IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
Q14194 | Q00535 | 0 | phosphorylation | up-regulates | 0.622 | These findings suggest that sema3a-induced spine development is regulated by phosphorylation of crmp1 by cdk5. Introduction of crmp1-wt, but not crmp1-t509a/s522a, a crmp1 mutant that cannot be phosphorylated by cdk5, rescued the defect in sema3a responsiveness. | SIGNOR-159314 |
P48740 | Q9BWP8 | 0 | binding | up-regulates activity | 0.622 | On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms. | SIGNOR-263409 |
P06213 | P17706 | 0 | dephosphorylation | down-regulates | 0.622 | Finally, we have tested the set of ptps for their ability to dephosphorylate a phosphopeptide corresponding to the irk autophosphorylation site. tc-ptp, sap-1, and ptp-1b all tested positive, but ptp-? Showed no activity, although the same gst-ptp preparation could efficiently convert pnpp (tablei). Interestingly, many other ptps showed activity, namely dep-1, glepp-1, lar, ptp-?, -?, -?, And shp-1. | SIGNOR-75914 |
O75122 | P53350 | 0 | phosphorylation | up-regulates activity | 0.622 | Cdk1 and Plk1 mediate a CLASP2 phospho-switch that stabilizes kinetochore-microtubule attachments.|Finally, we demonstrate that CLASP2 phosphorylation on S1234 and S1255 by Cdk1 and Plk1, respectively, increases with conditions that allow the establishment and stabilization of KT\u2013MT attachments ( xref ). | SIGNOR-278321 |
P84022 | P31749 | 0 | binding | down-regulates | 0.622 | Pkb inhibits smad3 by preventing its phosphorylation, binding to smad4 and nuclear translocation. [...] Regulation of smad3 by pkb occurs through a kinase-activity-independent mechanism, resulting in a decrease in smad3-mediated transcription and protection of cells against tgf-beta-induced apoptosis. | SIGNOR-123606 |
Q9UH99 | P02545 | 0 | relocalization | up-regulates activity | 0.622 | In the case of Sun2, there is some evidence that A-type lamins might contribute to Sun2 localization in the INM. We report that an interaction between subunits of the HOPS complex and the ERM (ezrin, radixin, moesin) proteins is required for the delivery of EGF receptor (EGFR) to lysosomes. Inhibiting either ERM proteins or the HOPS complex leads to the accumulation of the EGFR into early endosomes, delaying its degradation. | SIGNOR-261310 |
P40763 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.622 | 29 PTK6 promotes activating phosphorylation of STAT3 at tyrosine residue 705.|STAT3 has been shown to promote tumor initiation of different tumor types, including those of the gastrointestinal tract and skin, and PTK6 was previously shown to promote STAT3 activation and tumorigenesis in mouse models of colon and skin cancer. | SIGNOR-278346 |
P63000 | Q86VW2 | 0 | guanine nucleotide exchange factor | up-regulates | 0.622 | Exogenous expression of geft promotes myogenesis ofc2c12 cells via activation of rhoa, rac1, and cdc42 and their downstream effector proteins, while a dominant negative mutant of geft inhibits this process. | SIGNOR-236882 |
P62136 | Q12972 | 0 | binding | down-regulates activity | 0.622 | We have purified two of these nuclear inhibitors of PP-1 (NIPP-1a and NIPP-1b) until homogeneity. | SIGNOR-255657 |
P14210 | P40763 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.622 | Coexpression of activated c-Src and Stat3 synergistically induced strong HGF promoter activity in SP1 cells | SIGNOR-251742 |
Q9NPG1 | O14904 | 0 | binding | up-regulates | 0.622 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132070 |
P43268 | Q15831 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.622 | LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. | SIGNOR-279293 |
P21802 | Q06124 | 0 | dephosphorylation | down-regulates activity | 0.622 | In forming this heterotetrameric complex Grb2 inhibits both the dephosphorylation of FGFR2 by Shp2 and the phosphorylation of Shp2 by FGFR2 (XREF_FIG, respectively).|Knockdown of Grb2 elevates Shp2 phosphorylation (XREF_FIG), strongly suggesting that the inability of Shp2 to interact directly with the receptor in the presence of Grb2 prevents FGFR2 kinase activity toward Shp2. | SIGNOR-277030 |
P08151 | Q2M1P5 | 0 | binding | up-regulates quantity by stabilization | 0.622 | Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling. | SIGNOR-209608 |
P28482 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.621 | P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).Mapk activity is tightly regulated by phosphorylation and dephosphorylation. The activation of the mapk activity requires the dual phosphorylation of the ser/thr and tyr residues in the txy kinase activation motif (1113), and deactivation occurs through the action of either ser/thr protein phosphatase | SIGNOR-103159 |
P31751 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.621 | The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells. | SIGNOR-248328 |
Q92831 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.621 | Consistently, overexpression of MDM2 in p53 null cells caused the reduction of the protein level of PCAF, but not the mRNA level.|MDM2 ubiquitinated PCAF in vitro and in cells. | SIGNOR-278825 |
P06213 | O14492 | 0 | binding | down-regulates | 0.621 | APS couples c-Cbl to the insulin receptor, resulting in ubiquitination of the insulin receptor. | SIGNOR-109694 |
O14640 | Q53G59 | 0 | binding | down-regulates quantity by destabilization | 0.621 | KLHL12 recruits Dsh to Cullin-3 for protein degradation. In vitro ubiquitination of Dsh3 by KLHL12–Cullin-3–Roc1. The E3 ligase complex was obtained by transfection of HEK293T cells . We show that the BTB-containing protein KLHL12 negatively regulates Dsh function by recruiting a pool of Dsh to the Cullin-3 ligase scaffold, thereby promoting its ubiquitination and degradation. | SIGNOR-271558 |
P40763 | Q16539 | 0 | 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 |
O95644 | P45983 | 0 | phosphorylation | down-regulates activity | 0.621 | It has been previously shown that NF-ATc1 accumulates in the nucleus of activated CD4 + T cells from Jnk1 \n \u2212/\u2212 mice 35\u2022 and that JNK1 phosphorylates and inactivates NFATc1 in Jurkat T cells 47 , indicating that JNK1 is an inhibitor of NFAT. | SIGNOR-280031 |
P63092 | P13945 | 0 | binding | up-regulates activity | 0.621 | Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. | SIGNOR-256753 |
P49841 | O14640 | 0 | binding | down-regulates activity | 0.621 | In canonical wnt signaling, dsh phosphorylation inhibits the apcaxingsk3 complex, leading to beta-catenin stabilization. | SIGNOR-167957 |
O75376 | Q96EB6 | 0 | null | up-regulates | 0.621 | In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription. | SIGNOR-253505 |
P15172 | Q96EB6 | 0 | null | down-regulates activity | 0.621 | Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle differentiation | SIGNOR-241963 |
Q9NPG1 | Q9H1J5 | 0 | binding | up-regulates | 0.621 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131984 |
P10070 | Q6PHR2 | 0 | phosphorylation | up-regulates activity | 0.621 | We show that ULK3 is able to phosphorylate three mammalian GLI proteins in vitro | SIGNOR-260798 |
P05114 | O75582 | 0 | phosphorylation | down-regulates activity | 0.62 | HMGN1 (formerly known as HMG-14) phosphorylation at Ser6 occurs concomitantly with IE gene expression. | MSK2 seems to be the most important kinase responsible for this modification |Accordingly, it was suggested that HMGN1 phosphorylation reduces binding of the protein to the nucleosomes | SIGNOR-262988 |
P57764 | P51878 | 0 | cleavage | up-regulates activity | 0.62 | Co-expression of GSDMD with caspase-1, 4, 5 or 11 but not apoptotic caspases (caspase-2, 8 and 9) in 293T cells induced the same cleavage of GSDMD|inflammatory caspases specifically cleave GSDMD after the 272FLTD275 (or 273LLSD276) sequence | | SIGNOR-256418 |
O14746 | Q9NPE3 | 0 | binding | up-regulates activity | 0.62 | Dyskerin was recently found to be associated with active human telomerase (34), and mutations in dyskerin or NOP10 or deletion of the H/ACA motif of hTERC result in diminished telomerase activity | SIGNOR-263331 |
P56524 | Q16566 | 0 | phosphorylation | down-regulates activity | 0.62 | CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus. | SIGNOR-250712 |
Q92673 | P02649 | 0 | binding | up-regulates | 0.62 | Lr11 binds the apolipoprotein e (apoe)-rich lipoproteins, beta-very low density lipoproteins (vldls), with a high affinity similar to that of other members, such as the ldlr and vldl receptor.Incubation For 48 hours with beta-vldl of lr11-overexpressing cells, but not of control cells, promotes the appearance of numerous intracellular lipid droplets. | SIGNOR-110555 |
Q13547 | P68400 | 0 | phosphorylation | up-regulates | 0.62 | Human hdac1 protein was analyzed by ion trap mass spectrometry, and two phosphorylated serine residues, ser(421) and ser(423), were unambiguously identified. Loss of phosphorylation at ser(421) and ser(423) due to mutation to alanine or disruption of the casein kinase 2 consensus sequence directing phosphorylation reduced the enzymatic activity and complex formation of hdac1. | SIGNOR-111015 |
Q07352 | P49137 | 0 | phosphorylation | down-regulates | 0.62 | Mk2-mediated inhibition of brf1 requires phosphorylation at s54, s92, and s203. Phosphorylation of brf1 by mk2 does not appear to alter its ability to interact with ares or to associate with mrna decay enzymes. Thus, mk2 inhibits brf1-dependent amd through direct phosphorylation. | SIGNOR-161274 |
O00470 | P31269 | 0 | binding | up-regulates activity | 0.62 | We now show that the Hoxa-9 protein physically interacts with Meis1 proteins. Hox proteins from the other AbdB-like paralogs, Hoxa-10, Hoxa-11, Hoxd-12, and Hoxb-13, also form DNA binding complexes with Meis1b. DNA binding complexes formed by Meis1 with Hox proteins dissociate much more slowly than DNA complexes with Meis1 alone, suggesting that Hox proteins stabilize the interactions of Meis1 proteins with their DNA targets. | SIGNOR-241162 |
P25092 | Q16661 | 0 | binding | up-regulates | 0.62 | Guanylins activate two receptors, gc-c and ok-gc, which are expressed in intestine and/or kidney. | SIGNOR-78120 |
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 |
Q16566 | Q8N5S9 | 0 | phosphorylation | up-regulates | 0.62 | Phosphorylation of ca(2+)/cam-bound camkiv on its activation loop threonine (residue thr(200) in human camkiv) by ca(2+)/calmodulin-dependent kinase kinase leads to increased camkiv kinase activity. | SIGNOR-134649 |
O95835 | Q13188 | 0 | phosphorylation | up-regulates | 0.62 | Since the N-terminal half of Lats1 (residues 1588) was dispensable for the activation of Lats1 by Mst2, mass spectrometry was used to identify phosphorylation sites within the C-terminal domain of Lats1. | SIGNOR-132927 |
Q16566 | Q96RR4 | 0 | phosphorylation | up-regulates activity | 0.62 | Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation. | SIGNOR-250718 |
P16885 | P07948 | 0 | phosphorylation | up-regulates activity | 0.62 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-249384 |
Q04864 | O14920 | 0 | phosphorylation | up-regulates activity | 0.62 | We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta. | SIGNOR-279620 |
P37231 | P18146 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.62 | Previous studies have reported that the PPARγ proximal promoter contains an overlapping binding site for Egr-1, which is involved in the down-regulation of PPARγ. In the present study, we have provided direct evidence that leptin causes PPARγ reduction in primary cultured PASMC; this effect is coupled to leptin-induced ERK1/2 activation and subsequent induction of Egr-1, which further down-regulates PPARγ expression and results in PASMC proliferation. The present study confirmed that ERK1/2 signaling cascade mediated leptin-induced PPARγ reduction by up-regulation of Egr-1 in PASMC. | SIGNOR-263508 |
P11142 | Q9HAV7 | 0 | binding | down-regulates activity | 0.62 | As we had observed earlier,HMGE bound avidly to DnaK (Fig. 5A). In addition, bothMt-Hsp70 and Hsc70 bound to GST-HMGE, but Hsc70 appeared to bind with lower affinity. HMGE inhibitedthe co-chaperone enhancement of Hsc70 ATPase activity byapproximately 50% (Table 1). | SIGNOR-261241 |
Q9Y6H5 | O43255 | 0 | ubiquitination | down-regulates | 0.62 | Siah proteins ubiquitylate synphilin-1 and promote its degradation through the ubiquitin proteasome system | SIGNOR-140651 |
P61586 | O15068 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.619 | 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-260559 |
Q8NHV4 | P53350 | 0 | phosphorylation | up-regulates activity | 0.619 | Here we report that the function of Nedd1 is regulated by Cdk1 and Plk1. During mitosis, Nedd1 is firstly phosphorylated at T550 by Cdk1, which creates a binding site for the polo-box domain of Plk1. Then, Nedd1 is further phosphorylated by Plk1 at four sites: T382, S397, S637 and S426. The sequential phosphorylation of Nedd1 by Cdk1 and Plk1 promotes its interaction with gamma-tubulin for targeting the gammaTuRC to the centrosome and is important for spindle formation. | SIGNOR-272992 |
Q92769 | P68400 | 0 | phosphorylation | up-regulates | 0.619 | Protein kinase ck2-mediated phosphorylation of hdac2 regulates co-repressor formation, deacetylase activity and acetylation of hdac2 by cigarette smoke and aldehydesstudies using unfractionated cell extracts with ck2 inhibitors suggest that protein kinase ck2 is the major source of hdac2 kinase. Finally, and perhaps most interesting, hdac2 phosphorylation promotes enzymatic activity, selectively regulates complex formation, but has no effect on transcriptional repression. Together, our data indicate that like many hdacs, hdac2 is regulated by post-translational modification, particularly phosphorylation. | SIGNOR-164795 |
P00533 | Q6UW88 | 0 | binding | up-regulates | 0.619 | Remarkably, three members of the epidermal growth factor (egf) family (ereg, areg, and epgn) showed increased expression that was associated with elevated epidermal activation of the egf receptor (egfr) and stat3, a downstream effector of egfr signaling. | SIGNOR-165779 |
P55212 | P42574 | 0 | cleavage | up-regulates | 0.619 | Caspase-3 is required for the activation of caspases 6 | SIGNOR-64179 |
P43403 | P06239 | 0 | phosphorylation | up-regulates activity | 0.619 | We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56lck | SIGNOR-249375 |
Q96SD1 | Q13315 | 0 | phosphorylation | up-regulates | 0.619 | The artemis nuclease is defective in radiosensitive severe combined immunodeficiency patients and is required for the repair of a subset of ionising radiation induced dna double-strand breaks (dsbs) in an atm and dna-pk dependent process. Here, we show that artemis phosphorylation by atm and dna-pk in vitro is primarily attributable to s503, s516 and s645 and demonstrate atm dependent phosphorylation at serine 645 in vivo | SIGNOR-148315 |
P31749 | Q96RU7 | 0 | binding | down-regulates activity | 0.619 | TRB3 expression is induced in liver under fasting conditions, and TRB3 disrupts insulin signaling by binding directly to Akt and blocking activation of the kinase. | SIGNOR-252644 |
P60953 | Q96M96 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.619 | 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-260554 |
P54646 | Q96RR4 | 0 | phosphorylation | up-regulates | 0.619 | These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo. | SIGNOR-138364 |
Q8IW41 | Q15759 | 0 | phosphorylation | up-regulates | 0.619 | Prak activity was regulated by p38alpha and p38beta both in vitro and in vivo and thr182 was shown to be the regulatory phosphorylation site. | SIGNOR-58131 |
P04626 | Q05209 | 0 | dephosphorylation | down-regulates activity | 0.619 | In MDA-MB-231 cells, a human triple negative breast cancer cell line, phosphorylation of PTPN12 on Ser 19 was increased in response to cyclin dependent kinase 2 (CDK2), and this impaired PTPN12 's ability to dephosphorylate HER2 on Y1196.|PTPN12 negatively regulates Her2, by dephosphorylation on Tyr 1196 on Her2. | SIGNOR-277038 |
P19174 | Q16288 | 0 | binding | up-regulates | 0.619 | Unglycosylated trka core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules shc and plc-gamma. | SIGNOR-67404 |
Q92547 | O60671 | 0 | binding | up-regulates | 0.619 | The 9-1-1 complex functions as a clamp, encircling the dna, and recruits the brct domain-containing protein topbp1 in a phospho-dependent manner | SIGNOR-179379 |
Q13467 | O00744 | 0 | binding | up-regulates | 0.619 | Inhibition of adipogenesis by wnt10b is likely mediated by‚ wnt‚ receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 8 | SIGNOR-210164 |
P25089 | P04083 | 0 | binding | up-regulates activity | 0.618 | We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2. | SIGNOR-259438 |
P23258 | Q14980 | 0 | binding | up-regulates | 0.618 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117203 |
P40763 | P08631 | 0 | phosphorylation | up-regulates activity | 0.618 | Activation of STAT3 by the Src family kinase Hck requires a functional SH3 domain. Direct Phosphorylation of STAT3 on Tyr-705 by Src Family Kinases | SIGNOR-251267 |
O75460 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.618 | ASK1 may directly phosphorylate IRE1\u03b1 at sites other than the IRE1\u03b1 autophosphorylation site. | SIGNOR-279213 |
P98170 | P31749 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.618 | Akt, including akt1 and akt2, interacts with and phosphorylates x-linked inhibitor of apoptosis protein (xiap) at residue serine-87 in vitro and in vivo. Phosphorylation of xiap by akt protects xiap from ubiquitination and degradation in response to cisplatin. | SIGNOR-119488 |
O75581 | O14905 | 0 | binding | up-regulates | 0.618 | We find that wnt9b binds to a different part of the lrp6 extracellular domain | SIGNOR-163552 |
O75582 | P28482 | 0 | phosphorylation | up-regulates | 0.617 | Together, our in vivo and in vitro studies indicate that the pkc/c-raf/mek/erk pathway plays a major role in the s6k1 activation in hypertrophic cardiac growth. | SIGNOR-131311 |
P15056 | Q6VAB6 | 0 | binding | up-regulates activity | 0.617 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273877 |
Q99708 | P24941 | 0 | phosphorylation | up-regulates | 0.617 | Collectively, these findings thereby provided strong support for ctip thr-847 indeed being a cdk target. it is established that both cdk-dependent and checkpoint-dependent phosphorylations are required for activation of sae2/ctip in vivo | SIGNOR-183840 |
P08047 | P23511 | 0 | binding | up-regulates activity | 0.617 | Our results further confirm the important transactivating role for NF-Y for the CBS-1b promoter, via its synergism with Sp1. While differential phosphorylation of Sp1 likely contributes to binding to multiple GC-/GT-boxes in the CBS-1b and promoter activation [16], NF-Y is clearly necessary for a maximal activation response. | SIGNOR-254816 |
P21912 | Q9NX18 | 0 | binding | up-regulates | 0.617 | Sdh5 is required for sdh activity and stability / the sdh1-sdh5 interaction is likely to be functionally important because the sdh5_ mutant lacks sdh activity | SIGNOR-187239 |
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 |
Q9NT99 | P10586 | 0 | binding | up-regulates activity | 0.617 | The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. | SIGNOR-264049 |
Q92783 | O60674 | 0 | phosphorylation | up-regulates | 0.617 | Stam is associated with jak3 and jak2 tyrosine kinases via its itam region and phosphorylated by jak3 and jak2 upon stimulation with il-2. | SIGNOR-47834 |
Q9NPG1 | Q9UBV4 | 0 | binding | up-regulates | 0.617 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131674 |
O75581 | Q93098 | 0 | binding | up-regulates | 0.617 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132027 |
P04049 | O60674 | 0 | phosphorylation | up-regulates activity | 0.617 | JAK2 phosphorylated Raf-1. e sites at 340/341 are indeed phosphorylated by JAK2 and that this phosphorylation represents a major component of the activation process. | SIGNOR-251361 |
Q9NPG1 | O00744 | 0 | binding | up-regulates | 0.617 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-131625 |
Q9UQC2 | P27361 | 0 | phosphorylation | up-regulates | 0.617 | Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623. | SIGNOR-128731 |
Q13043 | P42574 | 0 | cleavage | up-regulates activity | 0.617 | In response to apoptotic stimuli, caspase cleavage of mst1 occurs at asp-326 and asp-349, resulting in the separation of its n-terminal kinase domain from the nes-containing c-terminal domain. Thus, caspase cleavage of mst1 serves two purposes: one is activation of mst1 kinase activity and the other is translocation of mst1 into the nucleus. | SIGNOR-109878 |
P61586 | Q12774 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.617 | 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-260533 |
Q92529 | P00533 | 0 | binding | up-regulates | 0.617 | Several tyrosine-based motifs recruit a number of signal transducers to the phosphorylated form of erbb1 such as the adaptor proteins growth-factor-receptor bound-2 (grb2) and src-homology-2-containing (shc). | SIGNOR-55861 |
P53667 | Q13464 | 0 | phosphorylation | up-regulates activity | 0.617 | Rho-associated kinase rock activates lim-kinase 1 by phosphorylation at threonine 508 within the activation loop. | SIGNOR-74569 |
Q13547 | P37231 | 0 | relocalization | down-regulates | 0.617 | These data suggest that c/ebp beta activates a single unified pathway of adipogenesis involving its stimulation of ppargamma expression, which then activates c/ebp alpha expression by dislodging hdac1 from the promoter for degradation in the proteasome | SIGNOR-143961 |
Q9NZJ5 | Q13217 | 0 | binding | down-regulates activity | 0.616 | The protein p58IPK {also known asDnaJ3C [DnaJ heat-shock protein (hsp) 40 homologue, subfamily C, member 3]} is known to inhibit the eIF2 kinases PKR (dsRNA-dependent protein kinase/eIF2 kinase 2) and PERK | SIGNOR-246201 |
P29353 | P29317 | 0 | binding | up-regulates | 0.616 | We also show that the interaction of epha2 with grb2 is indirect and mediated by shc and that this complex is necessary for epha2-mediated activation of erk kinases. | SIGNOR-94804 |
P20336 | P17600 | 0 | binding | up-regulates activity | 0.616 | Synapsins, a family of neuron-specific phosphoproteins, have been demonstrated to regulate the availability of synaptic vesicles for exocytosis by binding to both synaptic vesicles and the actin cytoskeleton in a phosphorylation-dependent manner. The interaction between synapsin I and Rab3A was confirmed by photoaffinity labeling experiments on purified synaptic vesicles and by the formation of a chemically cross-linked complex between synapsin I and Rab3A in intact nerve terminals. The data indicate that synapsin I is a novel Rab3 interactor on synaptic vesicles and suggest that the synapsin-Rab3 interaction may participate in the regulation of synaptic vesicle trafficking within the nerve terminals. | SIGNOR-269181 |
Q07955 | P78362 | 0 | phosphorylation | up-regulates activity | 0.616 | In contrast, SRPK1 or SRPK2 overexpression upregulated the phosphorylation and nucleus accumulation of SRSF1.|Therefore, SRPK1 and SRPK2 may directly phosphorylate SRSF1 and promote it nucleus translocation, subsequently modulate MKNK2 alternative splicing. | SIGNOR-279660 |
P15172 | Q92793 | 0 | acetylation | up-regulates | 0.616 | Our results provide direct evidence that myod acetylation functionally activates the protein and show that both pcaf and cbp/p300 are candidate enzymes for myod acetylation in vivo. | SIGNOR-81050 |
O75582 | Q15759 | 0 | phosphorylation | up-regulates | 0.615 | Mitogen- and stress-activated protein kinase-1 (msk1) is directly activated by mapk and sapk2/p38, and may mediate activation of crebactivated by phosphorylation at ser-360, thr-581 and thr-700 by mapk1/erk2, mapk3/erk1 and mapk14/p38-alpha | SIGNOR-59443 |
P04626 | P12931 | 0 | phosphorylation | up-regulates activity | 0.615 | In addition, the c-Src inhibitor 4-(4\u2019-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2.|On the other hand, c-Src directly phosphorylates the cytoplasmic tails of both EGFR and HER2, allowing the binding of scaffold proteins that will further activate signal transduction. | SIGNOR-279432 |
Q99650 | Q6EBC2 | 0 | binding | up-regulates | 0.615 | Here we identify a four-helix bundle cytokine we have called interleukin 31 (il-31), which is preferentially produced by t helper type 2 cells. Il-31 signals through a receptor composed of il-31 receptor a and oncostatin m receptor. | SIGNOR-125347 |
Q01196 | Q00534 | 0 | phosphorylation | up-regulates | 0.615 | We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein. | SIGNOR-138953 |
P42224 | P40763 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.615 | In summary, we report in this study that STAT1 expression is upregulated by nuclear EGFR, EGFRvIII and HER2, and that STAT3 synergizes with the three receptors to further enhance STAT1 expression. These novel findings establish a novel link between the mitogenic ErbB signaling pathway and the inflammatory pathway mediated by STAT1. The oncogenic transcription factor STAT3 binds to the STAT1 promoter and synergizes with nuclear EGFR to significantly enhance STAT1 gene expression. | SIGNOR-263650 |
P18846 | O75676 | 0 | phosphorylation | up-regulates | 0.615 | Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1. | SIGNOR-116252 |
P00742 | P38435 | 0 | carboxylation | up-regulates activity | 0.615 | This report describes the expression, purification, and characterization of a series of recombinant factor Xa variants bearing aspartate substitutions for each of the glutamate residues which normally undergo gamma-carboxylation. |We have produced fully active recombinant human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical for normal activity of factor Xa.|This observation suggests that, for wild-type r-fX expressed in HEK cells, carboxylation by the gamma-glutamyl carboxylase proceeds to completion once initiated; | 11 amino terminal glutamic acid residues of fX which normally undergo gamma-carboxylation (glas 6, 7, 14, 16, 19, 20, 25, 26, 29, 32, 39). | SIGNOR-263667 |
O43639 | P09619 | 0 | binding | up-regulates | 0.615 | The sh2 domains of grb2, nck, and grb4 all precipitated activated pdgf receptor with similar efficiency. | SIGNOR-64740 |
O95622 | P38405 | 0 | binding | up-regulates activity | 0.615 | D1-class dopamine receptors (D1 and D5) activate the G s/olf family of G proteins to stimulate cAMP produc tion by AC and are found exclusively postsynaptically on dopamine-receptive cells, such as GABA-ergic medium spiny neurons (MSNs) in the striatum. | SIGNOR-264997 |
Q02750 | Q9UHA4 | 0 | binding | up-regulates | 0.615 | We analyzed the ability of mp1 to bind to mek1, erk1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major mp1 peaks: a broad high molecular weight peak and a 28 kda complex. An mp1 mutant that lost mek1 binding no longer enhanced rasv12-stimulated erk1 activity, and functioned as a dominant negative, consistent with the concept that mp1 function depends on facilitating these oligomerizations. | SIGNOR-130924 |
Q99708 | Q13535 | 0 | phosphorylation | up-regulates | 0.615 | Characterization of this site using phospho-specific antibodies and mutational analysis reveals that it is phosphorylated by atr and is required for binding of ctip to chromatin and subsequent processive resection. | SIGNOR-200245 |
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