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 |
|---|---|---|---|---|---|---|---|
P08151 | O43312 | 0 | binding | up-regulates | 0.543 | Mim is a shh-responsive gene that can potentiate gli transcriptional activity.MIM Appears to regulate target gene expression through its association with the gli complex | SIGNOR-157650 |
Q8IVT5 | P15531 | 0 | phosphorylation | down-regulates | 0.543 | Autophosphorylated recombinant nm23-h1 phosphorylated ksr in vitro. Using site-directed mutagenesis, we found that nm23-h1 phosphorylated ksr serine 392, a 14-3-3-binding site, consistent with the recent identification of c-tak1 as a kinase for this site. | SIGNOR-90390 |
Q9H3D4 | P00519 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.543 | In cell lines, upon cisplatin treatment, c-Abl phosphorylates TAp63 on specific tyrosine residues. Such modifications affect p63 stability and induce a p63-dependent activation of proapoptotic promoters. | SIGNOR-260934 |
Q5BJF6 | P06493 | 0 | phosphorylation | up-regulates activity | 0.543 | Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles. | SIGNOR-273584 |
Q13322 | P07949 | 0 | binding | up-regulates | 0.543 | Grb7 and grb10, likely relay signals emanating from ret to other, as yet, unidentified targets within the cell | SIGNOR-41699 |
P67809 | Q15418 | 0 | phosphorylation | up-regulates | 0.543 | We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue. | SIGNOR-182497 |
P63096 | P41143 | 0 | binding | up-regulates activity | 0.543 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256683 |
Q13362 | P46695 | 0 | binding | down-regulates | 0.542 | Iex-1 binds to b56 subunits and perk independently, enhances b56 phosphorylation by erk at a conserved ser/pro site in this complex and triggers dissociation from the catalytic subunit. | SIGNOR-144309 |
P50148 | P25101 | 0 | binding | up-regulates | 0.542 | The response to endothelin-1 (et-1) consisted of two phases in both cell types. The initial, transient phase of contraction and phosphorylation of 20-kda myosin light chain (mlc20) was mediated additively by eta and etb receptors and initiated by galphaq-, ca2+/calmodulin-dependent activation of mlc kinase. | SIGNOR-129817 |
O43516 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.542 | Based on previous reports and the present data we suggest that Btk can induce WASP activation and also facilitates its subsequent inactivation through WIP phosphorylation.|We confirmed that Btk can indeed phosphorylate Y468 of baculovirus-generated human His-tagged WIP ( xref ), but that this is more difficult to show in cell extracts where WIP would be purified along with cellular WASP (). | SIGNOR-279801 |
P25963 | Q9UKB1 | 0 | ubiquitination | down-regulates | 0.542 | We report here the identification of an ikappab-ubiquitin (ub) ligase complex containing the f-box/wd40-repeat protein, beta-trcp, a vertebrate homolog of drosophila slimb. beta-trcp binds to ikappabalpha only when the latter is specifically phosphorylated by an ikappab kinase complex. here we provide evidence that lysine residues 21 and 22 serve as the primary sites for signal-induced ubiquitination of i kappa b alpha. | SIGNOR-64317 |
Q92934 | P17612 | 0 | phosphorylation | down-regulates | 0.542 | Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo. | SIGNOR-67387 |
O75030 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.542 | More interestingly, ERK-dependent phosphorylation of MITF at Ser 73 is essential for MITF ubiquitinilation and degradation (87). Putting together all these findings, it can be proposed that MAPK activation inhibits melanogenesis due to an increased MITF degradation which is dependent on the MAPK-induced MITF phosphorylation and ubiquitinilation. In summary, although the phosphorylation of MITF at Ser73 increases its intrinsic transcriptional activity, this phosphorylation also targets MITF to the proteasome for its degradation. Consequently, the decrease in MITF levels leads to a down-regulation of melanogenic enzymes expression and to an inhibition of melanogenesis. | SIGNOR-249620 |
P12931 | Q05209 | 0 | dephosphorylation | up-regulates activity | 0.542 | PTP-PEST increases dephosphorylation of Src at Y527 and activates it.|The data presented here supports our hypothesis that PTP-PEST activates Src via dephosphorylating it at Y527 (Tyr530 in human c-Src equivalent to Tyr527 in chicken Src). | SIGNOR-277086 |
Q9GZV5 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.542 | PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting the binding to the SCF E3 ubiquitin ligase. | SIGNOR-277116 |
P15336 | P53778 | 0 | phosphorylation | up-regulates | 0.542 | Our results indicate that atf-2 not only directly binds to smad3/4 hetero-oligomers but also that atf-2 is phosphorylated by tgf-beta signaling via tak1 and p38. The two pathways, smad and tak1, synergistically enhance the activity of atf-2 which acts as their common nuclear target | SIGNOR-65589 |
Q92934 | Q9Y243 | 0 | phosphorylation | down-regulates | 0.542 | Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155. | SIGNOR-81122 |
Q9Y2X7 | P12931 | 0 | phosphorylation | up-regulates activity | 0.542 | Tyrosines 246 and 293 are required to hold GIT1 in a closed conformation.Hyperphosphorylation of GIT1-N by Src and pervanadate does not affect its binding in vitro to full length GIT1 proteins. Mutations Y246E and Y293E of GIT1 enhance binding to paxillin. | SIGNOR-276627 |
P04150 | P27361 | 0 | phosphorylation | down-regulates | 0.542 | Cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK) phosphorylate the rat glucocorticoid receptor in vitro at distinct sites that together correspond to the major phosphorylated receptor residues observed in vivo; MAPK phosphorylates receptor residues threonine 171 and serine 246, whereas multiple CDK complexes modify serines 224 and 232.|MAPKs and CDKs exert opposite effects on receptor transcriptional enhancement. From our results, we speculate that activators of the MAPK pathway, such as growth factors, insulin, and certain oncoproteins, or inhibitors of CDK function, such as tumor growth factor beta (TGF_), p21, and p27, might attenuate receptor-induced transcrip- tional responses. In contrast, negative regulators of MAPK, such as pKA, as well as activators of CDK, such as the cyclins or CAKs, should potentiate receptor action. | SIGNOR-154409 |
Q13233 | Q9UPT6 | 0 | binding | up-regulates | 0.542 | Overexpression of full-length jsap1 in cos-7 cells led to a considerable enhancement of jnk3 activation, and modest enhancement of jnk1 and jnk2 activation, by the mekk1-sek1 pathwaythe regions of jsap1 that bound jnk, sek1, and mekk1 were distinct from one another. Jnk and mekk1 also bound jsap1 in vitro, suggesting that these interactions are direct. | SIGNOR-71471 |
P29597 | Q8N6P7 | 0 | binding | up-regulates | 0.542 | Il-22 activates jak1 and tyk2 | SIGNOR-90165 |
Q96T58 | Q99708 | 0 | binding | down-regulates | 0.542 | We identify the ctip and ctbp corepressors as novel components of the human rbp-jk/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. | SIGNOR-141616 |
Q9NUW8 | Q13315 | 0 | phosphorylation | up-regulates | 0.542 | Optimal function of the dna repair enzyme tdp1 requires its phosphorylation by atm and/or dna-pk. Here we show that top1-associated dna double-stranded breaks (dsbs) induce the phosphorylation of tdp1 at s81. This phosphorylation is mediated by the protein kinases: ataxia-telangiectasia-mutated (atm) and dna-dependent protein kinase (dna-pk) | SIGNOR-188772 |
O75581 | Q9UBV4 | 0 | binding | up-regulates | 0.542 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131677 |
P11021 | Q9UBS3 | 0 | binding | up-regulates activity | 0.542 | When BAP was added to BiP (2:1 molar ratio of BAP:BiP), it increased the ATPase activity of BiP by about 2-fold, which was similar to the increase observed when the J domain of ERdj4 was added to BiP (Fig.5). When both BAP and the J domain were added to BiP, the rate of ATP hydrolysis by BiP was stimulated by about 4-fold over basal levels, indicating that both BAP and ERdj4 positively regulate the ATPase activity of BiP | SIGNOR-261044 |
P01137 | P05412 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.542 | MAPKs have cis-acting regulatory elements in the mouse-TGF promoter region, which respond to various transcription factors, including specificity protein-1 and activating protein 1. Thus, it is possible that apoptotic cell-induced TGF-beta mRNA expression is mediated through activation of these transcription factors via MAPK signaling. Xiao et al. reported that all of the MAPK members, including p38/ERK/JNK, are required for apoptotic Jurkat cells up-regulation of TGF-beta production | SIGNOR-251713 |
P24928 | Q14004 | 0 | phosphorylation | up-regulates activity | 0.541 | Together, these studies demonstrate the important, yet largely redundant, role for CDK12 and CDK13 for the regulation of POLII CTD phosphorylation at multiple residues, as well as the global role for both of these kinases in regulating POLII occupancy across the genome.|CDK12 and CDK13 are thus evolutionarily related and structurally similar kinases, and biochemical assays have demonstrated that both have POLII C-terminal domain (CTD) kinase activity and the ability to phosphorylate the Ser2 residue of the repetitive CTD heptad sequence | SIGNOR-273054 |
P06127 | P06239 | 0 | phosphorylation | up-regulates activity | 0.541 | Tyrosine phosphorylation of cd5 requires lck activity. We propose that t cell activation mediates cd5 tyrosine phosphorylation at residues y429 and y463 mainly through the activation of lck | SIGNOR-106799 |
P08754 | P21554 | 0 | binding | up-regulates activity | 0.541 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256867 |
O43306 | P63096 | 0 | binding | down-regulates activity | 0.541 | Types V and VI adenylyl cyclase are most sensitive to inhibition by Gnai1, Gnai2, and Gnai3 | SIGNOR-278077 |
P25963 | O14965 | 0 | phosphorylation | down-regulates activity | 0.541 | The results of the in vitro kinase assay, using purified human recombinant AURKA and IkappaBalpha proteins, confirmed that AURKA can directly phosphorylate IkappaBalpha (Ser32) at a concentration as low as 2.5 ng/mul (XREF_FIG).|While an earlier study suggested that AURKA down-regulates IkappaBalpha indirectly through activation of the PI3K and AKT pathway 35, our data demonstrate, for the first time, that AURKA directly binds and phosphorylates the IkappaBalpha subunit, leading to activation of NF-kappaB. | SIGNOR-278912 |
P63096 | P21554 | 0 | binding | up-regulates activity | 0.541 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-256724 |
P63000 | Q13459 | 0 | gtpase-activating protein | down-regulates activity | 0.541 | 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-260510 |
Q13568 | Q9UHD2 | 0 | phosphorylation | up-regulates | 0.541 | Activation of interferon regulatory factor 5 by site specific phosphorylation. Although the gene induction by irf5 in the presence of tbk-1 was modest, phosphorylation by tbk-1 produced a significant shift in the mobility of irf5 in sds-page. For this reason we identified the residues that are phosphorylated on irf5 by tbk-1 with mass spectrometry. Ser-158 and ser-309 were found to be phosphorylated | SIGNOR-196528 |
Q13469 | P45984 | 0 | phosphorylation | down-regulates | 0.541 | 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-118223 |
Q96RR4 | P0DP24 | 0 | binding | up-regulates | 0.541 | The ca2+-calmodulin-dependent protein kinase (cam kinase) cascade includes three kinases: cam-kinase kinase (camkk);and the cam kinases camki and camkiv, which are phosphorylated and activated by camkk. | SIGNOR-266329 |
O60716 | P28827 | 0 | dephosphorylation | down-regulates quantity | 0.541 | Specifically, RPTP\u03bc dephosphorylated p120 catenin, subsequently leading to a lower level of cytoplasmic protein compared with that observed with the vector control and RPTP\u03bc-CS. | SIGNOR-277042 |
P24928 | Q96HW7 | 0 | binding | up-regulates activity | 0.541 | The Integrator Complex Can Directly Associate with the C-Terminal Domain of RNA Polymerase II Largest Subunit | SIGNOR-261185 |
P19838 | O00221 | 0 | binding | down-regulates | 0.541 | Nf-kb is normally sequestered in the cell cytoplasm by binding to ikbx, ikbb, ikbe | SIGNOR-102774 |
P04150 | P53041 | 0 | dephosphorylation | down-regulates activity | 0.541 | Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation.|Inhibition of GR phosphorylation at Ser-211 is associated with decreased nuclear retention of GR and decreased gene transcription. | SIGNOR-248538 |
Q9HAU4 | Q9Y3C5 | 0 | binding | up-regulates activity | 0.54 | RNF11 recruits AMSH to Smurf2 E3 ligase. Smurf2 promotes ubiquitination of AMSH in the presence of wt RNF11. Previously, we have shown that RNF11 interacts with the HECT-type E3 ligases AIP4 and Smurf2. Here, we show that RNF11 binds to AMSH in mammalian cells and that this interaction is independent of the RNF11 RING-finger domain and the PY motif. Our results also demonstrate that AMSH is ubiquitinated by Smurf2 E3 ligase in the presence of RNF11 and that a consequent reduction in its steady-state level requires both RNF11 and Smurf2. RNF11 therefore recruits AMSH to Smurf2 for ubiquitination, leading to its degradation by the 26S proteasome. | SIGNOR-272952 |
P15172 | Q02363 | 0 | binding | down-regulates activity | 0.54 | Id1 and Id2 interacted strongly with MyoD and Myf-5.Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-240268 |
Q9UNH5 | P06493 | 0 | phosphorylation | up-regulates activity | 0.54 | We found that Cdc14A is phosphorylated on Ser411, Ser453 and Ser549 by Cdk1 early in mitosis and becomes dephosphorylated during late mitotic stages. | SIGNOR-278264 |
P10275 | Q15910 | 0 | binding | up-regulates activity | 0.54 | This study demonstrates that phosphorylation of EZH2 at Ser21, mediated directly or indirectly by the PI3K-Akt pathway, can switch its function from a Polycomb repressor to a transcriptional coactivator of AR (and potentially other factors). | SIGNOR-251542 |
P46527 | P62258 | 0 | binding | down-regulates | 0.54 | 14-3-3_, 14-3-3_, and 14-3-3_ (but not 14-3-3_ and 14-3-3_) could form a complex with p27kip1 / we discovered that akt-mediated p27kip1phosphorylation directly induces p27kip1binding to 14-3-3 and cytoplasmic localization through phosphorylating the newly identified thr198residue. | SIGNOR-88297 |
Q8IWJ2 | P51151 | 0 | null | up-regulates activity | 0.54 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253087 |
Q9UNE7 | Q99933 | 0 | binding | up-regulates activity | 0.54 | BAG-1 stimulates CHIP-induced degradation of the glucocorticoid hormone receptor (GR). A model for the cooperation of CHIP and BAG-1 in coupling Hsc/Hsp70 to the ubiquitin/proteasome system. CHIP associates with Hsc/Hsp70 via its TPR chaperone adaptor (TPR) and, at the same time, recruits E2 ubiquitin-conjugating enzymes of the Ubc4/5 family to the chaperone complex. BAG-1 binds to Hsp70 via its BAG domain (BAG) and utilizes its ubiquitin-like domain (ubl) for proteasomal association | SIGNOR-272587 |
Q15042 | Q8TDJ6 | 0 | binding | up-regulates quantity | 0.54 | We isolated here a novel protein that was co-immunoprecipitated with Rab3 GEP and GAP by their respective antibodies from the crude synaptic vesicle fraction of rat brain. The protein, named rabconnectin-3, bound both Rab3 GEP and GAP. These results indicate that rabconnectin-3 serves as a scaffold molecule for both Rab3 GEP and GAP on synaptic vesicles. | SIGNOR-265582 |
P17302 | Q13164 | 0 | phosphorylation | down-regulates activity | 0.54 | Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC. | SIGNOR-250115 |
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 |
Q13546 | O15111 | 0 | phosphorylation | down-regulates activity | 0.54 | Indeed, IKKa and IKKb may directly repress RIPK1 kinase activity by addition of an inhibitory phosphate group on RIPK1.|Mass spectrometry analysis of kinase assays performed with recombinant proteins allowed us to identify Ser166, Ser331, and Ser416 as highly conserved RIPK1 residues phosphorylated by IKKa and IKKb. | SIGNOR-278927 |
Q16552 | P51449 | 0 | transcriptional regulation | up-regulates | 0.54 | We found that RORgt is required for the constitutive expression of IL-17 in intestinal lamina propria T cells and for the in vitro differentiation of Th17 cells from naive CD4+ T cells | SIGNOR-255029 |
P12931 | Q12923 | 0 | dephosphorylation | down-regulates activity | 0.54 | Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1 dependent dephosphorylation of Src at the activation loop.|Our results reveal a novel Src inactivation cycle in which reversion-induced LIM preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. | SIGNOR-277125 |
Q13153 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.54 | Our previous work revealed that the neuronal p35/Cdk5 kinase associates with Pak1 in a RacGTP-dependent manner, causing hyperphosphorylation and down-regulation of Pak1 kinase activity. We have now demonstrated direct phosphorylation of Pak1 on threonine 212 by the p35/Cdk5 kinase. | SIGNOR-249328 |
P01106 | P50750 | 0 | phosphorylation | down-regulates activity | 0.54 | CDK9 promotes phosphorylation of MYC on Ser 62 . | SIGNOR-279024 |
P26678 | Q09013 | 0 | phosphorylation | up-regulates | 0.54 | Coimmunoprecipitation studies showed that dmpk and pln can physically associate. Furthermore, purified wild-type dmpk, but not a kinase-deficient mutant (k110a dmpk), phosphorylates pln in vitro | SIGNOR-131371 |
P06737 | Q16816 | 0 | phosphorylation | up-regulates activity | 0.54 | It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15 | SIGNOR-267399 |
Q9NRF2 | P04629 | 0 | binding | up-regulates | 0.54 | The adapter protein sh2-b has been shown to bind to activated nerve growth factor (ngf) receptor trka and has been implicated in ngf-induced neuronal differentiation and the survival of sympathetic neurons. | SIGNOR-124198 |
Q96EB6 | Q13627 | 0 | phosphorylation | up-regulates activity | 0.54 | DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. | SIGNOR-278473 |
Q01970 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.539 | PKG can directly phosphorylate PLC-beta2 and PLC-beta3 in vitro with purified proteins and in vivo with metabolic labeling. Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated PLC-beta3 activity by 50-70% in COS-7 cell transfection assays. By using phosphopeptide mapping and site-directed mutagenesis, we further identified two key phosphorylation sites for the regulation of PLC-beta3 by PKG (Ser(26) and Ser(1105)). Mutation at these two sites (S26A and S1105A) of PLC-beta3 completely blocked the phosphorylation of PLC-beta3 protein catalyzed by PKG. | SIGNOR-249077 |
Q05682 | P28482 | 0 | phosphorylation | down-regulates | 0.539 | Extracellular signal-regulated kinases (erks) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-cad) at two sites (ser(759) and ser(789)) during smooth muscle stimulation. Nmr spectroscopy shows that the actin binding properties of the minimal inhibitory region of caldesmon, residues 750-779, alter upon map kinase phosphorylation of ser-759, a residue not involved in actin binding. This phosphorylation leads to markedly diminished actin affinity as a result of the loss of interaction at one of the two sites that bind to f-actin. | SIGNOR-71037 |
P33076 | P42224 | 0 | transcriptional regulation | up-regulates | 0.539 | When IFN-γ binds to its receptor, the receptor-associated protein tyrosine kinases Janus kinase I (JAK1) and JAK2 are activated (37). This leads to the phosphorylation of STAT1, which then dimerizes, translocates to the nucleus, and activates its target promoters, including the pIV promoter of Ciita | SIGNOR-256249 |
P51587 | P53350 | 0 | phosphorylation | down-regulates activity | 0.539 | M phase-specific phosphorylation of brca2 by polo-like kinase 1 correlates with the dissociation of the brca2-p/caf complex.Plk1 interacts with brca2 in vivo, and mutation of ser193, ser205/206, and thr203/207 to ala in br-n1 abolished plk1 phosphorylation, suggesting that brca2 is the substrate of plk1 | SIGNOR-102486 |
Q08828 | P38405 | 0 | binding | up-regulates activity | 0.539 | D1-class dopamine receptors (D1 and D5) activate the G s/olf family of G proteins to stimulate cAMP produc tion by AC and are found exclusively postsynaptically on dopamine-receptive cells, such as GABA-ergic medium spiny neurons (MSNs) in the striatum. | SIGNOR-264992 |
Q9H461 | Q9ULT6 | 0 | ubiquitination | down-regulates quantity | 0.539 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260111 |
Q969Q1 | P61088 | 0 | ubiquitination | up-regulates activity | 0.539 | We used MuRF1 as the E3 as it functions with all these E2s to ubiquitinate one of its typical substrates, troponin I Although UbcH1 and UbcH13/Uev1a support ubiquitination of troponin I by MuRF1, these E2s do not support ubiquitination of S5a, unlike Class I E2s. | SIGNOR-272737 |
P05067 | P78536 | 0 | cleavage | up-regulates activity | 0.539 | By the use of gene disruption (knockout), we now demonstrate that TACE (tumor necrosis factor alpha converting enzyme), a member of the ADAM family (a disintegrin and metalloprotease-family) of proteases, plays a central role in regulated alpha-cleavage of APP. Our data suggest that TACE may be the alpha-secretase responsible for the majority of regulated alpha-cleavage in cultured cells. | SIGNOR-262829 |
O75717 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.539 | And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. | SIGNOR-262664 |
P06400 | Q16539 | 0 | phosphorylation | down-regulates | 0.539 | P38 bypasses the cell cycle-associated hierarchical phosphorylation and directly phosphorylates rb on ser567, which is not phosphorylated during the normal cell cycle. Phosphorylation by p38, but not cdks, triggers an interaction between rb and the human homolog of murine double minute 2 (hdm2), leading to degradation of rb, release of e2f1 and cell death. | SIGNOR-168178 |
O43303 | P41002 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.539 | Using a mode of substrate binding distinct from other F-box protein-substrate pairs, CP110 and Cyclin F physically associate on the centrioles during the G2 phase of the cell cycle, and CP110 is ubiquitylated by the SCF(Cyclin F) ubiquitin ligase complex, leading to its degradation. | SIGNOR-266364 |
Q96CV9 | P53350 | 0 | phosphorylation | up-regulates | 0.539 | Here we show that at mitotic entry, plk1 phosphorylates optineurin (optn) at serine 177 and that this dissociates optn from the golgi-localized gtpase rab8, inducing its translocation into the nucleus. | SIGNOR-196367 |
Q16643 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.539 | Phosphorylation of drebrin at S142 by Cdk5 relieves the intramolecular inhibition of F-actin bundling. | SIGNOR-279452 |
P06239 | P41240 | 0 | phosphorylation | down-regulates | 0.538 | P50csk tyrosine kinase phosphorylates p56lck at tyr-505 and down regulates its catalytic activity. | SIGNOR-20371 |
Q9UM11 | P41002 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.538 | We show that cyclin F, a cell-cycle-regulated substrate receptor (F-box protein) for the SCF, is targeted for degradation by APC/C. Furthermore, we establish that Cdh1 is itself a substrate of SCF(cyclin F). Cyclin F loss impairs Cdh1 degradation and delays S-phase entry, and this delay is reversed by simultaneous removal of Cdh1. | SIGNOR-266363 |
Q06945 | O00560 | 0 | binding | up-regulates activity | 0.538 | Sox4 activation by IL-5R_ appears to be direct, with syntenin functioning as an adaptor molecule. Syntenin mediates IL-5induced Sox4 activation. | SIGNOR-223089 |
Q15797 | P35813 | 0 | dephosphorylation | down-regulates | 0.538 | In this study, we have found that ppm1a, a metal ion-dependent protein serine/threonine phosphatase, physically interacts with and dephosphorylates smad1 both in vitro and in vivo. considering the highly conserved nature of the sxs motif in all r-smads, we reasoned that ppm1a might also recognize the sxs motif in the bmp-activated smad1. | SIGNOR-149077 |
P00519 | P12931 | 0 | phosphorylation | up-regulates activity | 0.538 | c-Src-induced c-Abl activation involves phosphorylation of Y245 and Y412, two residues required for c-Abl mitogenic function. | SIGNOR-246311 |
P27986 | Q02763 | 0 | binding | up-regulates activity | 0.538 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242634 |
Q9NZC9 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.538 | ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity. | SIGNOR-273516 |
Q8N0Z6 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.538 | Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. | SIGNOR-262645 |
Q13546 | Q6GQQ9 | 0 | deubiquitination | down-regulates activity | 0.538 | NF-kappaB Suppression by the Deubiquitinating Enzyme Cezanne|Our study provides several lines of evidence to suggest that Cezanne suppresses TNFR signaling to NF-κB by targeting RIP1 for deubiquitination. | SIGNOR-268411 |
Q9Y253 | Q86YC2 | 0 | binding | up-regulates | 0.538 | Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates | SIGNOR-204541 |
P78527 | O00743 | 0 | dephosphorylation | up-regulates activity | 0.538 | In addition, siRNA knockdown of either PP6R1 or PP6 significantly decreased IR activation of DNA-PK, suggesting that PP6 activates DNA-PK by association and dephosphorylation.|PP6 may dephosphorylate sites in DNA-PKcs to reduce binding with heterodimer Ku proteins, because DNA-PK activation completely depends on Ku-mediated complex formation with DNA. | SIGNOR-277164 |
Q9NP62 | Q9UKT8 | 0 | binding | down-regulates quantity | 0.538 | FBW2 targets GCMa to the ubiquitin-proteasome degradation system. Here, we report the identification of an SCF complex as the GCM ubiquitin-protein isopeptide ligase (E3) that regulates human GCMa (hGCMa) degradation. We found that SKP1 and CUL1, two key components of the SCF complex, associate with hGCMa in vivo. We further identify the human F-box protein FBW2 (hFBW2) as the substrate recognition subunit in the SCF E3 complex for hGCMa. We show that hFBW2 interacts with hGCMa in a phosphorylation-dependent manner and promotes hGCMa ubiquitination. Supporting a critical role for hFBW2 in hGCMa degradation, knockdown of hFBW2 expression by RNA interference leads to a reduction in hGCMa ubiquitination and a concomitant increase in hGCMa protein stability. Our study identifies the SCF(hFBW2) E3 complex as the key machinery that targets hGCMa to the ubiquitin-proteasome degradation system | SIGNOR-271524 |
Q06413 | Q15759 | 0 | phosphorylation | up-regulates activity | 0.538 | In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2. | SIGNOR-280025 |
Q92843 | Q92934 | 0 | binding | down-regulates | 0.538 | Bad, however, bound tightly to bcl-2, bcl2l1, and bcl2l2. | SIGNOR-133805 |
P22914 | P02511 | 0 | binding | up-regulates activity | 0.538 | Human gamma-crystallins are long-lived, unusually stable proteins of the eye lens exhibiting duplicated, double Greek key domains. The lens also contains high concentrations of the small heat shock chaperone alpha-crystallin, which suppresses aggregation of model substrates in vitro. Mature-onset cataract is believed to represent an aggregated state of partially unfolded and covalently damaged crystallins. The alphaB-crystallin oligomers formed long-lived stable complexes with their gammaD-crystallin substrates. These in vitro results provide support for protein unfolding/protein aggregation models for cataract, with alpha-crystallin suppressing aggregation of damaged or unfolded proteins through early adulthood but becoming saturated with advancing age. | SIGNOR-253623 |
Q05397 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.538 | We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade.| PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. | SIGNOR-248661 |
P67809 | P51812 | 0 | phosphorylation | up-regulates | 0.538 | We therefore conclude that rsk1/rsk2 are novel activators of yb-1, able to phosphorylate the serine 102 residue. | SIGNOR-182165 |
Q12968 | Q08209 | 0 | dephosphorylation | up-regulates | 0.538 | Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat. | SIGNOR-176376 |
Q13950 | Q15797 | 0 | binding | up-regulates | 0.538 | Smad1 interacts with runx2 on the promoter of target genes and controls osteoblast gene expression and differentiation | SIGNOR-195642 |
P50458 | Q86U70 | 0 | binding | up-regulates activity | 0.538 | Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene. | SIGNOR-223962 |
P37231 | P35222 | 0 | binding | down-regulates activity | 0.538 | Oncogenic beta-catenin resists proteasomal degradation by inhibiting PPARgamma activity, which requires its TCF/LEF binding domain | SIGNOR-256072 |
Q13233 | Q13153 | 0 | phosphorylation | up-regulates activity | 0.538 | We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation. | SIGNOR-236006 |
P07948 | P41240 | 0 | phosphorylation | down-regulates | 0.538 | Lyn tyr507 kinase, csk, is recruited by pag, which targets lipid rafts by palmitoylation.Thus, our data suggest that il-6 treatment induces the translocation of cd45 to lipid rafts sequentially, followed by the association of cd45 with lyn and pag;dephosphorylation of lyn tyr507 and pag tyr314;lyn activation;and csk release from lipid rafts | SIGNOR-132912 |
Q13393 | Q15382 | 0 | binding | up-regulates | 0.537 | Rheb binds and activates pld1 in vitro in a gtp-dependent manner, strongly suggesting that pld1 is a bona fide effector for rheb. | SIGNOR-178892 |
P10071 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.537 | We show that these phosphoserines prime further phosphorylation at adjacent Glycogen Synthase Kinase 3 (GSK3) and Casein Kinase I (CK1) sites. Alteration of the GSK3 or CK1 sites prevents Ci-155 proteolysis and activates Ci in the absence of Hedgehog. | SIGNOR-219231 |
P62136 | Q9C0D0 | 0 | binding | up-regulates activity | 0.537 | Phactr-1 was previously identified as protein phosphatase 1 (PP1) α-interacting protein that possesses actin-binding domains. We showed that Phactr-1 depletion decreased PP1 activity, disrupted the fine-tuning of actin polymerization and impaired lamellipodial dynamics. Taken together our results strongly suggest that Phactr-1 is a key component in the angiogenic process. | SIGNOR-260062 |
Q9ULV8 | P12931 | 0 | phosphorylation | up-regulates | 0.537 | Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c. | SIGNOR-165862 |
P84022 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.537 | Smad3 was phosphorylated at both Ser203 and Ser207 in untreated MCF10CA1h cells and the p38 and ROCK inhibitors each down-regulated phosphorylation at these sites. we demonstrate that phosphorylation at Ser203 and Ser207 residues is required for the full transactivation potential of Smad3, and that these residues are targets of the p38 and Rho/ROCK pathways. | SIGNOR-250112 |
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