with this, xfz7 biochemically and functionally interacts with xwnt11 | SIGNOR-78406 |
Q14145 | Q13501 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.712 | When autophagy is impaired, accumulated SQSTM1 interacts with KEAP1, leading to the proteasomal degradation of KEAP1. This interaction sequesters KEAP1 away from NFE2L2, preventing the ubiquitination and degradation of NFE2L2. Consequently, NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. | SIGNOR-279849 |
Q02078 | Q13164 | 0 | phosphorylation | up-regulates | 0.711 | We have previously shown that bmk1 regulates c-jun gene expression through direct phosphorylation and activation of transcription factor mef2c.Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b.The sites phosphorylated by activated bmk1 were mapped to ser-355, thr-312, and thr-319 of mef2a and ser-179 of mef2d both in vitro and in vivo. | SIGNOR-236579 |
Q96FF9 | P06493 | 0 | phosphorylation | down-regulates activity | 0.711 | Here we show that the mitotic kinases Aurora B and Cyclin-dependent kinase 1 (Cdk1) destabilize interactions between Sororin and the cohesin subunit precocious dissociation of sisters protein 5 (Pds5) by phosphorylating Sororin, leading to release of acetylated cohesin from chromosome arms and loss of cohesion. | SIGNOR-276118 |
P06239 | P22681 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.711 | Coexpression in 293T cells demonstrated that Lck kinase activity and Cbl ubiquitin ligase activity were essential for Lck ubiquitination and negative regulation of Lck-dependent serum response element-luciferase reporter activity. The Lck SH3 domain was pivotal for Cbl-Lck association and Cbl-mediated Lck degradation, with a smaller role for interactions mediated by the Cbl tyrosine kinase-binding domain. | SIGNOR-272614 |
Q12968 | P45984 | 0 | relocalization | down-regulates | 0.711 | Jnks directly phosphorylate nuclear factor of activated t-cell (nfat) transcription factors, thus antagonizing the effects of calcium-regulated signaling through the protein phosphatase calcineurin. | SIGNOR-103360 |
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