IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P00519 | Q04912 | 0 | phosphorylation | up-regulates activity | 0.272 | This suggests that by interacting with Sdc4, either directly or indirectly, RON is activated via transphosphorylation when clustered, engages the ABL1 SH2 domain, and activates ABL1 by phosphorylation. | SIGNOR-272999 |
P40763 | P12931 | 0 | phosphorylation | up-regulates activity | 0.789 | In the present study, we have delineated the mechanism by which Galpha16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Galpha16 mutant, Galpha16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727.The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Galpha16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. | SIGNOR-247341 |
Q00535 | P08908 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.27 | Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation|5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop. | SIGNOR-264406 |
P00367 | Q9Y6E7 | 0 | glycosylation | down-regulates activity | 0.62 | We show that SIRT4 is a mitochondrial enzyme that uses NAD to ADP-ribosylate and downregulate glutamate dehydrogenase (GDH) activity. | SIGNOR-267828 |
P49810 | P29466 | 0 | cleavage | up-regulates activity | 0.32 | In decreasing order of activity, caspase-8, -3, -1, -6 and -7 proteolysed PS2 at the recognition site D326SYD329. | SIGNOR-261748 |
P07948 | Q9Y6K9 | 1 | phosphorylation | down-regulates activity | 0.357 | Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation. | SIGNOR-276369 |
Q9NQ66 | O14640 | 0 | null | up-regulates activity | 0.275 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258978 |
P42772 | Q8IXJ9 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.276 | Tumor suppressor ASXL1 is essential for the activation of INK4B expression in response to oncogene activity and anti-proliferative signals | SIGNOR-241759 |
Q9HAU4 | Q99717 | 1 | ubiquitination | down-regulates | 0.736 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-193378 |
Q13464 | O60237 | 1 | phosphorylation | down-regulates | 0.586 | Phosphorylation of ppp1r12b on threonine 646 by rho kinase inhibits the activity of the pp1c-ppp1r12b complex. | SIGNOR-198812 |
P05204 | P17252 | 0 | phosphorylation | down-regulates | 0.29 | Protein kinases that phosphorylate hmg-14 17 at the major sites have been implicated from previous in vitro studies. Protein kinase c and a similar calcium phospholipid-dependent kinase have been reported to phosphorylate both proteins in vitro, where the phosphorylation of hmg-17 occurs predominantly at ser24 and to a lesser degree at ser28. Phosphorylation of hmg-14 at ser6 by camp- or cgmp-dependent kinases has also been reported. Thus, other kinases may contribute to phosphorylation at ser6 in response to oa. Ser88 and ser98 on hmg-14 are also phosphorylated by casein kinase ii in vitro. we conclude that the correlation we observe reflects a causal relationship, in which phosphorylation somehow facilitates the redistribution of hmg-14 and -17 toward non-nuclear pools. | SIGNOR-76320 |
Q8TCG1 | Q9UNE7 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | CHIP is the ubiquitin E3 ligase mediating celastrol-triggered CIP2A degradation. | SIGNOR-272877 |
Q12852 | P45985 | 1 | phosphorylation | up-regulates activity | 0.572 | As expected, DLK significantly increased MKK4 phosphorylation on Ser257 / Thr261, and myrAKT1 enhanced MKK4 phosphorylation on Ser78 (XREF_FIG).|While MKK4 activated by DLK had strong activity in phosphorylating JNK3, MKK4 expressed with DLK and AKT1 together exhibited little activity, even though the two samples had similar levels of Ser257 / Thr261 phosphorylation (XREF_FIG). | SIGNOR-279629 |
Q8TD08 | P18031 | 0 | dephosphorylation | down-regulates | 0.326 | Erk8 (extracellular-signal-regulated protein kinase 8) expressed in escherichia coli or insect cells was catalytically active and phosphorylated at both residues of the thr-glu-tyr motif. Dephosphorylation of the threonine residue by pp2a (protein serine/threonine phosphatase 2a) decreased erk8 activity by over 95% in vitro, whereas complete dephosphorylation of the tyrosine residue by ptp1b (protein tyrosine phosphatase 1b) decreased activity by only 15-20% | SIGNOR-142981 |
P01023 | P14091 | 0 | cleavage | down-regulates quantity by destabilization | 0.38 | Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region. | SIGNOR-266977 |
Q9Y2U5 | O14733 | 1 | phosphorylation | up-regulates activity | 0.603 | MEKK2 can phosphorylate and activate MAP2K proteins MKK7 and MEK5, thereby promoting activation of JNK and ERK5, respectively [ xref ]. | SIGNOR-279212 |
P18847 | Q99988 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.426 | In addition, DIM increased the expression of NAG-1 as well as activating transcription factor 3 (ATF3), and the induction of ATF3 was earlier than that of NAG-1. The DIM treatment increased luciferase activity of NAG-1 in HCT-116 cells transfected with NAG-1 promoter construct. The results suggest that I3C represses cell proliferation through up-regulation of NAG-1 and that ATF3 may play a pivotal role in DIM-induced NAG-1 expression in human colorectal cancer cells. | SIGNOR-253725 |
P12830 | P15923 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.31 | The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation | SIGNOR-275654 |
Q9P1W9 | P30304 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.361 | The proteasome-dependent degradation of CDC25A, seen in this study upon PIM-2 over-expression, suggests that PIM-2 promotes CDC25A phosphorylation that triggers its ubiquitylation. | SIGNOR-279750 |
P12268 | P01106 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.294 | Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. | SIGNOR-267375 |
Q92835 | P07948 | 0 | phosphorylation | up-regulates activity | 0.509 | In this line, Lyn has been demonstrated to tyrosine-phosphorylate and activate SHIP1, thereby constituting a negative feedback control of PI3K-mediated signals. | SIGNOR-279060 |
P08709 | P05981 | 0 | cleavage | up-regulates activity | 0.347 | Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation|In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. I | SIGNOR-263638 |
Q9P1W9 | Q92934 | 1 | phosphorylation | down-regulates activity | 0.391 | All three Pim kinase family members predominantly phosphorylate Bad on Ser112 and in addition are capable of phosphorylating Bad on multiple sites associated with the inhibition of the pro-apoptotic function of Bad in HEK-293 cells. This would be consistent with the proposed function of Pim kinases in promoting cell proliferation and preventing cell death. | SIGNOR-249604 |
P63000 | Q38SD2 | 0 | phosphorylation | up-regulates activity | 0.292 | In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment.|Lrrk1 phosphorylates and activates RAC1 and Cdc42 small GTPase proteins in osteoclasts. | SIGNOR-279626 |
P30291 | Q93096 | 1 | phosphorylation | down-regulates activity | 0.2 | In this study , we found that WEE1 phosphorylates PRL1 and promotes PRL1 degradation .|In this study, we demonstrated that WEE1 phosphorylates and inhibits PRL1 to regulate alternative splicing of CYCD1;1 and CYCD3;1 , which may represent a new cell cycle control mechanism. | SIGNOR-278434 |
P06493 | Q969R2 | 1 | phosphorylation | up-regulates activity | 0.2 | CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes. | SIGNOR-264878 |
O96017 | P10721 | 1 | phosphorylation | up-regulates | 0.286 | In this report, we characterize the binding of sh2(chk) to specific phosphotyrosine sites on the c-kit protein sequence. the sh2(chk) binding to the two sites is direct and not through phosphorylated intermediates such as fyn or shc. this indicates that chk binds to the same site on c-kit to which fyn binds, possibly bringing the two into proximity on associated c-kit subunits and leading to the down-regulation of fyn by chk. | SIGNOR-197281 |
Q9BUZ4 | O15111 | 0 | phosphorylation | down-regulates | 0.384 | Traf4 is atypical within its family because it is the only traf family member to negatively regulate innate immune signaling. Ikk_'s phosphorylation of serine-426 on traf4 was required for this negative regulation. | SIGNOR-197253 |
P63252 | P17612 | 0 | phosphorylation | down-regulates activity | 0.2 | PKA consensus site S425 required for PKA-mediated effects on Kir2.1 channels. PKA activation reduced outward IK1 for heteromeric Kir2.1 WT+V227F channels after 2 hours of PKA activation. | SIGNOR-276267 |
P28482 | Q9HAV4 | 1 | phosphorylation | down-regulates activity | 0.301 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-262984 |
P22681 | P08581 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.732 | Tyrosine y1001, which when phosphorylated upon met activation, is involved in cbl recruitment, allowing receptor ubiquitination and down regulation | SIGNOR-185680 |
Q9HC35 | Q8TDX7 | 0 | phosphorylation | up-regulates activity | 0.274 | The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression. | SIGNOR-273884 |
O43464 | P31749 | 0 | phosphorylation | down-regulates | 0.322 | Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212 | SIGNOR-252500 |
P04626 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.601 | Ligand binding to EGFR also leads to rapid internalization and proteosomal/lysosomal degradation of the receptors. This process results in a dramatic downregulation of both total and cell surface receptors. EGF-induced degradation of EGFR is thought to be initiated by phosphorylation of tyrosine 1045 of the receptor followed by binding of Cbl adaptor proteins and ubiquitination of the receptor. Internalized EGFR is transported to early endosomes where receptor-ligand complexes are sorted for either degradation or recycling to the cell surface. | SIGNOR-30794 |
Q9Y613 | P12931 | 0 | phosphorylation | up-regulates activity | 0.306 | Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK. | SIGNOR-276612 |
P62136 | Q03112 | 1 | dephosphorylation | down-regulates activity | 0.2 | We also identified EVI1 phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein kinase II and protein phosphatase-1α. Finally, mutations that impair EVI1 phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal zinc finger domain and induced cancer cell proliferation. | SIGNOR-273430 |
Q15796 | P28482 | 0 | phosphorylation | up-regulates | 0.722 | We show that phosphorylation of smad2, a mediator of the activin/transforming growth factor-beta signal, by activated extracellular signal-regulated kinase 1 (erk1) increases the amount of smad2 protein and leads to enhanced transcriptional activity. | SIGNOR-91714 |
O43353 | Q8N2H9 | 0 | ubiquitination | up-regulates activity | 0.374 | Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination | SIGNOR-280452 |
P54252 | O95155 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.578 | Mammalian E4B (UFD2a), a ubiquitin chain assembly factor (E4), copurified with the polyubiquitylation activity for ataxin-3. E4B interacted with, and thereby mediated polyubiquitylation of, ataxin-3. Collectively, these data suggest that E4B promotes the degradation of ataxin-3, and that this effect surmounts the stabilization of ataxin-3 conferred by expansion of the polyglutamine tract. | SIGNOR-271502 |
P06400 | P67775 | 0 | dephosphorylation | up-regulates | 0.505 | This dephosphorylation returns prb to its active, growth suppressive state. | SIGNOR-75398 |
P49841 | P56524 | 1 | phosphorylation | down-regulates | 0.364 | The double mutation of serines 298/302 into alanines, but also the sole mutation of serine 302, abolishes hdac4 phosphorylation by gsk3_we have shown that cells lacking gsk3_ are unable to degrade hdac4 after serum starvation | SIGNOR-170144 |
Q9UBF6 | P67870 | 0 | phosphorylation | up-regulates activity | 0.329 | In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition. | SIGNOR-251081 |
P28482 | P19525 | 1 | phosphorylation | up-regulates | 0.2 | Our results provide strong evidence that dsrna binding is required for dimerization of full-length pkr molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eif2alpha kinase function of pkr. | SIGNOR-56337 |
P05412 | P45983 | 0 | phosphorylation | up-regulates activity | 0.907 | JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain. | SIGNOR-250122 |
Q9BV68 | P38936 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.331 | E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. | SIGNOR-272033 |
O43379 | P45985 | 1 | relocalization | up-regulates activity | 0.2 | In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis | SIGNOR-271715 |
P00533 | Q13555 | 0 | 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 |
Q9NQU5 | Q00987 | 1 | phosphorylation | up-regulates activity | 0.2 | We also showed that PAK6 phosphorylates Mdm2 on Thr-158 and Ser-186, which is critical for AR ubiquitin-mediated degradation. | SIGNOR-276428 |
O43318 | Q8IVT5 | 1 | phosphorylation | down-regulates | 0.2 | C-tak1 constitutively associates with mammalian ksr1 and phosphorylates serine 392 to confer 14-3-3 binding and cytoplasmic sequestration of ksr1 in unstimulated cells. In response to signal activation, the phosphorylation state of s392 is reduced, allowing the ksr1 complex to colocalize with activated ras and raf-1 at the plasma membrane | SIGNOR-112779 |
P53350 | Q9H1A4 | 1 | phosphorylation | up-regulates | 0.524 | Our analysis revealed an unexpected and unprecedented complexity of mitotic phosphorylation sites and suggests that other kinases than cdk1 and plk1 also contribute to apc phosphorylation. | SIGNOR-119881 |
Q8WXH4 | P04843 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.357 | We also demonstrated that ASB11 is a novel endoplasmic reticulum-associated ubiquitin ligase with the ability to interact and promote the ubiquitination of Ribophorin 1, an integral protein of the oligosaccharyltransferase (OST) glycosylation complex. Moreover, expression of ASB11 can increase Ribophorin 1 protein turnover in vivo. | SIGNOR-272057 |
P40763 | Q05655 | 0 | phosphorylation | up-regulates | 0.596 | Abrogation of pkcdelta activity inhibited insulin-induced stat3 phosphorylation, pkcdelta-stat3 association and nuclear translocation. | SIGNOR-143828 |
P48729 | Q99835 | 1 | phosphorylation | up-regulates | 0.521 | We demonstrate that mammalian Smo (mSmo) is activated through multi-site phosphorylation of its carboxyl-terminal tail by CK1α and GRK2. Phosphorylation of mSmo induces its active conformation and simultaneously promotes its ciliary accumulation. | SIGNOR-174542 |
Q96PU5 | Q9UQD0 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.325 | The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2). | SIGNOR-253461 |
Q96KS0 | O43791 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.347 | Tumor suppressor SPOP ubiquitinates and degrades EglN2 to compromise growth of prostate cancer cells | SIGNOR-261996 |
Q9HC35 | Q9HC98 | 0 | phosphorylation | up-regulates activity | 0.253 | The mitotic kinases NEK6 and NEK7 phosphorylated the EML4 N-terminal domain at Ser144 and Ser146 in vitro, and depletion of these kinases in cells led to increased EML4 binding to microtubules in mitosis. An S144A-S146A double mutant not only bound inappropriately to mitotic microtubules but also increased their stability and interfered with chromosome congression. In addition, constitutive activation of NEK6 or NEK7 reduced the association of EML4 with interphase microtubules. Together, these data support a model in which NEK6- and NEK7-dependent phosphorylation promotes the dissociation of EML4 from microtubules in mitosis in a manner that is required for efficient chromosome congression. | SIGNOR-273883 |
P11166 | P01106 | 0 | transcriptional regulation | up-regulates quantity | 0.43 | C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | SIGNOR-259987 |
Q05397 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.538 | We demonstrate here that activated Ras induces tyrosine dephosphorylation and inhibition of FAK mediated by the Ras downstream Fgd1-Cdc42-PAK1-MEK-ERK signaling cascade.| PIN1 binding and prolyl isomerization of FAK cause PTP-PEST to interact with and dephosphorylate FAK Y397. Inhibition of FAK mediated by this signal relay promotes Ras-induced cell migration, invasion, and metastasis. | SIGNOR-248661 |
O14757 | P30291 | 1 | phosphorylation | up-regulates | 0.611 | Chk1 also phosphorylates and stabilizes wee1. | SIGNOR-163164 |
P01106 | P08237 | 1 | transcriptional regulation | up-regulates quantity | 0.327 | C-Myc directly transactivates genes encoding GLUT1, phosphofructokinase, and enolase and increases glucose uptake in Rat1 fibroblasts. Nuclear run-on studies confirmed that the GLUT1 transcriptional rate is elevated by c-Myc. Our findings suggest that overexpression of the c-Myc oncoprotein deregulates glycolysis through the activation of several components of the glucose metabolic pathway. | SIGNOR-259988 |
P98177 | Q13131 | 0 | phosphorylation | up-regulates | 0.371 | The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt phosphorylation sites, resulting in foxo activation | SIGNOR-157947 |
Q92993 | P00519 | 0 | phosphorylation | down-regulates activity | 0.647 | We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65. | SIGNOR-276598 |
P60953 | O75044 | 0 | gtpase-activating protein | down-regulates activity | 0.604 | 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-260517 |
Q13177 | P05412 | 1 | phosphorylation | up-regulates | 0.268 | P21-activated protein kinase (pak2)-mediated c-jun phosphorylation at 5 threonine sites promotes cell transformationour data showed that pak2 binds and phosphorylates c-jun at five threonine sites (thr2, thr8, thr89, thr93 and thr286) | SIGNOR-170772 |
P17661 | P15172 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.24 | MyoD and HDAC2 repress myogenic late genes at early times of differentiation.A time course of Ckm, Des and Acta1 gene expression demonstrated that these genes were prematurely expressed when differentiation was driven by myogenin and Mef2D1b (Figure _(Figure6A).6A). Since MyoD is not expressed under these conditions, it cannot bind to these genes; ChIP assays demonstrated that HDAC2 also was not present on the Ckm, Des and Acta1 regulatory sequences under these conditions (Figure _(Figure6B).6B). Therefore the presence of MyoD and HDAC2 prior to gene expression functions to repress late gene expression at early times of differentiation. | SIGNOR-241762 |
P51151 | Q8IWJ2 | 1 | null | up-regulates activity | 0.54 | Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector | SIGNOR-253087 |
P07947 | P29317 | 0 | phosphorylation | up-regulates activity | 0.423 | EphA2 interacts with YES1 and phosphorylates YES1 at Tyr426 site. | SIGNOR-277556 |
O75015 | Q05481 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription. | SIGNOR-266215 |
P56945 | Q13882 | 0 | phosphorylation | up-regulates | 0.599 | Protein-tyrosine kinase 6 promotes peripheral adhesion complex formation and cell migration by phosphorylating p130 crk-associated substrate. Tyrosine residues 165 and 664 of p130cas were both phosphorylated by ptk6 in vitro | SIGNOR-177242 |
Q7Z6E9 | P67809 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.317 | RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1 | SIGNOR-271773 |
P31749 | P04049 | 1 | phosphorylation | down-regulates | 0.7 | Akt and protein kinase a (pka) phosphorylate s259 on raf-1 and inhibit its activity. | SIGNOR-147963 |
P31749 | Q07912 | 0 | phosphorylation | up-regulates activity | 0.427 | Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. | SIGNOR-252446 |
P45983 | Q07820 | 1 | phosphorylation | up-regulates | 0.526 | We found that jnk phosphorylated ser-121 and thr-163 of mcl-1 in response to stimulation with h(2)o(2) and that transfection of unphosphorylatable mcl-1 resulted in an enhanced anti-apoptotic activity in response to stimulation with h(2)o(2). Jnk-dependent phosphorylation and thus inactivation of mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage. | SIGNOR-92597 |
O43524 | Q96BR1 | 0 | phosphorylation | down-regulates activity | 0.435 | Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)|However, SGK and Akt display differences with respect to the efficacy with which they phosphorylate the three regulatory sites on FKHRL1. While both kinases can phosphorylate Thr-32, SGK displays a marked preference for Ser-315 whereas Akt favors Ser-253. These findings suggest that SGK and Akt may coordinately regulate the function of FKHRL1 by phosphorylating this transcription factor at distinct sites. The efficient phosphorylation of these three sites on FKHRL1 by SGK and Akt appears to be critical to the ability of growth factors to suppress FKHRL1-dependent transcription, thereby preventing FKHRL1 from inducing cell cycle arrest and apoptosis. | SIGNOR-249135 |
Q05513 | P35611 | 1 | phosphorylation | up-regulates | 0.2 | These data demonstrate that adducin is a significant in vivo substrate for pkc or other pma-activated kinases in a variety of cells, and that phosphorylation of adducin occurs in dendritic spines that are believed to respond to external signals by changes in morphology and reorganization of cytoskeletal structures. Ser-726 and ser-713 in the c-terminal marcks-related domains of alpha- and beta-adducin, respectively, were identified as the major phosphorylation sites common for pka and pkc. | SIGNOR-43834 |
Q16206 | Q05655 | 0 | phosphorylation | up-regulates | 0.2 | Tnox is phosphorylated by protein kinase c_ (pkc_) both in vitro and in vivo. Replacement of serine-504 with alanine significantly reduces phosphorylation by pkc_. C. overexpression of the s504a tnox mutant leads to diminished cell proliferation and migration, reflecting reduced stability of the unphosphorylatable tnox mutant protein. | SIGNOR-197706 |
Q14164 | P42224 | 1 | phosphorylation | up-regulates | 0.4 | 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-154775 |
P20645 | Q7Z6M1 | 0 | relocalization | up-regulates activity | 0.385 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253091 |
Q8IXL6 | Q2M3R5 | 1 | phosphorylation | up-regulates activity | 0.2 | Notably, phosphorylation of Stim1 by Fam20C enhances Stim1 activation and store-operated Ca 2+ entry.|We feel that the western blot shows an appropriate range of contrast to support the conclusion that Stim1 can be activated by Fam20C under high calcium conditions. | SIGNOR-280012 |
P42229 | Q9Y6K1 | 1 | transcriptional regulation | up-regulates quantity | 0.326 | … these data suggest that STAT5A positively regulates levels of DNMT3A, resulting in inactivation of tumor suppressor genes by epigenetic mechanisms in AML cells | SIGNOR-255631 |
P67775 | Q9UIC8 | 0 | methylation | up-regulates activity | 0.908 | Methylation of the carboxy-terminal Leu309 in a conserved TPDYFL309 motif of the C subunit has been shown to enhance the affinity of the PP2A core enzyme for some, but not all, regulatory subunits |The PP2A core enzyme was methylated by a PP2A-specific leucine carboxyl methyltransferase (LCMT1) | SIGNOR-265749 |
Q02750 | P10398 | 0 | phosphorylation | up-regulates | 0.74 | Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling|The immunoprecipitates were assayed for GST-MEK1 activation. D, activation of MEK1 by A-Raf requires the presence of serine residue 218 and 222. | SIGNOR-235944 |
P05362 | Q86YJ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | MARCH-IX expression causes ubiquitination and downregulation of ICAM-1 and a short alternative transcript of MARCH-IX lacking the RING-CH domain, termed MARCH-IX RINGless, is shown to act as a positive regulator of MARCH-IX activity.|MARCH-IX mediates ubiquitination and downregulation of ICAM-1. | SIGNOR-278821 |
P18031 | P49841 | 0 | phosphorylation | down-regulates quantity | 0.469 | GSK-3beta phosphorylates PTP1B at serine residues, and activation of GSK-3beta reduces the mRNA level of PTP1B. | SIGNOR-279724 |
Q86TM6 | P10909 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.32 | We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The fact that cleaved endogenous clusterin appears, under certain conditions, to be subject to polyubiquitination (Figure 2C) and proteasomal degradation (1, 2) strongly suggests that it passed through the secretory pathway before reaching the cytosol. | SIGNOR-272629 |
P55010 | P67870 | 0 | phosphorylation | up-regulates activity | 0.379 | Mass spectrometric analysis of maximally in vitro phosphorylated eIF5 localized the major phosphorylation sites at Ser-387 and Ser-388 near the C-terminus of eIF5. These serine residues are embedded within a cluster of acidic amino acid residues and account for nearly 90% of the total in vitro eIF5 phosphorylation. A minor phosphorylation site at Ser-174 was also observed. | The results suggest that phosphorylation of eIF5 may have a role in stimulating the rate of eIF5-promoted GTP hydrolysis. | SIGNOR-251070 |
P12931 | P35228 | 1 | phosphorylation | up-regulates | 0.681 | We identify human inos residue tyr(1055) as a target for src-mediated phosphorylation. src kinase-mediated phosphorylation stabilizes inducible nitric-oxide synthase in normal cells and cancer cells. | SIGNOR-188974 |
P30622 | P06493 | 0 | phosphorylation | up-regulates activity | 0.49 | Cdc2 phosphorylates T287|CLIP-170, the founding member of microtubule “plus ends tracking” proteins, is involved in many critical microtubule-related functions, including recruitment of dynactin to the microtubule plus ends and formation of kinetochore-microtubule attachments during metaphase. |These results demonstrate that Cdc2-mediated phosphorylation of CLIP-170 is essential for the normal function of this protein during cell cycle progression. | SIGNOR-275470 |
P84085 | O43150 | 0 | gtpase-activating protein | up-regulates activity | 0.497 | Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Pap protein exhibits Arf GAP activity in vitro. | SIGNOR-269707 |
Q00987 | P67775 | 0 | dephosphorylation | up-regulates activity | 0.455 | cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells | SIGNOR-248636 |
P06850 | Q92731 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.386 | Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.|Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. | SIGNOR-268722 |
P49841 | P48436 | 1 | phosphorylation | down-regulates activity | 0.444 | (E) The SOX9 K2 domain is phosphorylated by GSK3\u03b2 at T236.|Based on our findings that inhibition of GSK3\u03b2 prevents DNA damage-induced SOX9 degradation, and that FBW7 targets SOX9 for degradation after DNA damage, we reasoned that phosphorylation of SOX9 by GSK3\u03b2 is required for FBW7-mediated SOX9 degradation. | SIGNOR-279725 |
Q9Y3S1 | Q9H4A3 | 1 | phosphorylation | up-regulates activity | 0.546 | WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro. | SIGNOR-260790 |
P25685 | Q8IW41 | 0 | phosphorylation | up-regulates | 0.463 | Phosphorylation of heat shock protein 40 (hsp40/dnajb1) by mitogen-activated protein kinase-activated protein kinase 5 (mk5/prak). Mk5 phosphorylates hsp40/dnajb1 in vivo at ser-149 or/and ser-151 and ser-171 in the c-terminal domain of hsp40/dnajb1. Mk5 modestly stimulates the atp hydrolyse activity of hsp40/hsp70 complex and enhances the repression of heat shock factor 1 driven transcription by hsp40/dnajb1. | SIGNOR-203464 |
Q92934 | P31751 | 0 | phosphorylation | down-regulates | 0.525 | Ser-136 is the major phosphoacceptor site for akt;akt can weakly phosphorilate ser-155. | SIGNOR-81114 |
Q9UPT6 | Q13464 | 0 | phosphorylation | up-regulates | 0.332 | Identification of rock1 as an upstream activator of the jip-3 to jnk signaling axis in response to uvb damage. phosphorylation of jip-3 by rock1 was crucial for the recruitment of jnk. Inhibition of the activity of rock1 in keratinocytes resulted in decreased activation of the jnk pathway and thus a reduction in apoptosis. | SIGNOR-134588 |
P53350 | O15350 | 1 | phosphorylation | down-regulates | 0.51 | P73-mediated transcriptional activity is negatively regulated by polo-like kinase 1. tap73 is phosphorylated by this kinase on threonine-27 (thr-27) within the ta domain. | SIGNOR-178253 |
P51530 | O96017 | 0 | phosphorylation | up-regulates activity | 0.526 | We later observed that Dna2 phosphorylation by Cds1 is necessary for Dna2 association with chromatin in HU treated cells. | SIGNOR-279729 |
O14713 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.307 | The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited. | SIGNOR-250632 |
Q9H9S0 | Q9UGL1 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.308 | Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes. | SIGNOR-273451 |
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