IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
O60674 | Q15910 | 1 | phosphorylation | down-regulates | 0.534 | Oncogenic y641 mutations in ezh2 prevent jak2/beta-trcp-mediated degradationbeta-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs beta-trcp-mediated ezh2 degradation. | SIGNOR-202711 |
Q9Y5B0 | P68400 | 0 | phosphorylation | down-regulates activity | 0.373 | We found that only phosphorylated FCP1 can physically interact with TFIIF. We set out to purify an FCP1 kinase from HeLa cells and identified casein kinase 2, which, surprisingly, displayed a negative effect on FCP1-associated activities.| Phosphorylation of FCP1 by CK2 Inhibits the Transcription Elongation Activity of FCP1. | Two in vivo phosphorylation sites within the C terminus of FCP1 at Ser-575 and Ser-740 were identified | SIGNOR-250844 |
P04637 | Q9BV47 | 0 | dephosphorylation | down-regulates activity | 0.366 | Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma|Inhibiting DUSP26 expression in the IMR-32 neuroblastoma cell line enhanced doxorubicin-induced p53 phosphorylation at Ser20 and Ser37, p21, Puma, Bax expression as well as apoptosis | SIGNOR-248765 |
P09874 | Q96EP1 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.427 | Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed. | SIGNOR-271470 |
Q13882 | P22681 | 1 | phosphorylation | down-regulates activity | 0.488 | Herein we report that PTK6 phosphorylates and down-regulates E3 ubiquitin ligase c-Cbl. | SIGNOR-279348 |
Q9Y259 | P17612 | 0 | phosphorylation | up-regulates activity | 0.253 | Choline kinase beta (CKbeta) is one of the CK isozymes involved in the biosynthesis of phosphatidylcholine. | This study provides evidence for CKβ phosphorylation by protein kinase A (PKA).|Phosphorylation sites were located on CKβ residues serine-39 and serine-40 as determined by mass spectrometry and site-directed mutagenesis. Phosphorylation increased the catalytic efficiencies for the substrates choline and ATP about 2-fold, without affecting ethanolamine phosphorylation, and the S39D/S40D CKβ phosphorylation mimic behaved kinetically very similar. | SIGNOR-275629 |
Q86WG3 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.378 | CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo. | SIGNOR-272651 |
P12931 | P04626 | 1 | phosphorylation | up-regulates activity | 0.615 | In addition, the c-Src inhibitor 4-(4\u2019-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2.|On the other hand, c-Src directly phosphorylates the cytoplasmic tails of both EGFR and HER2, allowing the binding of scaffold proteins that will further activate signal transduction. | SIGNOR-279432 |
Q15831 | Q8IWQ3 | 1 | phosphorylation | up-regulates | 0.503 | Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold | SIGNOR-122485 |
P05771 | P35548 | 1 | phosphorylation | up-regulates quantity | 0.322 | PKCbeta increased the level of overexpressed Msx2, but PKC alpha, delta and zeta did not have any significant effects.|Thr135 and Thr141 in Msx2 can be phosphorylated by PKC\u03b2, and Thr135 is important for regulating the protein stability of Msx2 by PKCs. | SIGNOR-278982 |
Q9BYX4 | O14730 | 0 | phosphorylation | down-regulates activity | 0.468 | RIOK3 mediates phosphorylation of MDA5 Ser-828|RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response | SIGNOR-264576 |
P22314 | P06493 | 0 | phosphorylation | up-regulates | 0.405 | Ubiquitin-activating enzyme, e1, is phosphorylated in mammalian cells by the protein kinase cdc2. Each serine residue was independently mutated to an alanine and analyzed by two-dimensional electrophoresis;only serine 4 was phosphorylated. Disruption of the basic amino acids within the nls resulted in loss of exclusive nuclear localization and a 90-95% decrease in the phosphorylation of ha1-e1 | SIGNOR-31157 |
P40763 | P51813 | 0 | phosphorylation | up-regulates activity | 0.6 | BMX activates STAT3 in glioblastoma stem cells.|BMX has previously been identified as an activator of STAT3, and BMX can phosphorylate STAT3 in vitro. | SIGNOR-279497 |
O60240 | P17612 | 0 | phosphorylation | down-regulates activity | 0.504 | PKA increased lipolysis in cells expressing Peri A because it abrogated the inhibitory actions of Peri A on lipolysis.‚ amino-terminal PKA sites (Ser-81, Ser-222, and Ser-276) | SIGNOR-250028 |
P43405 | P31995 | 1 | phosphorylation | up-regulates activity | 0.2 | Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation | SIGNOR-262675 |
P12931 | Q9Y3Q4 | 1 | phosphorylation | up-regulates | 0.371 | These results demonstrate that src tyrosine kinase enhances hcn4 currents by shifting their activation to more positive potentials and increasing the whole cell channel conductance as well as speeding the channel kinetics. The tyrosine residue that mediates most of src s actions on hcn4 channels is tyr531. | SIGNOR-158707 |
Q7Z434 | P00519 | 0 | phosphorylation | up-regulates activity | 0.453 | A phosphotyrosine specific antibody indicated that MAVS was phosphorylated by c-Abl. | SIGNOR-279673 |
P67775 | P06400 | 1 | dephosphorylation | up-regulates | 0.505 | This dephosphorylation returns prb to its active, growth suppressive state. | SIGNOR-75398 |
P24557 | Q16236 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.246 | Ecotopic expression of NF-E2 related factors showed that Nrf2, but not Nrf1, Nrf3, or Bach1, activated TXAS promoter in a dose-dependent manner. | SIGNOR-253907 |
P06241 | P11912 | 1 | phosphorylation | up-regulates activity | 0.596 | Lyn and Fyn phosphorylated the CD79a cytoplasmic portion of the fusion proteins well, with >80% of phosphorylation occurring at Y182. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM). | SIGNOR-251153 |
P18433 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.328 | In this process, PTPalpha Ser-180 and Ser-204 phosphorylation is critical for the induction of phosphatase activity, which is required for dephosphorylation of pp60(c-src). Taken together, we demonstrate the physical and functional association between PI 3-kinase, PKCdelta and PTPalpha in a signaling complex that mediates the antitumor activity of the somatostatin analogue TT-232. | SIGNOR-249113 |
Q13535 | P78527 | 1 | phosphorylation | up-regulates | 0.31 | Finally, in vitro atr-mediated phosphorylation at the t2609 cluster was further confirmed by western blot analysis using phosphospecific antibodies against t2647 (fig. ?(Fig.7e),7e), suggesting that dna-pkcs could be the direct target of atr kinase. | SIGNOR-148722 |
P49137 | P63104 | 1 | phosphorylation | down-regulates activity | 0.625 | We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. | SIGNOR-250151 |
P04637 | Q86Y07 | 0 | phosphorylation | up-regulates activity | 0.383 | Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells.|Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. | SIGNOR-280162 |
O95071 | P62837 | 0 | ubiquitination | up-regulates activity | 0.508 | Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. | SIGNOR-272668 |
P12931 | P46937-3 | 1 | phosphorylation | up-regulates activity | 0.632 | We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. | SIGNOR-274025 |
Q14161 | Q05209 | 0 | dephosphorylation | down-regulates | 0.344 | Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest. | SIGNOR-142719 |
P31749 | P55072 | 1 | phosphorylation | up-regulates | 0.509 | Site-directed mutagenesis identified ser-351, ser-745, and ser-747 as akt phosphorylation sites on vcp. however, our study also suggests that other known biological activities of vcp, such as those related to intracellular trafficking, ubiquitin-mediated proteolysis, and activation of transcription (28), might be regulated by akt through the activation of vcp. I | SIGNOR-252491 |
Q01860 | P27361 | 0 | phosphorylation | down-regulates | 0.343 | Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5. | SIGNOR-192101 |
Q07817 | P24941 | 0 | phosphorylation | up-regulates activity | 0.496 | Our findings show that Cdk2 phosphorylation of Bcl-xL at Ser73, but not the Bcl-xL cleavage products, is necessary and sufficient to induce cell death. | SIGNOR-278242 |
Q96SN8 | Q96R06 | 0 | relocalization | up-regulates activity | 0.465 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271719 |
P53539 | P68400 | 0 | phosphorylation | up-regulates | 0.2 | Our findings indicate that ck2 activation increases deltafosb's transactivation potential, while ck2 inhibition decreases it. Further, we show that preventing ser27 phosphorylation by mutating the site to ala results in a significant decrease in deltafosb transactivation | SIGNOR-152403 |
P38398 | Q03468 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.441 | BRCA1 polyubiquitinates CSB and this polyubiquitination and subsequent degradation of CSB occur following UV irradiation, even in the absence of Cockayne syndrome A (CSA) protein. | SIGNOR-272754 |
O15519 | Q13490 | 0 | ubiquitination | down-regulates quantity | 0.663 | Moreover, API-1 increased c-FLIP ubiquitination and decreased c-FLIP stability.|Thus, we conclude that API-1 reduces c-FLIP levels by facilitating its degradation through the ubiquitin and proteasome dependent pathway. | SIGNOR-278687 |
Q07912 | P40763 | 1 | phosphorylation | up-regulates activity | 0.286 | Since STAT1 and STAT3 are structurally related [3], we also assessed if ACK1 could induce the phosphorylation of STAT3 at residue Y705 (p-STAT3).|Our work demonstrates that catalytically active ACK1 can promote the activation of STAT1 and STAT3.|Here we demonstrate that catalytically active ACK1 induces the tyrosine phosphorylation of STAT1 and STAT3. | SIGNOR-279312 |
P17612 | O95180 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity. | SIGNOR-263110 |
Q96PY6 | P48163 | 1 | phosphorylation | down-regulates activity | 0.2 | PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation. | SIGNOR-275570 |
P49715 | P17947 | 1 | 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 |
P16220 | P23560 | 1 | transcriptional regulation | up-regulates quantity | 0.488 | Brain-derived neurotrophic factor (BDNF) is a critical molecule for learning and memory. Brain BDNF levels correlate with cognitive status. Activation of CREB facilitates the transcription of crucial proteins for activity-dependent plasticity particularly BDNF. | SIGNOR-265062 |
O14920 | Q92574 | 1 | phosphorylation | down-regulates | 0.642 | Here we show that ikkbeta, a major downstream kinase in the tnfalpha signaling pathway, physically interacts with and phosphorylates tsc1 at ser487 and ser511, resulting in suppression of tsc1phosphorylation of tsc2 (by akt and erk;refs. 28, 29) and tsc1(by ikkbeta;ref. 30) results in the disruption of the tsc1/2 complex, and thereby activates the oncogenic mtor signaling contributing to tumor progression. | SIGNOR-157296 |
P05019 | Q9UBK2 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.34 | PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy | SIGNOR-256152 |
Q92918 | Q13233 | 1 | phosphorylation | up-regulates | 0.455 | Hpk1 binds and phosphorylates mekk1 directly, | SIGNOR-43996 |
P53355 | P10586 | 0 | dephosphorylation | up-regulates | 0.2 | Lar tyrosine phosphatase dephosphorylates dapk at py491/492 to stimulate the catalytic, proapoptotic, and antiadhesion/antimigration activities of dapk | SIGNOR-157706 |
Q99558 | O43318 | 0 | phosphorylation | up-regulates activity | 0.564 | The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway|Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway. | SIGNOR-262833 |
P43694 | Q4G0P3 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | HYDIN promotes expression of Gata4 in cardiomyocyte differentiation. HYDIN functions as a positive regulator of human cardiomyocyte differentiation and promotes expression of cardiac contractile genes in hESC cells. This is mediated through GATA4, a critical transcription factor in heart development. Cardiac-specific Hydin knockdown in vivo leads to Gata4 downregulation and enhanced atrial septal defect (ASD) risk in mice. GATA4 is a fundamental TF in embryonic heart development and cardiac differentiation, and reduction in GATA4 function results in a diverse range of CHDs | SIGNOR-265479 |
Q9BQ15 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.501 | Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. | SIGNOR-262639 |
O60729 | P12830 | 1 | dephosphorylation | up-regulates activity | 0.313 | Cdc14B activates APC/C Cdh1 after DNA damage in G2.|Importantly, after DNA damage, thein vivo phosphorylation of wild type Cdh1 - but not that of Cdh1 (4xA) - increased after Cdc14B silencing (XREF_FIG), indicating that in response to genotoxic stress, Cdc14B dephosphorylates Cdh1 on the four sites phosphorylated by Cdk2. | SIGNOR-277017 |
P10636 | P07384 | 0 | cleavage | down-regulates activity | 0.333 | Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains | SIGNOR-251584 |
O00303 | Q7Z6M2 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Mediation of eIF3-f polyubiquitination by the SCFMAFbx. The association of MAFbx with the essential Skp1, Roc 1 and Cul1 proteins, specific components of an E3 ubiquitin–protein ligase (SCFMAFbx), was previously described. Here, we present evidence that during muscle atrophy MAFbx targets the eukaryotic initiation factor 3 subunit 5 (eIF3-f) for ubiquitination and degradation by the proteasome. | SIGNOR-271768 |
Q9UPW6 | P43354 | 1 | transcriptional regulation | down-regulates quantity | 0.295 | Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development | SIGNOR-268930 |
P56945 | P10586 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.339 | LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. | SIGNOR-276998 |
P27361 | C9JLW8 | 1 | phosphorylation | down-regulates activity | 0.2 | When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications.| While substitution of S4 or S18 with Ala did not affect the phosphorylation of MCRIP1 by ERK, substitution of either S21 or T30 significantly reduced MCRIP1 phosphorylation | SIGNOR-264772 |
Q99490 | Q00535 | 0 | phosphorylation | up-regulates | 0.262 | Here, we demonstrate that cyclin dependent kinase 5 (cdk5), a protein known to function mainly in postmitotic neurons, directly phosphorylates pike-a at ser-279 in its gtpase domain in glioblastoma cells. This phosphorylation event stimulates pike-a gtpase activity and the activity of its downstream effector akt. | SIGNOR-178660 |
P62714 | Q8WUI4 | 1 | dephosphorylation | up-regulates activity | 0.2 | Phosphorylation of conserved serine residues triggers association with 14-3-3 proteins and cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of their target genes. |Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3-3 binding sites in class IIa HDACs. | SIGNOR-248605 |
P27361 | O43561 | 1 | phosphorylation | down-regulates | 0.304 | Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway. | SIGNOR-125770 |
Q15139 | Q9Y3E5 | 1 | phosphorylation | up-regulates | 0.3 | Overexpression of constitutively active pkd or pkd activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (ser5 and ser87) in a form of bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic bit1 | SIGNOR-180085 |
P29350 | P24941 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.287 | Interaction between SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated Cdk2 phosphorylated SHP-1 protein. | SIGNOR-279147 |
Q9UNE7 | P54252 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.51 | Although our data show that CHIP may associate with Atx3 to ubiquitinate Atx3 in vitro, we still wonder whether CHIP is directly involved in the degradation of Atx3.|As a result, silencing of CHIP significantly increases the amount of Atx3 (XREF_FIG), suggesting that CHIP may down-regulate the Atx3 level. | SIGNOR-278667 |
P29323 | Q92823 | 1 | phosphorylation | up-regulates activity | 0.298 | EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase. | SIGNOR-262863 |
P49841 | P12036 | 1 | phosphorylation | down-regulates | 0.302 | Gsk3beta was shown to phosphorylate at ser-493 in vitro by phosphopeptide mapping and site-directed mutagenesis, and in vivo in hek293 cells. The role of ser-493 phosphorylation is also a question to be addressed in the future. Because the e-segment appears to be involved in filament formation (27, 42), phosphorylation in that region may also play a regulatory role in filament formation. Secondary structure prediction suggests that phosphorylation of ser-493 in combination with following the pro residue interrupts _-helix of the e-segment | SIGNOR-90668 |
P05129 | O15530 | 0 | phosphorylation | up-regulates | 0.2 | One of the most studiedevents controlled by ptdins(3,4,5)p3, comprises the activation of aof agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum- and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. | SIGNOR-126072 |
Q13309 | P31749 | 0 | phosphorylation | down-regulates activity | 0.515 | We further show that Akt1 phosphorylates Skp2 at Ser72, which is required to disrupt the interaction between Cdh1 and Skp2. | SIGNOR-278274 |
O43524 | Q13131 | 0 | phosphorylation | up-regulates activity | 0.517 | Phosphorylation by AMPK leads to the activtion of FOXO3 transcriptional activity without affecting FOXO3 subcellular localization. | SIGNOR-249684 |
P31751 | Q2PPJ7 | 1 | phosphorylation | down-regulates activity | 0.453 | RGC2 is an endogenous substrate for Akt2 downstream of PI 3-kinase | SIGNOR-269799 |
O14757 | Q9HC98 | 1 | phosphorylation | down-regulates activity | 0.237 | Nek6 is also directly phosphorylated by the checkpoint kinases Chk1 and Chk2 in vitro . | SIGNOR-279403 |
O14559 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.444 | 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-260491 |
P13807 | P49840 | 0 | phosphorylation | down-regulates | 0.411 | Glycogen synthase kinase-3 (gsk-3) phosphorylates four serine residues in the cooh terminus of glycogen synthase. Phosphorylation of one of these residues, ser640 (site 3a), causes strong inactivation of glycogen synthase | SIGNOR-118927 |
Q7Z2Y5 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Our results indicate that Nrk is ubiquitinated by CHIP in a chaperone-dependent manner, resulting in its proteasomal degradation. | SIGNOR-274110 |
P42684 | P46108 | 1 | phosphorylation | down-regulates | 0.695 | Abl2 kinase activity toward crk leads to increased phosphorylation of crk, inhibiting this cytoskeletal regulator by promoting intramolecular over intermolecular associations. | SIGNOR-136958 |
Q12923 | P35568 | 1 | dephosphorylation | down-regulates activity | 0.466 | Finally, we report that PTPL1 expression is sufficient to block the IRS-1/phosphatidylinositol 3-kinase/Akt signaling pathway, to inhibit the insulin-like growth factor-I effect on cell survival, and to induce apoptosis.|We first show by complementary approaches that PTPL1 specifically dephosphorylates insulin receptor substrate-1 (IRS-1) in vitro and in cellulo. | SIGNOR-277053 |
Q06481 | P45983 | 0 | phosphorylation | up-regulates | 0.362 | Phosphorylation at the thr(668) residue of app (with respect to the numbering conversion for the app 695 isoform) and the thr(736) residue of aplp2 (with respect to the numbering conversion for the aplp2 763 isoform) in their cytoplasmic domains acts as a molecular switch for their protein-protein interaction and is implicated in neural function(s) and/or alzheimer's disease pathogenesis. Here we demonstrate that both app and aplp2 can be phosphorylated by jnk at the thr(668) and thr(736) residues, respectively, in response to cellular stress. | SIGNOR-122196 |
Q9Y478 | O75385 | 1 | phosphorylation | up-regulates | 0.537 | Ampk and ulk1 interact and that the latter is phosphorylated by ampk. This phosphorylation leads to the direct activation of ulk1 by ampk bypassing mtor-inhibition | SIGNOR-173044 |
P63261 | P29350 | 0 | dephosphorylation | down-regulates | 0.2 | Our data suggest that shp-1 plays a pivotal role in reorganization of cytoskeletal architecture inducing actin dephosphorylation. These results clearly demonstrate the direct interaction of shp-1 with actin | SIGNOR-99565 |
Q9Y463 | Q9UQL6 | 1 | phosphorylation | down-regulates activity | 0.372 | Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent mannermirk phosphorylates hdac5 at ser-279 | SIGNOR-235809 |
P24928 | O60885 | 0 | phosphorylation | up-regulates | 0.448 | We report that brd4 is an atypical kinase that binds to the carboxyl-terminal domain (ctd) of rna polymerase ii and directly phosphorylates its serine 2 (ser2) sites both in vitro and in vivo under conditions where other ctd kinases are inactive. our findings may provide a mechanistic basis for several functional studies that showed that loss of brd4 causes transcription termination and embryonic lethality | SIGNOR-197012 |
Q92598 | P68400 | 0 | phosphorylation | down-regulates activity | 0.329 | Protein kinase CK2 phosphorylates Hsp105 alpha at Ser509 and modulates its function. | the phosphorylation of Hsp105 alpha at Ser(509) abolished the inhibitory activity of Hsp105 alpha in vitro. | SIGNOR-250901 |
P43250 | Q01726 | 1 | phosphorylation | down-regulates activity | 0.313 | Overexpression of GRK6 Inhibits Agonist-Induced cAMP Production in HBL Human Melanoma Cells, without Affecting MC1R Gene Expression | SIGNOR-252389 |
Q05397 | O14965 | 0 | phosphorylation | up-regulates activity | 0.255 | A schematic of regulation between these three kinases is shown in XREF_FIG, suggesting that Src was the upstream kinase regulating both FAK and AURA, whereas FAK might be downstream of AURA (as AURA phosphorylation of FAK yielded more incorporation of [32 P] gammaATP compared to FAK phosphorylation of AURA).|The effect of AURA on cell migration is augmented in the presence of Src and, in return, AURA also activates FAK. | SIGNOR-280188 |
O60260 | P38936 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Next, we defined whether pJNK is involved in parkin mediated p21 degradation.|Parkin ubiquitinates p21 in vivo and in vitro in an E3 ligase-substrate dependent manner. | SIGNOR-278640 |
P08151 | P17612 | 0 | phosphorylation | down-regulates | 0.551 | We report that activation of PKA retains Gli1 in the cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation of Gli1.We provide direct evidence to support that the cAMP/PKA signaling axis regulates Gli1 protein localization primarily through a site at Thr374. .These data suggest that Thr374 is an important PKA site responsible for PKA phosphorylation and for the transcriptional activity of Gli1. | SIGNOR-253539 |
O60674 | P04049 | 1 | phosphorylation | up-regulates activity | 0.617 | JAK2 phosphorylated Raf-1. e sites at 340/341 are indeed phosphorylated by JAK2 and that this phosphorylation represents a major component of the activation process. | SIGNOR-251361 |
Q99814 | O94953 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a. | SIGNOR-271584 |
Q9NRY6 | Q05655 | 0 | phosphorylation | up-regulates | 0.457 | Ad198-activated pkc-delta induces phosphorylation of mitochondrial pls3 at thr21;pls3 is a critical downstream effector of pkc-delta in ad198-induced apoptosis. | SIGNOR-140759 |
P51608 | Q9H2X6 | 0 | phosphorylation | up-regulates activity | 0.478 | Here, we identify the homeodomain-interacting protein kinase 2 (HIPK2) as a kinase that binds MeCP2 and phosphorylates it at Ser 80 in vitro and in vivo. | SIGNOR-264549 |
P00533 | Q9UK17 | 1 | phosphorylation | up-regulates activity | 0.2 | Our results demonstrate that human atrial I(to) and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue|We found that human atrial I(to) was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. | SIGNOR-275549 |
P00519 | P42684 | 1 | phosphorylation | up-regulates | 0.517 | The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization | SIGNOR-134396 |
P78347 | Q06187 | 0 | phosphorylation | up-regulates activity | 0.517 | These residues, tyr248, tyr357, and tyr462, were also found to be the major sites for btk-dependent phosphorylation of bap/tfii-i in vivo. Residues tyr357 and tyr462 are contained within the loop regions of adjacent helix-loop-helix-like repeats within bap/tfii-i. Mutation of either tyr248, tyr357, or tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type bap/tfii-i in transfected cos-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation. | SIGNOR-108346 |
Q99497 | P31749 | 0 | phosphorylation | up-regulates activity | 0.465 | Using a proteomic approach, we identified on DJ-1 a novel threonine phosphorylation (T125) that was found, by the in-silico tool scansite 4, as part of a putative Akt consensus. |Deglycase activity of DJ-1 on histones proteins, investigated by coupling 2D tau gel with LC-MS/MS and 2D-TAU (Triton-Acid-Urea)-Western blot, was found correlated with its phosphorylation status that, in turn, depends from Akt activation. | SIGNOR-275582 |
P17612 | P61586 | 1 | phosphorylation | down-regulates activity | 0.518 | PKA phosphorylates RhoA on Ser188. the addition of a negative charge to Ser188 is sufficient to diminish both RhoA activation and activity within the context of a cell. | SIGNOR-250047 |
Q96SN8 | Q9P209 | 0 | relocalization | up-regulates activity | 0.663 | By bringing CDK5RAP2 to the centrosome, the centriolar satellite proteins CEP72 and SPAG5 are required for the centrosomal localization of the other three MCPH proteins despite not interacting with them biochemically. | SIGNOR-271720 |
O43516 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.324 | TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation. | These results suggest that phosphorylation at S488 disrupts WIP binding to WASP. | SIGNOR-249181 |
O14757 | O14974 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | MYPT1 is phosphorylated by CDK1, thus recruiting protein phosphatase 1β (PP1cβ) to dephosphorylate and inactivate Plk1. Here we identified that Chk1 directly interacts with MYPT1 and preferentially phosphorylates MYPT1 at Ser20, which is essential for MYPT1-PP1cβ interaction and subsequent Plk1 dephosphorylation. | SIGNOR-277870 |
P31749 | P98177 | 1 | phosphorylation | down-regulates | 0.763 | Foxo4 transcription factor, also referred to afx, contains three putative phosphorylation motif sites for protein kinase b (pkb), thr32, ser197, and ser262, and it is proposed that phosphorylated foxo4 stays in the cytosol and is imported to the nucleus through dephosphorylation to induce target gene expression | SIGNOR-252486 |
P45452 | P02671 | 1 | cleavage | down-regulates quantity by destabilization | 0.2 | Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain | SIGNOR-263613 |
Q05655 | P06239 | 0 | phosphorylation | up-regulates activity | 0.526 | The tyrosine phosphorylation sites of PKC delta in the H(2)O(2)-treated cells were identified as Tyr-311, Tyr-332, and Tyr-512 by mass spectrometric analysis with the use of the precursor-scan method and by immunoblot analysis with the use of phosphorylation site-specific antibodies. Tyr-311 was the predominant modification site among them. In an in vitro study, phosphorylation at this site by Lck, a non-receptor-type tyrosine kinase, enhanced the basal enzymatic activity and elevated its maximal velocity in the presence of diacylglycerol. phosphorylation at Tyr-311 between the regulatory and catalytic domains is a critical step for generation of the active PKC delta in response to H(2)O(2). | SIGNOR-251386 |
P22607 | Q6N021 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.25 | FGFR3∆7-9, but not wild-type FGFR3, directly interacts with TET2 and phosphorylates TET2 at Y1902 site, leading to the ubiquitination and proteasome-mediated degradation of TET2. | SIGNOR-277535 |
P01189 | P41145 | 1 | chemical activation | up-regulates activity | 0.652 | Accordingly, for the OTDP, the binding affinity and activity of a large number of opiate compounds have been tested at μ-, δ-, and κ-opiate receptors. Binding studies were originally conducted in guinea pig brain membranes, and subsequent studies have been carried out in CHO cells transfected with human receptors. Table 7 shows a biochemical method for determining activity and potency of opioid compounds, stimulation of [35S]GTPγS binding in membranes from cells transfected with human μ, δ, or κ receptors. | SIGNOR-258410 |
Q14194 | Q00535 | 0 | phosphorylation | up-regulates | 0.622 | These findings suggest that sema3a-induced spine development is regulated by phosphorylation of crmp1 by cdk5. Introduction of crmp1-wt, but not crmp1-t509a/s522a, a crmp1 mutant that cannot be phosphorylated by cdk5, rescued the defect in sema3a responsiveness. | SIGNOR-159314 |
Q969T4 | P25963 | 1 | sumoylation | up-regulates quantity by stabilization | 0.346 | In the presence of an E1 SUMO-1-activating enzyme, Ubch9 conjugated SUMO-1 to IkappaBalpha primarily on K21, which is also utilized for ubiquitin modification. Thus, SUMO-1-modified IkappaBalpha cannot be ubiquitinated and is resistant to proteasome-mediated degradation. | SIGNOR-270545 |
P78527 | P07949 | 0 | phosphorylation | up-regulates activity | 0.27 | Phosphorylation of DNA-PKcs at s2056 is elevated in RET expressing cells and can be reduced by RET inhibition. | SIGNOR-279275 |
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