IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
O60674 | P41597 | 1 | phosphorylation | up-regulates activity | 0.605 | JAK2 phosphorylates CCR2 at the Tyr139 position and promotes JAK2/STAT3 complex association to the receptor. | SIGNOR-251345 |
O14746 | Q12986 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.52 | NFX1-123 positively regulated hTERT expression, as its knockdown decreased hTERT mRNA levels and telomerase activity and its overexpression increased telomerase activity. NFX1-123 was found to interact with cytoplasmic poly(A) binding proteins (PABPCs), and together they synergistically augmented expression from the hTERT promoter when activated by HPV16 E6. | SIGNOR-261050 |
P62714 | Q9BXL7 | 1 | dephosphorylation | down-regulates activity | 0.2 | NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. | SIGNOR-248607 |
O14874 | P12931 | 0 | phosphorylation | up-regulates activity | 0.2 | Src phosphorylated BCKDK at the tyrosine 246 (Y246) site in vitro and ex vivo. Knockdown and knockout of Src downregulated the phosphorylation of BCKDK. Importantly, phosphorylation of BCKDK by Src enhanced the activity and stability of BCKDK, thereby promoting the migration, invasion, and EMT of CRC cells. | SIGNOR-275583 |
P51948 | P03372 | 1 | phosphorylation | up-regulates activity | 0.397 | Human Estrogen Receptor α Is Phosphorylated at Serine 118 In Vivo by Cdk7 | SIGNOR-260837 |
Q9Y6K1 | P68400 | 0 | phosphorylation | down-regulates activity | 0.2 | This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. | SIGNOR-276650 |
P12931 | P63000 | 1 | phosphorylation | up-regulates activity | 0.615 | In addition, Rac1 is phosphorylated at Y64 by FAK and Src kinases ( xref ); Y64 phosphorylation targets Rac1 to focal adhesions. | SIGNOR-280132 |
P24723 | P09211 | 1 | phosphorylation | up-regulates activity | 0.2 | Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently | SIGNOR-276014 |
P51812 | Q92934 | 1 | phosphorylation | down-regulates | 0.385 | The rsks catalyze the phosphorylation of the pro-apoptotic protein bad at serine 112 to promote cell survival. | SIGNOR-184595 |
P41002 | P68400 | 0 | phosphorylation | down-regulates activity | 0.249 | We determined that casein kinase II (CK2) can phosphorylate Ser621 and thereby regulate the E3 ligase activity of the SCF(cyclin F) complex. | SIGNOR-266373 |
P11802 | Q8IZL8 | 1 | phosphorylation | up-regulates | 0.351 | Using site-directed mutagenesis and in vitro kinase assays, we identified ser(477) and ser(991) of pelp1 as cdk phosphorylation sites. we identified pelp1 as a novel substrate of cdks and found that cdk phosphorylation is important for the proper function of pelp1 in modulating hormone-driven cell cycle progression and also for optimal e2f transactivation function. | SIGNOR-167770 |
P43405 | O14757 | 0 | phosphorylation | down-regulates | 0.311 | We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation. | SIGNOR-197528 |
P32942 | Q04759 | 0 | phosphorylation | up-regulates activity | 0.334 | Ser489 was a phosphorylation site in vitro for recombinant protein kinase Ctheta. Finally, treatment of Jurkat cells with chelerythrine chloride, a protein kinase C inhibitor, prevented ICAM-3-triggered spreading. | SIGNOR-248979 |
Q8NBZ7 | P29320 | 0 | phosphorylation | up-regulates activity | 0.2 | However, it is possible that etk is a principal activator of Ugd.|The phosphorylation of the Ugd protein (a UDP-glucose dehydrogenase) by Etk increases Ugd dehydrogenase activity. | SIGNOR-280006 |
P07384 | P49840 | 1 | cleavage | up-regulates activity | 0.2 | Thus, it has been shown that calpain cleaves the inhibitory domain of GSK3 generating two fragments of 40 and 30 kDa. This cleavage enhanced activity of the kinase | SIGNOR-251585 |
Q9UBS0 | Q05195 | 1 | phosphorylation | down-regulates | 0.2 | In this study, we showed that mad1 is a substrate of p90 ribosomal kinase (rsk) and p70 s6 kinase (s6k). Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway | SIGNOR-178594 |
O43318 | Q86WV6 | 1 | phosphorylation | up-regulates activity | 0.2 | Activated TAK1 directly mediates STING phosphorylation on serine 355, which facilitates its interaction with STING ER exit protein (STEEP) and thereby promotes its oligomerization and translocation to the ERGIC for subsequent activation | SIGNOR-277887 |
P15173 | Q13683 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.283 | Only myogenin and MyoD were able to efficiently trans-activate the alpha7 promoter-CAT construct (Fig. 7). Myogenin trans-activated the promoter by _2-fold whereas MyoD was able to trans-activate by nearly 4-fold, indicating that both of these factors may play a role in alpha7 gene expression during muscle development. | SIGNOR-241521 |
P35568 | P18031 | 0 | dephosphorylation | down-regulates | 0.779 | Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. | SIGNOR-74852 |
Q9Y4K3 | Q9NQC7 | 0 | deubiquitination | down-regulates | 0.789 | The nf-kappab activation by cyld is mediated, at least in part, by the deubiquitination and inactivation of tnfr-associated factor 2 (traf2) and, to a lesser extent, traf6. | SIGNOR-117856 |
P0DPH8 | Q5SQI0 | 0 | acetylation | up-regulates quantity by stabilization | 0.242 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272246 |
P20336 | Q8WXG6 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.396 | Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP). | SIGNOR-265579 |
Q8IXH7 | Q05086 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.326 | In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level. | SIGNOR-271404 |
P12931 | Q9UK53 | 1 | phosphorylation | down-regulates activity | 0.367 | Src Decreases the Stability and Level of ING1.|This study, as well as a previous report identifying Ser-126 of ING1 as a kinase target, confirm that ING1 stability is also regulated by phosphorylation. However, the mechanism may be complex since phosphorylation of Ser-126 stabilizes the protein while phosphorylation by Src reduces ING1 stability and causes a relocalization of ING1 from the nucleus to the cytoplasm. | SIGNOR-279760 |
Q00987 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.537 | HIPK2 inhibits both MDM2 gene and protein by, respectively, p53-dependent and independent regulations.|This p53-independent effect is likely mediated by HIPK2 catalytic activity and we found that HIPK2 phosphorylates MDM2 in vitro. | SIGNOR-279465 |
P16949 | P17612 | 0 | phosphorylation | down-regulates | 0.309 | Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka). | SIGNOR-38318 |
P23396 | P27361 | 0 | phosphorylation | up-regulates | 0.351 | Erk phosphorylates threonine 42 residue of ribosomal protein s3. | SIGNOR-137175 |
Q14814 | Q13627 | 0 | phosphorylation | down-regulates activity | 0.411 | DYRK1A phosphorylates MEF2D and decreases its transcriptional activity | SIGNOR-277901 |
P49840 | P46531 | 1 | phosphorylation | down-regulates | 0.319 | Taken together, our results indicate that gsk-3alfa is a negative regulator of notch1/nicd. | SIGNOR-183969 |
Q16539 | P40763 | 1 | phosphorylation | up-regulates | 0.621 | All stats are phosphorylated on at least one serine residue in their tad specifically, ser727 in stats 1 and 3 and ser721 in stat4. Stat serine kinases have been identified through the use of inhibitors, dominant-negative alleles, and in vitro kinase assays. They include mapk (p38mapk: stats 1, 3, 4;erk: stat3, 5;jnk: stat3), pkc_ (stat1, stat3), mtor (stat3), nlk (stat3 (42)), and camkii and ikk_ (stat1 (39, 40, 43)).STAT Serine phosphorylation regulates transcriptional activity (see below). | SIGNOR-154783 |
Q16637 | Q86YT6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.324 | The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein | SIGNOR-253112 |
P24844 | Q5VT25 | 0 | phosphorylation | up-regulates | 0.516 | More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above. | SIGNOR-188781 |
Q13568 | O15111 | 0 | phosphorylation | down-regulates activity | 0.474 | These data indicate that in context of MyD88 signaling pathway IKKalpha suppresses IRF-5 activation.|These data showed that the IKK\u03b1 phosphorylates IRF-5 and that IKK\u03b1 mediated phosphorylation stimulates formation of IRF-5 dimers. | SIGNOR-278293 |
P78368 | P84022 | 1 | phosphorylation | down-regulates | 0.337 | Cki?2 Directly phosphorylates smad3 at ser418, leading to the increased ubiquitination and proteasomal degradation of activated smad3 following tgf-? Treatment. | SIGNOR-181069 |
Q8WZA2 | P01308 | 1 | relocalization | up-regulates quantity | 0.377 | Activation of EPAC2 has recently been shown to increase the density of insulin‐containing granules near the plasma membrane, facilitating insulin secretion from the β cells | SIGNOR-278140 |
Q8NEV1 | P00451 | 1 | phosphorylation | down-regulates activity | 0.2 | Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II-like kinase may downregulate the activity of the two cofactors.| Recombinant human factor VIII also showed incorporation of radioactivity in the presence of purified casein kinase II at the acidic NH2-terminal portion of factor VIII light chain (residues 1648 through 1689). Based on all the considerations reported above Se1657 is the most likely candidate within this region capable of incorporation of radioactivity | SIGNOR-263649 |
P06493 | Q9Y3Z3 | 1 | phosphorylation | down-regulates | 0.492 | Cyclin a2/cdk1 phosphorylates samhd1 at the threonine 592 residue both in vitro and in vivo. Phosphorylation of samhd1 thr592 correlates with loss of its ability to restrict hiv-1. | SIGNOR-201913 |
Q16549 | P28324 | 1 | phosphorylation | up-regulates | 0.2 | In contrast, the tcf sap-1a is efficiently phosphorylated by p38 map kinase in vitro and in vivo on the homologous residues ser381 and ser387 | SIGNOR-47771 |
P60484 | P19338 | 1 | dephosphorylation | up-regulates activity | 0.27 | The fact that PTEN\u03b2 interacts with nucleolin and dephosphorylates nucleolin at Thr84 raised a question as to whether nucleolin mediates PTEN\u03b2 regulation of rDNA transcription, and thus represents a direct mechanism by which PTEN\u03b2 controls ribosomal biogenesis. | SIGNOR-277166 |
O43524 | P04150 | 0 | transcriptional regulation | up-regulates quantity | 0.415 | We show that FOXO3 is an immediate early glucocorticoid receptor (GR) target, whose transcription is even further enhanced by conditions that mimic metabolic stress. | SIGNOR-255759 |
P19525 | P51812 | 0 | phosphorylation | up-regulates | 0.2 | Our data indicated that phosphorylation of pkr at thr(451) is mediated through erk2 and rsk2, but not through p38 kinase. | SIGNOR-154183 |
Q01973 | P12931 | 1 | phosphorylation | up-regulates | 0.318 | Ror1 binds to and phosphorylates c-src / ror1 kinase-dependent c-src activation | SIGNOR-196751 |
Q9NZJ5 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.267 | Finally, we demonstrated that wild-type PTP1B directly dephosphorylated myc-tagged PERK that had been isolated from tunicamycin-treated HEK293T cells by immunoprecipitation ( xref ).|The ability of PTP1B to dephosphorylate Tyr619 and inactivate PERK is fine tuned by the production of H 2 S by CSE in response to ER stress. | SIGNOR-277051 |
Q96J02 | Q15796 | 1 | ubiquitination | up-regulates | 0.453 | Itch promotes ubiquitination of smad2 and augments smad2 phosphorylation that requires an intact ligase activity of itch. Moreover, itch facilitates complex formation between tgf-beta receptor and smad2 and enhances tgf-beta-induced transcription. | SIGNOR-128647 |
Q9Y5P4 | P78368 | 0 | phosphorylation | down-regulates | 0.2 | These results indicate that ckigamma2 hyperphosphorylates the serine-repeat motif of cert, thereby inactivating cert and down-regulating the synthesis of sphingomyelin. | SIGNOR-182160 |
Q99683 | Q14680 | 0 | phosphorylation | up-regulates activity | 0.271 | MELK, as an upstream kinase of ASK1, phosphorylates threonine 838 in an activation loop of human ASK1, thereby stimulating ASK1 kinase activity. | SIGNOR-280039 |
P49840 | Q8NHW3 | 1 | phosphorylation | up-regulates activity | 0.2 | We also demonstrate that gsk-3 triggers mafa sequential phosphorylation on residues s61, t57, t53, and s49 /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./ Taken together, these results suggest that, in contrast to what can be expected from ubiquitination/degradation, gsk-3-mediated mafa phosphorylation increases its transactivating ability, thereby controlling its biological activity. | SIGNOR-159377 |
P35354 | P05112 | 1 | null | up-regulates | 0.444 | Cox2 Is a Direct Srf Target Gene and Controls Il4 Expression | SIGNOR-255967 |
Q16827 | P55072 | 1 | dephosphorylation | down-regulates activity | 0.423 | An important aspect of this study is that tyrosine dephosphorylation of VCP by PTPRO sensitizes HepG2 cells to Doxorubicin, a chemotherapeutic drug commonly used for a variety of cancers. | SIGNOR-277063 |
P30291 | P11308 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively. | SIGNOR-277529 |
P08670 | P17612 | 0 | phosphorylation | down-regulates activity | 0.309 | Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure. | SIGNOR-250068 |
O75116 | Q99962 | 1 | phosphorylation | down-regulates | 0.439 | We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85. | SIGNOR-140466 |
O95819 | Q15797 | 1 | phosphorylation | down-regulates activity | 0.2 | Msn kinases directly phosphorylate α-helix 1 of Smad. we have identified Misshapen (Msn) and the mammalian orthologs TNIK, MINK1, and MAP4K4 as the kinases responsible for α-helix 1 phosphorylation. | SIGNOR-276335 |
P10721 | P17252 | 0 | phosphorylation | down-regulates | 0.531 | Phosphorylation of kit/scfr by pkc-_ in vitro: identification of ser-741 and ser-746 as the major phosphorylation sites for pkc / pkc, which acts in an scf-stimulated feedback loop, that negatively controls kit/scfr kinase activity | SIGNOR-28605 |
P10275 | Q16512 | 0 | phosphorylation | up-regulates | 0.587 | Rho can sensitize the ar to low levels of circulating androgens by promoting the nuclear translocation of a transcriptional co-activator, fhl2 (four and a half lim domains 2), which binds ar, and by stimulating protein kinase n (pkn), which phosphorylates ar directly. | SIGNOR-152762 |
Q13177 | P12931 | 0 | phosphorylation | up-regulates | 0.562 | Pak2 became tyrosine phosphorylated in its n-terminal regulatory domain, where y130 was identified as the major phosphoacceptor site. Tyrosine phosphorylation-mediated superactivation of pak2 could be induced by overexpression of different src kinases or by inhibiting cellular tyrosine phosphatases with pervanadate and could be blocked by the src kinase inhibitor pp1 or by mutating the y130 residue. | SIGNOR-92460 |
P46527 | P49792 | 0 | relocalization | down-regulates quantity | 0.2 | RanBP2 can increase the sumoylation of p27kip1. In our study, the target protein p27kip1 mainly acts as a tumor-suppressor gene in the nucleus, RanBP2 and SUMO1 act as oncogenes by promoting the nuclear-cytoplasmic translocation and debilitate the G1-arrest brought by p27kip1 accumulation in the nucleus. | SIGNOR-259115 |
P41212 | O15550 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.3 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260032 |
Q13972 | P17612 | 0 | phosphorylation | up-regulates | 0.519 | Phosphorylation of serine 916 of ras-grf1 contributes to the activation of exchange factor activity by muscarinic receptors. | SIGNOR-73202 |
P11926 | P25054 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.268 | APC-dependent regulation of ornithine decarboxylase in human colon tumor cells|Upon induction of APC expression, ODC promoter activity and RNA levels were suppressed | SIGNOR-253670 |
P19838 | P62877 | 0 | ubiquitination | up-regulates | 0.451 | The scf-betatrcp complex is responsible for the ubiquitination of p100 and p105 following their phosphorylation by ikk. | SIGNOR-106781 |
Q9NYA1 | P28482 | 0 | phosphorylation | up-regulates | 0.561 | Activation of sphingosine kinase 1 by erk1/2-mediated phosphorylation. | SIGNOR-118546 |
O75581 | P27361 | 0 | phosphorylation | up-regulates | 0.313 | We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. | SIGNOR-169004 |
O15264 | P52564 | 0 | phosphorylation | up-regulates activity | 0.661 | p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation. | SIGNOR-273952 |
Q92837 | P17612 | 0 | phosphorylation | down-regulates | 0.2 | Phosphorylation of ser188 by pka inhibited the ability of frat1 to activate beta-catenin-dependent transcription. | SIGNOR-149689 |
Q8IXL6 | Q9GZV9 | 1 | phosphorylation | down-regulates activity | 0.64 | Here we show that Fam20C directly phosphorylates FGF23 on Ser(180) | Our above results support, phosphorylation of FGF23 at Ser180 inhibits O-glycosylation and would therefore promote hormone proteolysis and thus inactivation. | SIGNOR-260925 |
Q9H0Z9 | O15297 | 0 | dephosphorylation | up-regulates activity | 0.363 | Interestingly, we showed that PPM1D directly interacts with and dephosphorylates RBM38 at serine 195. | SIGNOR-277020 |
P31751 | P62714 | 0 | dephosphorylation | down-regulates | 0.481 | These results confirm that the activity changes observed are achieved by a reversible phosphorylation mechanism, and also argue that pp2a may negatively regulate rac-pk activity in vivo. Dephosphorylation of the activated rac-pk in itro by pp2ac resulted in an 87% reduction of kinase activity | SIGNOR-42123 |
Q96B36 | P31749 | 0 | phosphorylation | down-regulates activity | 0.782 | Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40 | SIGNOR-252544 |
Q7Z699 | P00533 | 0 | phosphorylation | down-regulates activity | 0.272 | We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions. | SIGNOR-273638 |
P19484 | P11279 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.441 | Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants | SIGNOR-276555 |
P18031 | P40763 | 1 | dephosphorylation | down-regulates activity | 0.552 | PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3. | SIGNOR-248427 |
O15550 | P11308 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our findings reveal a dual role for UTX in suppressing acute myeloid leukaemia via repression of oncogenic ETS and upregulation of tumor suppressive GATA programs. several ETS transcription factors, including Elf4, Etv6, Erg, Fli1, Ets2, Spi1 and Elk3 were upregulated immediately after Utx loss in the preleukaemic phase | SIGNOR-260033 |
Q969V6 | P28482 | 0 | phosphorylation | down-regulates | 0.2 | Serum induces rhoa-dependent translocation of mkl1 from the cytoplasm to the nucleus and also causes a rapid increase in mkl1 phosphorylation. Serum-induced phosphorylation of the serum response factor coactivator mkl1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization. | SIGNOR-195153 |
P60484 | Q9BXM7 | 0 | phosphorylation | down-regulates activity | 0.47 | PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import. | SIGNOR-277915 |
P0DOX6 | Q99856 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene. | SIGNOR-268532 |
Q7Z570 | Q6ZUJ8 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. ZNF804A was identified as a schizophrenia-associated gene by GWAS and was predicted to play a role in DNA binding and transcription To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3). | SIGNOR-269463 |
Q14114 | Q8WY64 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.444 | Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation. | SIGNOR-271486 |
Q05655 | P07550 | 1 | phosphorylation | down-regulates activity | 0.352 | We investigate the role of the beta 2-adrenergic receptor phosphorylation by protein kinase C in this regulatory process. Mutation of the serine-261, -262, -344 and -345 of the beta 2-adrenergic receptor prevented the phorbol-ester-induced phosphorylation of the receptor. This mutation also abolished the phorbol-ester-induced decrease in high-affinity agonist binding and potency of the beta 2-adrenergic receptor. We suggest that protein kinase C mediated phosphorylation of the receptor promotes its functional uncoupling. | SIGNOR-248855 |
Q15173 | O95235 | 1 | dephosphorylation | up-regulates activity | 0.2 | We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878. | SIGNOR-262660 |
P48730 | Q6U7Q0 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.2 | CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction. | SIGNOR-264892 |
Q96BR1 | Q9Y2I7 | 1 | phosphorylation | up-regulates activity | 0.461 | The Western blot in XREF_FIG demonstrates that SGK3 as well as PKB phosphorylate PIKfyve at position S318, thereby indicating that PIKfyve could be a physiological target of SGK3.|We here identify a novel mechanism involving NMDA receptor triggered, SGK3 dependent stimulation of PIKfyve with subsequent formation of PI (3,5) P 2, which modulates RAB11A facilitated vesicle transport to the plasma membrane, leading to an increased abundance of GluA1 receptor subunits in the plasma membrane. | SIGNOR-279113 |
O60674 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.377 | PTP-PEST-Containing Lysates from EGF-Treated HC11 Cells Dephosphorylate JAK2 More Efficiently than Lysates from Control Cells|phospho-JAK2-specific rabbit polyclonal antiserum (44-426, BioSource Technologies, Inc., Camarillo, CA) which recognizes Tyr1007/1008 in the activation site | SIGNOR-248657 |
O60716 | P28482 | 0 | phosphorylation | down-regulates activity | 0.27 | Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation. | SIGNOR-277505 |
P10242 | P68400 | 0 | phosphorylation | down-regulates activity | 0.34 | For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants. | SIGNOR-250918 |
Q9UKV5 | Q00535 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.248 | We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. | SIGNOR-277356 |
Q6IE81 | P48729 | 0 | phosphorylation | down-regulates activity | 0.277 | We demonstrate that the destruction complex component casein kinase 1α (CK1α) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit β-catenin signaling. | SIGNOR-273618 |
O00629 | P46531 | 1 | relocalization | up-regulates | 0.287 | Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7. | SIGNOR-165314 |
Q00535 | P40763 | 1 | phosphorylation | up-regulates | 0.402 | We report here that the cdk5/p35 complex associates with stat3 and phosphorylates stat3 on the ser-727 residue in vitro and in vivo. Ser phosphorylation of stat3 and transcription of stat3 target genes, such as c-fos and junb, in a cdk5-dependent manner. | SIGNOR-124325 |
Q9Y243 | Q9UKV8 | 1 | phosphorylation | up-regulates | 0.423 | Phosphorylation of argonaute 2 at serine-387 facilitates its localization to processing bodies, akt3-mediated phosphorylation of ago2 is a molecular switch between target mrna cleavage and translational repression activities of ago2 | SIGNOR-178416 |
Q07820 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.396 | TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers. | SIGNOR-278726 |
P53671 | Q5VT25 | 0 | phosphorylation | up-regulates activity | 0.395 | These results indicate that mrckalpha phosphorylates and activates lim kinases downstream of cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of adf/cofilin. | SIGNOR-107584 |
Q5JWF2 | P32245 | 0 | null | up-regulates activity | 0.521 | We hypothesize that XLαs may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus. | SIGNOR-253067 |
P23470 | P09619 | 1 | dephosphorylation | down-regulates activity | 0.338 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254715 |
P00519 | P00533 | 1 | phosphorylation | up-regulates | 0.419 | we show that activated Abl phosphorylates the EGFR primarily on tyrosine 1173Furthermore, we show that activated Abl allows the ligand-activated EGFR to escape Cbl-dependent down-regulation by inhibiting the accumulation of Cbl at the plasma membrane in response to epidermal growth factor stimulation and disrupting the formation of the EGFR.Cbl complex without affecting Cbl protein stability. These findings reveal a novel role for Abl in promoting increased cell-surface expression of the EGFR and suggest that Abl/EGFR signaling may cooperate in human | SIGNOR-149277 |
P19474 | Q9UJV9 | 1 | ubiquitination | down-regulates quantity | 0.638 | Furthermore, overexpression of TRIM21 in mDCs led to lower expression of DDX41 in these mDCs and up to 70% less IFN-beta production by mDCs in response to intracellular DNA (XREF_FIG).|Here we report that the E3 ligase TRIM21 negatively regulated the type I interferon response in myeloid dendritic cells (mDCs) and monocytes that had been induced by cytosolic double stranded DNA (dsDNA), mainly by promoting the ubiquitination and degradation of DDX41. | SIGNOR-278790 |
P08311 | P01024 | 1 | cleavage | up-regulates activity | 0.599 | Plasma membrane elastase and cathepsin G from U937 cells cleave C3 into C3a- and C3b-like fragments; further incubation leads to C3c- and C3dg-like fragments, as judged from SDS-PAGE analysis of the digests. Sequencing of the C3b-like fragment purified by reverse phase chromatography indicates that initial cleavage of C3 by purified cathepsin G occurs at two positions in the amino-terminal part of the alpha-chain, at a Arg-Ser bond located between residues 748 and 749 and at a Leu-Asp bond between residues 751 and 752. | SIGNOR-256348 |
P36897 | Q04771 | 1 | phosphorylation | up-regulates activity | 0.364 | This directly demonstrates that TGFBR1 can activate ACVR1 in vivo.|We show that in response to TGF-\u03b2, TGFBRI phosphorylates and activates ACVR1, which phosphorylates SMAD1/5. | SIGNOR-279490 |
P12931 | P19022 | 1 | phosphorylation | down-regulates | 0.397 | Src-mediated phosphorylation of the n-cadherin cytoplasmic domain results in a significant reduction in beta-catenin bindingbeta-catenin dissociates from n-cadherin and redistributes to the nucleus of transmigrating melanoma cells to activate gene transcription.Because there were only four tyrosine residues (y852, y860, y884, and y886) in this peptide, all of them were phosphorylated. | SIGNOR-143242 |
Q13490 | Q9Y385 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.37 | We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome. | SIGNOR-263092 |
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