IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P10636 | Q9P0L2 | 0 | phosphorylation | down-regulates activity | 0.429 | We have studied the relationship between the phosphorylation of tau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. MARK and PKA phosphorylate several sites within the repeats (notably the KXGS motifs including Ser262, Ser324, and Ser356, plus Ser320). This type of phosphorylation strongly reduces tau's affinity for microtubules, and at the same time inhibits tau's assembly into PHFs. | SIGNOR-250173 |
P24752 | P48163 | 1 | acetylation | up-regulates activity | 0.249 | 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-275571 |
P51608 | P23560 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.471 | We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. | SIGNOR-264540 |
Q9UPS6 | P84243 | 1 | methylation | down-regulates activity | 0.2 | SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. | SIGNOR-265578 |
Q15831 | Q8TDC3 | 1 | phosphorylation | up-regulates | 0.485 | 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-122413 |
P43405 | P14317 | 1 | phosphorylation | up-regulates | 0.667 | Here, we show that bcr-associated tyrosine kinases lyn and syk synergistically phosphorylate hs1, and that tyr-378 and tyr-397 of hs1 are the critical residues for its bcr-induced phosphorylation. once the two tyrosine residues are both phosphorylated, processive phosphorylation of hs1 by lyn and the other src family kinases would take place, producing hyperphosphorylated form of hs1. Finally, it is this hyperphosphorylated form of hs1 that translocates to the nucleus and activates b cell apoptosis. | SIGNOR-47342 |
Q12929 | P27361 | 0 | phosphorylation | down-regulates activity | 0.323 | We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation. | SIGNOR-263058 |
Q13972 | P12931 | 0 | phosphorylation | down-regulates activity | 0.47 | These proximal Src kinases could potentially directly or indirectly phosphorylate Rasgrf-1 upon BCR activation and thereby further increase its GEF activity. | SIGNOR-280133 |
P15056 | P31751 | 0 | phosphorylation | down-regulates | 0.272 | We show that phosphorylation of b-raf by akt occurs at multiple residues within its amino terminal regulatory domain, at both the conserved and unique phosphorylation sites. Akt phosphorylated b-raf on s364 and s428 to inactivate its kinase activity b-raf contains three akt consensus sites, table i. One site, ser364 is conserved with c-raf;however, two sites, ser428 and thr439, are unique to b-raf | SIGNOR-78689 |
P31749 | O43464 | 1 | phosphorylation | down-regulates | 0.322 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-252500 |
P49841 | Q9Y243 | 0 | phosphorylation | down-regulates activity | 0.736 | Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1 | SIGNOR-245424 |
P16220 | O75676 | 0 | phosphorylation | up-regulates | 0.605 | Msk1 and msk2 directly phosphorilate and activete transcription factors such as creb1, atf1 msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. | SIGNOR-157158 |
Q16526 | Q13131 | 0 | phosphorylation | down-regulates | 0.384 | Ampk was shown to regulate the stability of the core clock component cry1 though phosphorylation of cry1 ser71, which stimulates the direct binding of the fbox protein fbxl3 to cry1, targeting it for ubiquitin-mediated degradation | SIGNOR-176472 |
Q86YJ5 | P10586 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271536 |
Q13950 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.367 | Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo. | SIGNOR-255777 |
Q96EB6 | P98177 | 1 | deacetylation | up-regulates | 0.744 | Deacetylation of foxos involves binding of the nad-dependent deacetylase hsir2(sirt1). Accordingly, hsir2(sirt1)-mediated deacetylation precludes foxo inhibition through acetylation and thereby prolongs foxo-dependent transcription of stress-regulating genes. | SIGNOR-124714 |
O75581 | P49674 | 0 | phosphorylation | up-regulates | 0.262 | We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo, | SIGNOR-145049 |
Q969P5 | P15172 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.56 | Here we present evidence that mafbx targets myod for degradation in several models of skeletal muscle atrophy. | SIGNOR-184861 |
Q16539 | Q9Y6W6 | 0 | dephosphorylation | down-regulates | 0.695 | Mkp-5 binds to p38 and sapk/jnk, but not to mapk/erk, and inactivates p38 and sapk/jnk, but not mapk/erk. p38 is a preferred substrate | SIGNOR-68983 |
Q92529-2 | P12931 | 0 | phosphorylation | up-regulates activity | 0.576 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273921 |
Q8TBB1 | Q9UMX1 | 1 | ubiquitination | down-regulates quantity | 0.2 | Indeed, they target different lysine residues in the SuFu protein, as LNX1 ubiquitinates SuFu at K59 and K470, and SCF Fbxl17 acts at K257, while Itch ubiquitinates at K321 and K457.|XREF_FIG, ectopic LNX1 expression reduced SuFu protein levels in HEK-293T cells, while shRNA mediated knockdown of LNX1 increased these levels. | SIGNOR-278626 |
P26599 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.438 | We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2, | SIGNOR-268689 |
P05787 | O75365 | 0 | dephosphorylation | down-regulates activity | 0.272 | the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL-3-interacting protein. Indeed, treatment with the PRL-3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431 | SIGNOR-248341 |
P28482 | Q13322 | 1 | phosphorylation | up-regulates | 0.373 | We show that grb10 is a direct substrate of the p42/44 mitogen-activated protein kinase (mapk)we identified ser(150), ser(418), and ser(476) of human grb10zeta as mapk-mediated in vitro phosphorylation sites. Replacing ser(150) and ser(476) with alanines reduced the inhibitory effect of human grb10zeta on insulin-stimulated irs1 tyrosine phosphorylation. Taken together, our findings suggest that phosphorylation of the adaptor protein may provide a feedback inhibitory mechanism by which grb10 regulates insulin signaling. | SIGNOR-138163 |
Q99704 | P06239 | 0 | phosphorylation | up-regulates activity | 0.6 | Phosphorylation of p56 dok and p62 dok is increased following CD2 stimulation and requires Lck. Phosphorylation of Dok proteins by Lck might provide a mechanism by which SH2-containing proteins can be recruited and co-localized with their substrates. | SIGNOR-251373 |
Q16665 | Q00535 | 0 | phosphorylation | up-regulates activity | 0.259 | In conclusion, we obtained compelling evidence that CDK5 directly stabilizes the transcription factor hypoxia inducible factor-1\u03b1 by phosphorylation, and thus promotes the formation of blood vessels.|Mass spectrometry and site directed mutagenesis revealed a stabilizing phosphorylation of HIF-1\u03b1 at Ser687 by CDK5. | SIGNOR-279020 |
Q16620 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.38 | Collectively, these data establish a direct enzyme-substrate interaction between PTP1B and phosphorylated Y705/706 (p-Y705/706) TRKB, the critical autophosphorylation sites that mediate BDNF-induced signaling.| Therefore, the data are consistent with a role of PTP1B as an inhibitor of BDNF/TRKB signaling | SIGNOR-264554 |
P16234 | Q05397 | 1 | phosphorylation | up-regulates activity | 0.429 | Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met. | SIGNOR-259400 |
P10276 | P50613 | 0 | phosphorylation | up-regulates | 0.546 | However, only the coexpression of cdk7 stimulated ser-77 phosphorylation in vivo and enhanced transactivation by rar alpha, but not by a s77a rar mutant. | SIGNOR-49693 |
Q13043 | Q9UL54 | 0 | phosphorylation | up-regulates | 0.279 | In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2 | SIGNOR-201330 |
P41161 | P63279 | 0 | sumoylation | down-regulates | 0.266 | Here we show that erm interacts with the sumo-conjugating enzyme ubc9 and is modified by sumo. We further show that sumo modification of this ets transcription factor affects its ability to activate transcription. | SIGNOR-135850 |
Q92529-2 | P00533 | 0 | phosphorylation | up-regulates activity | 0.617 | We also obtained tryptic phosphopeptide maps of N-Shc protein phosphorylated in vitro by other tyrosine kinases, TrkB, v-Src and EGFR. The overall patterns of the phosphopeptide maps generated by these tyrosine kinases were similar, although there were some differences among these maps (Figure 4a–d).We performed phosphopeptide mapping analysis using GST-fused N-Shc protein, and found that N-Shc phosphorylated by TrkA in vitro was resolved into at least seven phosphopeptides (Y1 through Y7, Figure 4a). Phosphopeptide mapping revealed that N-Shc has novel tyrosine-phosphorylation sites at Y259/Y260 and Y286; in vivo-phosphorylation of these tyrosines was demonstrated by site-specific anti-pTyr antibodies. Phosphorylated Y286 bound to several proteins, of which one was Crk. The pY221/pY222 site, corresponding to one of the Grb2-binding sites of Shc, also preferentially bound to Crk. The phosphorylation-dependent interaction between N-Shc and Crk was demonstrated in vitro and in vivo. | SIGNOR-273922 |
P23469 | Q14721 | 1 | dephosphorylation | down-regulates activity | 0.355 | Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon | SIGNOR-248450 |
P30086 | Q05655 | 0 | phosphorylation | up-regulates | 0.301 | Here we show that the raf kinase inhibitor protein (rkip) is a physiological inhibitor of grk-2. After stimulation of gpcr, rkip dissociates from its known target, raf-1 (refs 6-8), to associate with grk-2 and block its activity. This switch is triggered by protein kinase c (pkc)-dependent phosphorylation of the rkip on serine 153. | SIGNOR-119551 |
P45983 | Q00613 | 1 | phosphorylation | down-regulates activity | 0.497 | JNK is activated by heat shock and phosphorylates HSF-1 on serine 363. JNK Phosphorylation of HSF-1 Leads to Reduction in Its Transcriptional Activity | SIGNOR-250119 |
Q13352 | Q13153 | 0 | phosphorylation | up-regulates | 0.2 | Serine 28 phosphorylation of nrif3 confers its co-activator function for estrogen receptor-alpha transactivation. p21-activated protein kinase 1 (pak1) phosphorylates eralpha at ser305 and this modification is important in eralpha transactivation function. | SIGNOR-178795 |
Q02156 | P11362 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of serine 779 in fibroblast growth factor receptor 1 and 2 by protein kinase c(epsilon) regulates ras/mitogen-activated protein kinase signaling and neuronal differentiationour findings show that in addition to fgfr tyrosine phosphorylation, the phosphorylation of a conserved serine residue, ser(779), can quantitatively control ras/mapk signaling to promote specific cellular responses. | SIGNOR-201671 |
P00519 | Q00535 | 1 | phosphorylation | up-regulates activity | 0.585 | Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity. | SIGNOR-245288 |
Q9UBR4 | Q15319 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.398 | Using oligonucleotide microarrays to generate expression profiles of inner ears of Pou4f3(ddl/ddl) mutant and wild-type mice, we have identified and validated Lhx3, a LIM domain transcription factor, as an in vivo target gene regulated by Pou4f3. Lhx3 is a hair cell-specific gene expressed in all hair cells of the auditory and vestibular system as early as embryonic day 16. The level of Lhx3 mRNA is greatly reduced in the inner ears of embryonic Pou4f3 mutant mice. Our data also show that the expression of Lhx3 is regulated differently in auditory and vestibular hair cells. | SIGNOR-262586 |
P31995 | P43405 | 0 | 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 |
Q15418 | O14745 | 1 | phosphorylation | up-regulates activity | 0.33 | In summary, these results demonstrate that Ras-RSK1 signaling promotes nuclear localization of EBP50.|Specifically, RSK1 phosphorylates EBP50 at threonine 156 (T156) residue in a cell cycle dependent manner, which is important for nuclear translocation of EBP50 to facilitate cellular proliferation and transformation. | SIGNOR-278290 |
Q16695 | P41229 | 0 | demethylation | up-regulates activity | 0.2 | KDM5 subfamily is capable of removing tri†and di†methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing. | SIGNOR-264306 |
Q14457 | Q9NR19 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276561 |
P30519 | P69905 | 1 | null | down-regulates activity | 0.254 | Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular hemoprotein, hemoglobin, and heme | SIGNOR-251814 |
O14595 | Q15796 | 1 | dephosphorylation | down-regulates activity | 0.445 | Dephosphorylation of Smad2/3 Linkers by SCP2 and SCP3|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248299 |
Q15311 | P17252 | 0 | phosphorylation | up-regulates activity | 0.389 | In deletion mutant analyses of potential phosphorylation sites in RLIP76, we identified T297 and S509 as targets for phosphorylation by PKCalpha. Phosphorylation at T297 increased doxorubicin (DOX)-transport activity approximately 2-fold for RLIP76 purified from recombinant source | SIGNOR-263164 |
Q13535 | Q96RU2 | 1 | phosphorylation | up-regulates activity | 0.2 | Here we report that the deubiquitylase USP28 is recruited to sites of DNA damage in cisplatin-treated cells. ATR phosphorylates USP28 and increases its enzymatic activity.|Representative immunoblots of n = 3. C Immunoblotting of total and phosphorylated USP28 at serine 67 and 714 in A431 cells exposed to indicated concentrations of CPPD for 6 h. | SIGNOR-275850 |
P79483 | Q5T0T0 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271408 |
P46934 | P27216 | 0 | relocalization | up-regulates quantity | 0.344 | Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb. | SIGNOR-272571 |
P68431 | O94953 | 0 | demethylation | down-regulates activity | 0.2 | The KDM4 family of Jumonj domain histone demethylases specifically target di- and tri-methylated lysine 9 on histone H3 (H3K9me3), removing a modification central to defining heterochromatin and gene repression. The majority of studies regarding its function describe it as an activator that removes repressive H3K9me3 and H3K9me2 at or near regulated promoters in order to facilitate expression of the indicated pathways. | SIGNOR-263734 |
Q8WXE1 | Q13535 | 0 | phosphorylation | up-regulates | 0.878 | When dna is damaged, the atr-atrip complex is recruited to chromatin and is activated to transduce the checkpoint signal, but the precise kinase activation mechanism remains unknown. Here, we show that atrip is phosphorylated in an atr-dependent manner after genotoxic stimuli. The serine 68 and 72 residues are important for the phosphorylation in vivo and are required exclusively for direct modification by atr in vitro. | SIGNOR-129473 |
P68400 | O95786 | 1 | phosphorylation | down-regulates | 0.2 | Threonine at amino acid (aa) 770 and serine at aa 854 to 855 of rig-i are phosphorylated by casein kinase ii (ck2) in the resting state of the cell and dephosphorylated when cells are infected by rna virus. Mutation at aa position 770 or 854 to 855 of rig-i renders it constitutively active | SIGNOR-169404 |
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 |
P00533 | Q9UM47 | 1 | phosphorylation | up-regulates activity | 0.593 | Here, we report that treatment of EGFR mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH+ stem like cells through EGFR dependent activation of Notch3.|We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. | SIGNOR-280002 |
O95886 | Q9BYB0 | 1 | relocalization | up-regulates activity | 0.2 | SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3). | SIGNOR-264594 |
P38936 | Q06330 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.307 | Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J_ protein to the p21 promoter. | SIGNOR-252032 |
Q12933 | Q14164 | 0 | phosphorylation | up-regulates activity | 0.686 | IKKepsilon phosphorylates TRAF2 at Ser11 to activate NF-kappaB and promote malignant transformation. | SIGNOR-279195 |
Q9UPN3 | P49841 | 0 | phosphorylation | down-regulates activity | 0.435 | We discovered that GSK3β, a kinase inhibited by Wnt signaling, directly phosphorylates ACF7, a > 500 kDa microtubule-actin crosslinking protein abundant in hair follicle stem cells (HF-SCs). We map ACF7's GSK3β sites to the microtubule-binding domain and show that phosphorylation uncouples ACF7 from microtubules. | SIGNOR-264428 |
O60858 | P04234 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | RFP2, a gene frequently lost in various malignancies, encodes a protein with RING finger, B-box, and coiled-coil domains that belongs to the RBCC/TRIM family of proteins.Rfp2 Regulates the Stability of the ERAD Substrate CD3-δ. In summary, these experiments demonstrate that Rfp2 functions as a RING-dependent ERAD E3 ubiquitin ligase and regulates the degradation of the ER substrate, CD3-δ. | SIGNOR-271644 |
Q7Z6Z7 | O43474 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.34 | K48 linked KLF4 ubiquitination by E3 ligase Mule controls T-cell proliferation and cell cycle progression.|Instead, we identified the transcription factor KLF4 as a novel Mule substrate that is ubiquitinated by this E3 ligase and thus undergoes proteasomal degradation in T cells.|Here we report that Lys-48-linked ubiquitination of the transcription factor KLF4 mediated by the E3 ligase Mule promotes T-cell entry into S phase. | SIGNOR-278749 |
P01106 | P49761 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | C-Myc enhances transcriptional activation of CLK3 promoter in CCA cells. | SIGNOR-274123 |
O15530 | P05771 | 1 | phosphorylation | up-regulates | 0.522 | One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of 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-126069 |
Q14896 | P22694 | 0 | phosphorylation | up-regulates | 0.274 | Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human). | SIGNOR-163772 |
P53778 | P37198 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). | SIGNOR-277416 |
P01111 | P04049 | 1 | relocalization | up-regulates | 0.87 | The raf family of proteins (raf-1, a-raf, and b-raf) bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175231 |
P23025 | Q96EB6 | 0 | deacetylation | up-regulates activity | 0.511 | SIRT1 deacetylates XPA at residues K63, K67, and K215 to promote interactions with ATR | SIGNOR-262294 |
Q13263 | O96017 | 0 | phosphorylation | down-regulates activity | 0.411 | In particular, Chk2 phosphorylates KAP1 on Ser473 decreasing the interaction between KAP1 and HP1 proteins: this post translational modification promotes HP1\u03b2 mobilization and the reorganization of chromatin structure favoring the repair of DNA breaks inside heterochromatin [ , ].|Of note, phosphorylation of S473 by Chk2 decreases the interaction between KAP1 and HP1 proteins and is necessary for HP1\u03b2 mobilization, a key event for DNA repair in the heterochromatin [ - ]. | SIGNOR-279730 |
Q5T0T0 | P12830 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Inhibiting proteasome activity with MG132 prevented CDH1 and beta2M degradation, indicating that MARCH8 might be targeting CDH1 and beta2M for proteasomal degradation.|We demonstrated that MARCH8 interacts with and ubiquitinates CDH1 and beta2M. | SIGNOR-278820 |
P17612 | Q14500 | 1 | phosphorylation | down-regulates activity | 0.283 | Phosphorylation of the Kir2.2 C terminus by protein kinase A inhibited the association with SAP97.‚ | SIGNOR-249998 |
Q9H6L5 | Q13554 | 0 | phosphorylation | up-regulates activity | 0.2 | Under ER-stress conditions, activated CAMK2B phosphorylates the reticulon-homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER-phagy. | SIGNOR-273554 |
P20396 | P23769 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.263 | The rat prepro-TRH gene is activated by GATA2. | SIGNOR-267259 |
P00519 | P78337 | 1 | phosphorylation | up-regulates activity | 0.2 | Notably, c-Abl controls augmentation of Pitx1 at the post-transcriptional level.|Overexpression of c-Abl induces tyrosine phosphorylation of Pitx1, either directly or indirectly. | SIGNOR-280171 |
O43524 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.595 | Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway | SIGNOR-184569 |
Q8N695 | P17676 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription. | SIGNOR-254054 |
P53350 | P01106 | 1 | phosphorylation | up-regulates activity | 0.533 | Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency | SIGNOR-243522 |
O43172 | P21127 | 0 | phosphorylation | up-regulates activity | 0.2 | Furthermore, hPRP4 interacted directly with Clk1 on its COOH terminus, and the arginine and serine rich domain of hPRP4 was phosphorylated by Clk1 in vitro.|Overexpression of Clk1 caused redistribution of hPRP4, from the speckled to the diffuse pattern in nucleoplasm, whereas inactive mutant of Clk1 caused no change of hPRP4 localization. | SIGNOR-280208 |
Q12968 | P35354 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.279 | NFAT induces the transcription of the COX2 (cyclo-oxygenase-2) gene incancer cells thereby enhancing invasive migration | SIGNOR-264028 |
P62993 | P21802 | 0 | phosphorylation | up-regulates | 0.773 | Inhibition of basal fgf receptor signaling by dimeric grb2. | SIGNOR-197980 |
P46379 | P35558 | 1 | acetylation | down-regulates quantity by destabilization | 0.34 | These results indicate that BAT3 and P300 can both exist in the PEPCK1 protein complex, suggesting the possibility that BAT3 could be an enhancer of PEPCK1 acetylation. | indicating a synergistic effect of BAT3 and P300 to promote PEPCK1 acetylation. | SIGNOR-267598 |
P62745 | P48729 | 0 | phosphorylation | down-regulates | 0.2 | Mass spectrometry analysis demonstrates that rhob is monophosphorylated by ck1, in its c-terminal end, on serine 185. lastly we show that the inhibition of ck1 activates rhob and promotes rhob dependent actin fiber formation and egf-r level. | SIGNOR-179255 |
P46937 | O43318 | 0 | phosphorylation | down-regulates activity | 0.338 | TAK1 inhibits YAP activity through beta-TRCP.|Thus, our data indicate that TAK1 directly phosphorylates YAP at multiple sites.|These observations prompted us to test whether TAK1 phosphorylates YAP at S127. | SIGNOR-278956 |
Q13351 | P42773 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.266 | Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c. | SIGNOR-266046 |
P42771 | O14770 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We show that the Pbx1 and Meis2 homeodomain proteins interact with Klf4 and can be recruited to DNA elements comprising a Klf4 site or G C box, with adjacent Meis and Pbx sites. Meis2d and Pbx1a activate expression of p15(Ink4a) and E-cadherin, dependent on the Meis2d transcriptional activation domain. We suggest a model in which genes with Klf4 sites can be cooperatively activated by Meis2/Pbx1 and Klf4, dependent primarily on recruitment by Klf4. | SIGNOR-267240 |
Q9BZL6 | Q9UBF8 | 1 | phosphorylation | up-regulates | 0.2 | Binding of 14-3-3 proteins to pi4kiiibeta involved the pkd phosphorylation site ser294, evident from reduced 14-3-3 binding to a s294a pi4kiiibeta mutant. Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase iii beta protects from dephosphorylation and stabilizes lipid kinase activity. | SIGNOR-148880 |
O15379 | P12931 | 0 | phosphorylation | up-regulates activity | 0.385 | C-Src also phosphorylated three tyrosine sites of HDAC3 at tyrosine 325, 328, and 331. Importantly, wild-type c-Src increases HDAC3 activity, but not mutant c-SrcK298M (kinase inactive form). | SIGNOR-277485 |
Q92974 | P12931 | 0 | phosphorylation | up-regulates activity | 0.415 | Src activates GEF-H1. | SIGNOR-277478 |
Q86YJ5 | P18433 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. | SIGNOR-271540 |
Q15831 | Q9NRH2 | 1 | phosphorylation | up-regulates activity | 0.367 | We demonstrate that LKB1 activates SNRK by phosphorylating the T‐loop residue (Thr173) | SIGNOR-260824 |
Q96BR1 | Q86YD1 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36. | SIGNOR-279283 |
Q13131 | Q9BU19 | 1 | phosphorylation | down-regulates | 0.2 | Arebp is phosphorylated at ser(470) by ampk. Phosphorylation reduces the dna-binding activity of arebp. | SIGNOR-150590 |
P29474 | P62136 | 0 | dephosphorylation | up-regulates activity | 0.2 | The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation | SIGNOR-248558 |
Q9Y5Q3 | P49840 | 0 | phosphorylation | down-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159432 |
Q13480 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.38 | Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well.|The results indicate that PTP1B completely dephosphorylated Gab1 and the mutant protein failed to dephosphorylate Gab1 (Figure\u00a0 xref C). | SIGNOR-276965 |
P50548 | P28482 | 0 | phosphorylation | up-regulates | 0.596 | The experiments presented here indicate that erf is regulated during nuclear import and/or export and that this process depends on its phosphorylation by erks our analysis indicates that in addition to t526 (position 7), s161 (position 2), s246 (position 3), and s251 (position 4) are also phosphorylated in vitro by erk2 and in vivo after mitogenic stimulation (fig. 3a). | SIGNOR-67524 |
Q13555 | P00533 | 1 | phosphorylation | down-regulates activity | 0.362 | The mechanism of desensitization of kinase activity can be accounted for, in part, by the EGF-stimulated phosphorylation of the receptor at Ser1046/7, a substrate for the multifunctional calmodulin-dependent protein kinase II in vitro. Mutation of Ser1046/7 by replacement with Ala residues blocks desensitization of the EGF receptor protein-tyrosine kinase activity. | SIGNOR-250694 |
P31749 | Q13309 | 1 | 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 |
Q14524 | Q96BR1 | 0 | phosphorylation | up-regulates activity | 0.275 | Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5 | SIGNOR-275767 |
Q86UR1 | P27361 | 0 | phosphorylation | down-regulates | 0.267 | Accumulating evidence indicates that protein phosphorylation regulates nox activity. In this report, we show that serine282 residue of nox activator 1 (noxa1) is phosphorylated by erk in response to egf resulting in desensitization of nox1 activity | SIGNOR-164231 |
Q9BXM7 | Q9H300 | 0 | cleavage | down-regulates quantity by destabilization | 0.613 | Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy. | SIGNOR-261364 |
Q8TB45 | P43405 | 0 | phosphorylation | down-regulates activity | 0.2 | We found that tyrosine (Tyr) 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. Using proximity biotinylation assays, we identified SYK (spleen tyrosine kinase) as a kinase involved in DEPTOR Tyr 289 phosphorylation in an ephrin (erythropoietin-producing hepatocellular carcinoma) receptor-dependent manner. | SIGNOR-277572 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.