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 |
|---|---|---|---|---|---|---|---|
P00533 | O15126 | 1 | phosphorylation | up-regulates activity | 0.335 | In our efforts to identify cellular tyrosine kinases that phosphorylate SCAMPs, we are quite intrigued by the observation that among a number of kinases, only the EGFR exhibits activity toward SCAMPs. EGF catalyzes the progressive phosphorylation of the SCAMPs up to 1 h poststimulation and may enhance colocalization of the EGFR and SCAMP3 within the cell interior. EGF also induces SCAMP-EGFR association, as detected by coimmunoprecipitation, and phosphorylation of SCAMP3 is stimulated by the EGFR in vitro. These results suggest that phosphorylation of SCAMPs, either directly or indirectly, may be functionally linked to the internalization/down-regulation of the EGFR. we have observed that there are two tyrosines conserved in SCAMP1 and SCAMP3, which are not found in SCAMP2. Of these two tyrosines (Tyr37 and Tyr73 in SCAMP1; Tyr 41 and Tyr83 in SCAMP3), we consider Tyr37/41 to be a more likely site for tyrosine phosphorylation | SIGNOR-262857 |
P60228 | P33993 | 1 | binding | up-regulates quantity by stabilization | 0.335 | Our data show that INT6 interacts with a C-terminal domain of MCM7. Collectively, our observations suggest that INT6 restrains the increased degradation of MCM7 occurring during DNA replication by protecting its polyubiquitylated derivatives from the proteasome activity. | SIGNOR-259154 |
P27361 | Q9UQ13 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.335 | Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. | SIGNOR-277443 |
P22674 | P06493 | 1 | binding | up-regulates activity | 0.335 | CDK2 is the predominant activating complex form of CCNO, but CCNO can bind to CDK1 to form an activating complex in the absence of CDK2. | SIGNOR-275617 |
P53350 | Q9H2D6 | 1 | phosphorylation | up-regulates | 0.335 | Here we show that tara is a novel polo-like kinase 1 (plk1) target protein. Plk1 interacts with and phosphorylates tara in vivo and in vitro. Actually, the thr-457 in tara was a bona fide in vivo phosphorylation site for plk1. Interestingly, we found that the centrosomal localization of tara depended on the thr-457 phosphorylation and the kinase activity of plk1 | SIGNOR-198353 |
P28482 | Q12800 | 1 | phosphorylation | down-regulates | 0.335 | We previously established that phosphorylation of lsf in early g1 at ser-291 and ser-309 inhibits its transcriptional activity and that dephosphorylation later in g1 is required for its reactivation. At the peak activities of erk and cyclin c/cdk2 in early g1, lsf is efficiently phosphorylated on ser-291 and ser-309. | SIGNOR-184168 |
P12931 | O75955 | 1 | phosphorylation | up-regulates activity | 0.335 | Taken together, we conclude that mitochondrial c-Src phosphorylates flotillin-1 at Tyr56 and Tyr149, and that these phosphorylations are required for its interaction with CxII and the prevention of ROS production. | SIGNOR-273805 |
P50613 | P21127 | 1 | phosphorylation | up-regulates activity | 0.335 | We conclude that CDK7 phsphorylates Cdk11, dependent on the conserved Thr219 residue in the CDK11 T loop, and it is therefore likely to be a genuine Cdk11 activating kinase | SIGNOR-245871 |
Q5T0F9 | P08908 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.335 | Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression|Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells. | SIGNOR-268298 |
P67870 | O60763 | 1 | phosphorylation | up-regulates activity | 0.335 | Phosphorylation is mediated by casein kinase II (CKII) or a CKII-like kinase. | Serine 941 in the Acidic Domain of p115 Is Essential for Reassembly of Golgi Cisternae | SIGNOR-251082 |
Q16584 | Q02750 | 1 | phosphorylation | up-regulates activity | 0.335 | Here we report that MLK3 can phosphorylate and activate MEK-1 directly in vitro and also can induce MEK phosphorylation on its activation sites in vivo in COS-7 cells. | SIGNOR-280019 |
Q05655 | Q13887 | 1 | phosphorylation | up-regulates activity | 0.335 | Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. | Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. | We found that KLF5s activity was reduced to half when the serine in the potential PKC phosphorylation site was mutated to alanine (Fig. 6B, S153A) Nonetheless, the S153A mutant still retains significant transactivation activity. | SIGNOR-249206 |
P04637 | P14672 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.335 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267465 |
P49715 | P49675 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.335 | Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. | SIGNOR-254043 |
Q99704 | P05106 | 1 | binding | down-regulates activity | 0.334 | Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation | SIGNOR-257687 |
P28482 | Q8NHW3 | 1 | phosphorylation | up-regulates activity | 0.334 | These residues are phosphorylated by erk2 but not by p38, jnk, and erk5 in vitro. However, the contribution of the mek/erk pathway to mafa phosphorylation in vivo appears to be moderate, implicating another kinase. The integrity of serine 14 and serine 65 residues is required for transcriptional activity, since their mutation into alanine severely impairs mafa capacity to activate transcription. | SIGNOR-108564 |
P68400 | Q01082 | 1 | phosphorylation | down-regulates | 0.334 | We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment. | SIGNOR-150471 |
Q05655 | P40189 | 1 | phosphorylation | up-regulates activity | 0.334 | Finally, we identified Thr-890, a putative PKC phosphorylation site on gp130, to be critical for the effect of PKCdelta. Our data indicate that PKCdelta plays important regulatory roles in IL-6 signaling. | SIGNOR-249177 |
Q13131 | P08151 | 1 | phosphorylation | down-regulates activity | 0.334 | AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This in turn leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency. | SIGNOR-259862 |
P17612 | O43665 | 1 | phosphorylation | down-regulates activity | 0.334 | We report in this study the acute functional regulation of rgs10 thru the specific and inducible phosphorylation of rgs10 protein at serine 168 by camp-dependent kinase a. This phosphorylation nullifies the rgs10 activity at the plasma membrane, which controls the g protein-dependent activation of the inwardly rectifying potassium channel. | SIGNOR-109173 |
P31943 | Q15554 | 1 | post transcriptional regulation | down-regulates quantity | 0.334 | During neuronal differentiation, use of an alternative splice site on the rat telomere repeat-binding factor 2 (TRF2) mRNA generates a short TRF2 protein isoform (TRF2-S) capable of derepressing neuronal genes. However, the RNA-binding proteins (RBPs) controlling this splicing event are unknown. Here, using affinity pull-down analysis, we identified heterogeneous nuclear ribonucleoproteins H1 and H2(HNRNPH) as RBPs specifically capable of interacting with the spliced RNA segment (exon 7) of Trf2 pre-mRNA. HNRNPH proteins prevent the production of the short isoform of Trf2 mRNA, as HNRNPH silencing selectively elevates TRF2-S levels. | SIGNOR-266807 |
Q16539 | P10415 | 1 | phosphorylation | down-regulates activity | 0.334 | Bcl-2 phosphorylation by p38 mapkin this study, we identify, by using mass spectrometry techniques and specific anti-phosphopeptide antibodies, ser(87) and thr(56) as the bcl-2 residues phosphorylated by p38 mapk and show that phosphorylation of these residues is always associated with a decrease in the antiapoptotic potential of bcl-2 protein. | SIGNOR-146786 |
P09429 | P28356 | 1 | binding | up-regulates activity | 0.334 | We show that HMG1 interacts with proteins encoded by the HOX gene family by establishing protein-protein contacts between the HMG box domains and the HOX homeodomain. The functional role of these interactions was studied using the transcriptional activity of the human HOXD9 protein as a model. HMG1 enhances, in a dose-dependent fashion, the sequence-specific DNA binding activity in vitro, and the transcriptional activation in a co-transfection assay in vivo, of the HOXD9 protein. | SIGNOR-236956 |
Q16254 | O15392 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.334 | This TGF-beta response is triggered through a Smad2/3-dependent hypophosphorylation of Rb and the subsequent association of the Rb/E2F4 repressive complex to CDE/CHR elements in the proximal region of the survivin promoter. | SIGNOR-271678 |
Q16539 | O00418 | 1 | phosphorylation | down-regulates activity | 0.334 | Inhibition of eEF2 kinase resulting from phosphorylation of Ser-396 by SAPK2a p38 was approx.25%. | SIGNOR-249707 |
Q00987 | P54253 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.334 | NICD and MDM2 ubiquitinate and degrade ATXN1.|These results suggest that NICD and MDM2 synergistically reduce ATXN1 expression at the posttranscriptional level. | SIGNOR-278823 |
Q8TEK3 | P01106 | 1 | binding | up-regulates activity | 0.334 | Our data suggest that the c-Myc-dependent transcriptional switch is modulated by DOT1L, as in the presence of DOT1L c-Myc preferentially forms an active complex with p300 rather than a repressive complex containing HDAC1 and DNMT1 | SIGNOR-239362 |
Q00987 | Q9GZR7 | 1 | polyubiquitination | up-regulates activity | 0.334 | MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing. | SIGNOR-272845 |
P23467 | Q9UM73 | 1 | dephosphorylation | down-regulates | 0.334 | Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation. | SIGNOR-157175 |
P55085 | P19086 | 1 | binding | up-regulates activity | 0.334 | 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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. | SIGNOR-257232 |
P49841 | P23760 | 1 | phosphorylation | up-regulates quantity | 0.334 | The ubiquitously expressed CK2 often provides the priming phosphorylation for GSK-3, however, we found that GSK-3beta alone was sufficient to phosphorylate PAX3 at both Ser205 and Ser197 and Ser201 in-vitro. | SIGNOR-278482 |
P49137 | Q9Y385 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.334 | Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFα production. These findings strongly suggest that MK2 directly phosphorylates Ube2j1 at Ser(184) upon p38-activating stress in vivo. | SIGNOR-263091 |
Q96PU5 | Q15858 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.334 | 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-253458 |
Q14012 | P49757 | 1 | phosphorylation | down-regulates | 0.334 | Based on experiments using numb mutants, both the initial phosphorylation of ser(264) and the subsequent phosphorylation of ser(283) are sufficient to abolish the binding of numb to ap-2. | SIGNOR-149993 |
Q15759 | P00533 | 1 | phosphorylation | down-regulates | 0.334 | P38 map kinase mediates stress-induced internalization of egfrthe underlying mechanism entails phosphorylation of egfr at a short segment (amino acids 1002-1022) containing multiple serines and threonines, as well as phosphorylation of two rab5 effectors, eea1 and gdi. | SIGNOR-149086 |
O75838 | Q8TDI8 | 1 | binding | up-regulates activity | 0.334 | Furthermore, we report that calcium and integrin-binding protein 2 binds to the components of the hair cell mechanotransduction complex, TMC1 and TMC2, and these interactions are disrupted by deafness-causing Cib2 mutations. We conclude that calcium and integrin-binding protein 2 is required for normal operation of the mechanotransducer channels and is involved in limiting the growth of transducing stereocilia. | SIGNOR-269664 |
O75914 | P17600 | 1 | phosphorylation | up-regulates activity | 0.334 | Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release | SIGNOR-250246 |
O00311 | O75475 | 1 | phosphorylation | up-regulates | 0.334 | We now report identification of the cdc7-activator of s-phase kinase (ask) heterodimer as a novel interactor of ledgf. the kinase phosphorylated ledgf in vitro, with ser-206 being the major target, and ledgf phosphorylated at this residue could be detected during s phase of the cell cycle. Ledgf potently stimulated the enzymatic activity of cdc7-ask, increasing phosphorylation of mcm2 in vitro by more than 10-fold. | SIGNOR-25763 |
P12931 | O43255 | 1 | phosphorylation | up-regulates activity | 0.334 | In human breast cancer cell lines, the protein kinase Src has been shown to activate Siah2 by phosphorylation of tyrosines 86, 140, and 263.|This function is promoted by Src phosphorylation of Siah2, which increases C/EBPdelta binding, ubiquitination, and degradation. | SIGNOR-279555 |
Q8IW41 | P47712 | 1 | phosphorylation | up-regulates activity | 0.334 | The p38-activated protein kinases MNK1, MSK1, and PRAK1 phosphorylate cPLA2 in vitro uniquely on Ser-727. By using Chinese hamster ovary, HeLa, and HEK293 cells stably transfected with wild type and phosphorylation site mutant forms of cPLA2, we show that phosphorylation of cPLA2 at both Ser-505 and Ser-727 and elevation of Ca(2+) leads to its activation in agonist-stimulated cells. | SIGNOR-250162 |
P17612 | O14921 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.334 | Phosphorylation of RGS13 by the cyclic AMP-dependent protein kinase inhibits RGS13 degradation.we show that PKA activation also leads to increased steady-state RGS13 expression through RGS13 phosphorylation, which inhibits RGS13 protein degradation. RGS13 phosphorylation was diminished by mutation of an N-terminal Thr residue (T41) identified as a phosphorylation site by mass spectrometry. | SIGNOR-259835 |
P07948 | O75807 | 1 | phosphorylation | up-regulates | 0.334 | Gadd34 was tyrosine-phosphorylated in vivo in a lyn-dependent manner. | SIGNOR-109934 |
Q08881 | P51813 | 1 | phosphorylation | up-regulates activity | 0.334 | Itk phosphorylated Bmx-SH3 to a low extent. pY positions correspond to the residues Y215 and Y223 in Bmx. Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. | SIGNOR-251331 |
P42684 | O15304 | 1 | phosphorylation | up-regulates | 0.334 | Our results also demonstrate that mutation of the siva-1 tyr48 site abrogates the apoptotic function of siva-1 and that apoptosis induced by siva-1 is dependent on expression of kinase-active arg. | SIGNOR-104992 |
Q04759 | P32942 | 1 | 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 |
Q8IZD2 | P10276 | 1 | binding | up-regulates activity | 0.334 | MLL5 binds to retinoic acid receptor α (RARα) and induces transcriptional activation of RARα target genes by methylation of lysine residues of histone H3. | SIGNOR-260041 |
Q12981 | Q13501 | 1 | binding | up-regulates activity | 0.334 | RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. BNIP1 is polyubiquitinated by RNF185 and associates with autophagy receptor p62. In addition, we checked the endogenous localization of BNIP1 and p62 in HeLa cells (Fig. 7F). Alexa Fluor 488 conjugated endogenous BNIP1 and TRITIC conjugated endogenous p62 overlapped well in the cytoplasm, further providing the locational evidence for the recruitment of p62 by BNIP1. | SIGNOR-271932 |
P41134 | P31749 | 1 | binding | up-regulates | 0.334 | We have determined that Id1 physically interacts with AKT1, through its C-terminal region, and promotes AKT1 phosphorylation; | SIGNOR-255658 |
Q9UER7 | O43918 | 1 | binding | down-regulates activity | 0.334 | The interaction between AIRE and DAXX has been validated by in vivo coimmunoprecipitation analysis and colocalization study in mammalian cells. The interaction has been further confirmed by showing in transactivation assays that DAXX exerts a strong repressive role on the transcriptional activity of AIRE. | SIGNOR-239287 |
O15021 | Q12778 | 1 | phosphorylation | down-regulates activity | 0.334 | MAST4 phosphorylation of FOXO1 regulates RTKN2 expression. | SIGNOR-279079 |
P00533 | Q04912 | 1 | phosphorylation | up-regulates activity | 0.334 | This showed that EGFR activation transphosphorylated Ron.|Together, these data suggested that (1) Ron activation transphosphorylated EGFR and vice versa and (2) activated Ron biochemically interacted with EGFR. | SIGNOR-280000 |
P17252 | Q9UEY8 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.334 | Results of in vitro experiments with recombinant alpha adducin demonstrated that PKC-phosphorylated adducin was proteolyzed by calpain more quickly than unphosphorylated adducin. | Phosphorylation of adducin by PKC may be a common mechanism for regulating adducin proteolysis by several proteases. | The antibody used in panel B is specific for the PKC-phosphorylated form of adducin. This antibody was raised against the phosphopeptide CKKFRTP[pS]FLKKNK, corresponding to amino acids 656-668 of human gamma adducin | SIGNOR-249143 |
Q15139 | P23528 | 1 | phosphorylation | down-regulates activity | 0.334 | PKD1 regulates cofilin S3-phosphorylation|Both, oxidative stress as well as RhoA activation enhanced cofilin phosphorylation at S3, implicating an increased inhibition due to PKD1-mediated signalling events | SIGNOR-275944 |
P68400 | P06744 | 1 | phosphorylation | down-regulates activity | 0.333 | It is known that human PGI/AMF is phosphorylated at Ser(185) by protein kinase CK2 (CK2) | These results demonstrate that phosphorylation affects the allosteric kinetic properties of the enzyme, resulting in a less active form of PGI, whereas non-phosphorylated protein species retain cytokine activity. | SIGNOR-250869 |
P48729 | P30304 | 1 | phosphorylation | down-regulates | 0.333 | Here, we report that casein kinase 1 alpha (ck1alpha) phosphorylates cdc25a on both s79 and s82 in a hierarchical manner requiring prior phosphorylation of s76 by chk1 or gsk-3beta. This facilitates beta-trcp binding and ubiquitin-mediated proteolysis of cdc25a | SIGNOR-164734 |
P00519 | P12004 | 1 | phosphorylation | up-regulates activity | 0.333 | In the current study, we are able to establish a new pathway in which the Ron receptor tyrosine kinase activates c-Abl which in turn catalyzes Y211 phosphorylation of PCNA.|We previously showed that Y211 phosphorylation stabilized chromatin bound PCNA, which in turn promoted cell proliferation, and that c-Abl functioned to enhance chromatin association of PCNA in cancer cells. | SIGNOR-279389 |
P46937 | O14640 | 1 | binding | down-regulates | 0.333 | Yap restricts elevated wnt independently of the axinapcgsk-3beta complex partly by limiting the activity of dishevelled (dvl). | SIGNOR-199806 |
P67775 | Q13315 | 1 | dephosphorylation | down-regulates activity | 0.333 | Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro. | SIGNOR-248644 |
P06493 | Q8IWB6 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.333 | Cdk1 phosphorylation of Tex14 is required for the Tex14-Plk1 interaction | SIGNOR-273524 |
P06241 | Q15417 | 1 | phosphorylation | down-regulates activity | 0.333 | We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin | SIGNOR-251159 |
P48730 | P53041 | 1 | phosphorylation | up-regulates activity | 0.333 | Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90. | SIGNOR-277373 |
P62136 | O15169 | 1 | dephosphorylation | down-regulates activity | 0.333 | The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin| Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity| Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated | SIGNOR-248551 |
Q8NCQ5 | Q9UJA2 | 1 | binding | down-regulates quantity by destabilization | 0.333 | Fbxo15 Targets CLS1 Protein for Ubiquitination and Degradation to Disrupt Mitochondrial Function. S. aureus infection induces expression of a kinase, PINK1, that phosphorylates an indispensable protein CLS1, which in turn triggers CLS1 ubiquitination and degradation by the F box protein (SCFFbxo15). | SIGNOR-272170 |
P48357 | Q9NRF2 | 1 | binding | up-regulates activity | 0.333 | The SH2B adaptor protein 1 (SH2B1) is a key regulator of leptin, as it enhances leptin signalling by both stimulating Janus kinase 2 (JAK2) activity and assembling a JAK2/IRS1/2 signalling complex | SIGNOR-253077 |
P98170 | P57078 | 1 | polyubiquitination | up-regulates activity | 0.333 | In this study, we report that in addition to RIP1 and RIP2, also RIP3 and RIP4 directly interact with XIAP, cIAP1 and cIAP2. When comparing the ability of these IAPs to directly conjugate RIP1–RIP4 with ubiquitin chains, we found that cIAP1 was the most effective E3 and was capable of ubiquitinating all four RIPs in the presence of the E2 component UbcH5a. On the contrary, XIAP was only capable of inducing weak ubiquitination of RIP4. | SIGNOR-272716 |
Q02779 | Q13562 | 1 | binding | up-regulates activity | 0.333 | we identified two proteins that interact with ND, huntingtin-associated protein 1 (HAP1) and mixed-lineage kinase 2 (MLK2). Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2 | SIGNOR-234599 |
Q14012 | O00429 | 1 | phosphorylation | up-regulates activity | 0.333 | For example, protein kinase A (PKA) phosphorylation of Drp1S600 has been reported to decrease Drp1 GTPase activity in vitro (23, 24), whereas phosphorylation of the same conserved serine residue by Ca2+-calmodulin–dependent protein kinase Iα (CaMKIα) in Drp1 isoform 3 has been reported to cause a significant increase in mitochondrial fission | SIGNOR-262552 |
Q9UHD9 | Q00839 | 1 | binding | up-regulates quantity by stabilization | 0.333 | Confirmation of binding of recombinant full-length hnRNPA1 and hnRNPU proteins with ubiquilin-2 by GST-pull-down assays|Additionally, our evidence that ubiquilin-2 is in- volved in stabilizing hnRNPA1 protein | SIGNOR-262271 |
Q8N752 | P10070 | 1 | phosphorylation | up-regulates | 0.333 | Gli2 is phosphorylated by gsk3 and ck1 for the fbxw11 (betatrcp2)-mediated degradation ci is phosphorylated by pka at multiple sites priming phosphorylation by both gsk3 and cki, leading to partial proteolysis. The pka, gsk3, and cki sites are conserved in gli2 and gli3, vertebrate homologs of ci that are similarly processed | SIGNOR-179972 |
Q8N752 | P10071 | 1 | phosphorylation | up-regulates | 0.333 | Ci is phosphorylated by pka at multiple sites priming phosphorylation by both gsk3 and cki, leading to partial proteolysis. The pka, gsk3, and cki sites are conserved in gli2 and gli3, vertebrate homologs of ci that are similarly processed | SIGNOR-144554 |
O94921 | O75581 | 1 | phosphorylation | up-regulates | 0.333 | Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6. | SIGNOR-162924 |
P19784 | Q13541 | 1 | phosphorylation | down-regulates activity | 0.333 | The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these kinases in the phosphorylation of 4E-BP1 in fat cells is discussed. It is suggested that the phosphorylation of Ser-111 might be a priming event that facilitates the subsequent phosphorylation of Thr-36, Thr-45, Ser-64 and Thr69 by a rapamycin-sensitive process that initiates the dissociation of 4E-BP1 from eIF4E and hence the formation of the eIF4F complex. | SIGNOR-249334 |
Q05193 | P08247 | 1 | binding | up-regulates activity | 0.333 | The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis. Our observation that dynamin binds to the SV protein synaptophysin in a Ca2+-dependent fashion suggested the possibility that a dynamin/synaptophysin complex functions in SV recycling. | SIGNOR-264119 |
Q96EP1 | P51532 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination. | SIGNOR-271457 |
P68400 | P08238 | 1 | phosphorylation | down-regulates | 0.333 | Although the kinase responsible for hsp90? Phosphorylation in vivo is not known, it has been reported that ck2 can phosphorylate these sites in vitro (24). Thus, we prephosphorylated recombinant hsp90? With ck2 before addition to the reaction. Remarkably, hsp90? Phosphorylation greatly reduced its ability to inhibit apaf-1 oligomerization and caspase-9 recruitment (fig. 5b). These results indicate that the phosphorylation status of hsp90? Significantly impacts its ability to inhibit apoptosome formation. | SIGNOR-179264 |
Q00536 | P46527 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.333 | In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells.|Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target. | SIGNOR-273016 |
P07384 | P10636 | 1 | cleavage | down-regulates activity | 0.333 | Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains | SIGNOR-251584 |
P09629 | P78527 | 1 | binding | up-regulates activity | 0.333 | Ku70 and Ku80 associated with HOXB7 in vivo. Ku70/Ku80 heterodimer formation is a prerequisite for HOXB7 binding. interaction between Ku70/80 and HOXB7 may affect the catalytic activity of DNA-PK. HOXB7 stimulates DNA-PK activity | SIGNOR-226063 |
Q9Y5B0 | P06493 | 1 | dephosphorylation | down-regulates activity | 0.333 | Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.|We can not exclude that, in addition to S90 and S453, other Cdk1 phosphorylation sites in Gwl are dephosphorylated by Fcp1; nevertheless, assaying S67-Ensa kinase activity of V5-GwlS90A and V5-GwlS453A mutant proteins, isolated from transfected and prometaphase arrested HeLa cells, revealed that both mutants had significantly reduced S67-Ensa kinase activity compared to V5-GwlWT (XREF_FIG).|We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. | SIGNOR-277141 |
Q9UBS0 | Q15633 | 1 | phosphorylation | up-regulates activity | 0.333 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274066 |
P17612 | P04035 | 1 | phosphorylation | down-regulates activity | 0.333 | The intact, 100 kd microsomal enzyme and the 53 kd catalytic fragment of rat HMG-CoA reductase are both phosphorylated and inactivated by the AMP-activated protein kinase. this site is highly phosphorylated in intact liver under these conditions (Ser872 in the human enzyme). | SIGNOR-249992 |
P42679 | P07948 | 1 | phosphorylation | down-regulates activity | 0.333 | In vitro phosphorylation assays showed that Chk suppressed Lyn activity by phosphorylating its C-terminal negative regulatory tyrosine. | SIGNOR-250177 |
Q05193 | Q12965 | 1 | binding | up-regulates activity | 0.333 | We describe binding of two PRD-containing endocytic proteins, dynamin and synaptojanin-1, to the SH3 domain of Myo1E. This interaction was detected both in vitro, using pull-downs of purified proteins, and in vivo, using immunoprecipitation of protein complexes from synapse-enriched brain extract and immunolocalization of Myo1E and dynamin. Our observation of the interaction between human Myo1E and endocytic proteins suggests that this longtailed myosin may play a role in clathrin-dependent endocytosis.Interaction between Myo1E SH3 domain and PRD-containing endocytic proteins may promote recruitment of Myo1E to clathrin-coated structures since an inactivating mutation in the SH3 domain reduced Myo1E localization to clathrin-containing puncta. | SIGNOR-265424 |
Q13490 | P55060 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | We find that TRAIL induces up-regulation of CAS in a posttranscriptional, caspase-8-dependent manner through degradation of cIAP1, an E3 ligase that targets CAS for ubiquitin-dependent proteasomal degradation. | SIGNOR-272812 |
Q8N488 | P00519 | 1 | binding | down-regulates | 0.333 | We identified a novel protein, aap1 (abl-associated protein 1), that associates with these c-abl domains and fails to bind to the sh3 domain in the activated oncoprotein bcrabl. we conclude that aap1 inhibits c-abl tyrosine kinase activity | SIGNOR-45325 |
P06241 | P51911 | 1 | phosphorylation | down-regulates activity | 0.333 | We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin | SIGNOR-251157 |
O60729 | P04637 | 1 | dephosphorylation | down-regulates activity | 0.333 | The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53|. Furthermore, the hCdc14 phosphatases were found to dephosphorylate p53 specifically at the p34Cdc2/clb phosphorylation site (p53-phosphor-Ser315)|Earlier studies showed that Ser315 phosphorylation increases the sequence-specific DNA binding capacity of p53, suggesting that Ser315 phosphorylation is an activating modification | SIGNOR-248332 |
Q86VS8 | P21757 | 1 | binding | down-regulates | 0.333 | We have identified a microtubule-binding protein, hook3, as a novel interacting partner of sr-a. / by transfecting small interfering rna targeting hook3, total and surface expression, receptor-mediated ligand uptake and protein stability of sr-a were significantly promoted, whereas the protein synthesis and maturation were not altered. We propose for the first time that hook3 may participate in the turnover of the endocytosed scavenger receptor | SIGNOR-152314 |
P68400 | Q06413 | 1 | phosphorylation | up-regulates activity | 0.333 | We show that serine 59 located between the MADS and MEF2 domains of MEF2C is phosphorylated in vivo and can be phosphorylated in vitro by casein kinase-II (CKII). Phosphorylation of this site enhanced the DNA binding and transcriptional activity of MEF2C by increasing its DNA binding activity 5-fold. | SIGNOR-250914 |
P98161 | Q8IUQ4 | 1 | binding | up-regulates activity | 0.333 | Full-length PC1 bound, stabilized and colocalized with Jade-1 and inhibited Jade-1 ubiquitination. Jade-1 ubiquitination was mediated by Siah-1, an E3 ligase that binds PC1. | SIGNOR-272916 |
Q6ISU1 | P06239 | 1 | binding | up-regulates activity | 0.333 | However, non-canonical mechanisms of p38alfa activation have been also described. One is apparently specific to antigen receptor stimulated t-lymphocytes. This involves phosphorylation of p38alfa on tyr323 by the tcr-proximal tyrosine kinase zap70 and p56lck. | SIGNOR-166658 |
P48729 | Q13158 | 1 | phosphorylation | down-regulates activity | 0.333 | FADD is essential for death receptor (DR)-induced apoptosis.|Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities | SIGNOR-139307 |
O14920 | Q15672 | 1 | phosphorylation | down-regulates activity | 0.332 | Hence, our current study supports the pivotal role of beta-TRCP in IKKbeta mediated Twist degradation.|More importantly, IKK\u03b2-dependent phosphorylation of Twist at T125 and S127 governs its nuclear localization. | SIGNOR-278404 |
Q13043 | Q15208 | 1 | phosphorylation | up-regulates activity | 0.332 | Although MST1, MST2, and MST3 potently activated NDR1 in vitro, MST4 had only a minor effect.|Indeed, NDR1 phosphorylated at Thr444 by MST1 displayed greatly (7-fold) enhanced protein kinase activity. | SIGNOR-279641 |
P68400 | O75925 | 1 | phosphorylation | up-regulates | 0.332 | Ck2 phosphorylates serine residues adjacent to the sim of pias1 these findings show that the phosphosim module mediates binding to free sumo and sumo conjugates in a phosphorylation-dependent mode, with ck2 being the critical kinase involvedin this process. | SIGNOR-184047 |
Q13555 | P07101 | 1 | phosphorylation | up-regulates activity | 0.332 | In both isoforms, Ser-40 was found to be phosphorylated by PKA, and Ser-19 and Ser-40 were found to be phosphorylated by CaM-PK II. The putative phosphorylation site generated by alternative splicing (Ser-31) was phosphorylated specifically by CaM-PK II in TH-2 only. | Unlike TH-1, phosphorylation of TH-2 by CaM-PK II resulted in an increase of the Ki value for dopamine. | SIGNOR-250709 |
P17252 | P48067-2 | 1 | phosphorylation | down-regulates activity | 0.332 | We demonstrated that the isoforms GlyT1a, GlyT1b, and GlyT1c were constitutively phosphorylated, and that phosphorylation was dramatically enhanced, in a time dependent fashion, after PKC activation by phorbol ester. The phosphorylation was PKC-dependent, since pre-incubation of the cells with bisindolylmaleimide I, a selective PKC inhibitor, abolished the phorbol ester-induced phosphorylation. Blotting with specific anti-phospho-tyrosine antibodies did not yield any signal that could correspond to GlyT1 tyrosine phosphorylation, suggesting that the phosphorylation occurs at serine and/or threonine residues. These results together suggest that conventional PKCα and/or β are responsible for the downregulation of glycine transport. We further analyzed the effect of more specific inhibitors to PKCα and PKCβ on the GlyT1 activity. As shown in Fig. 4, panels C-F, incubation of the cells with varying concentrations of the PKCβ inhibitors (referred as PKCβ inhibitor and LY333531) or the PKCα/γ (HDBBE) inhibitors did not prevent the reduction of glycine uptake triggered by PMA, suggesting that PKCα and PKCβ together regulate GlyT1 activity. | SIGNOR-262919 |
Q15139 | Q96P20 | 1 | phosphorylation | up-regulates activity | 0.332 | PKD at the Golgi phosphorylates NLRP3 to release it from mitochondria-associated endoplasmic reticulum membranes, allowing for assembly of the mature inflammasome in the cytosol.|These data thus suggest that PKD activity at the Golgi is sufficient to activate the NLRP3 inflammasome. | SIGNOR-279428 |
O14920 | P23396 | 1 | phosphorylation | up-regulates activity | 0.332 | IKKbeta overexpression activated NF-kappaB measured by luciferase assays , and also induced the nuclear translocation of wild-type, but not S209A, RPS3 (XREF_FIG).|Therefore, RPS3 S209 phosphorylation by IKK\u03b2 is apparently required for RPS3 in directing NF-\u03baB to a specific subset of target genes. | SIGNOR-278360 |
P42680 | P51813 | 1 | phosphorylation | up-regulates activity | 0.332 | Tec family protein tyrosine kinases (TFKs) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop.The major phosphorylation sites were identified as conserved tyrosines, for Itk Y180 and for Bmx Y215, both sites being homologous to the Y223 site in Btk | SIGNOR-246647 |
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