IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
P49137 | Q13151 | 1 | phosphorylation | up-regulates activity | 0.531 | MAPKAP-K2 phosphorylated hnRNP A0 at Ser84 in vitro and this residue became phosphorylated in LPS-stimulated cells. The simplest explanation for these findings is that the phosphorylation of hnRNP A0 at Ser84 by MAPKAP-K2 enhances binding to the AREs of these mRNAs or allows hnRNP A0 to displace another protein(s) from the AREs. | SIGNOR-262951 |
O15111 | P31749 | 0 | phosphorylation | up-regulates | 0.668 | Although there are likely to be multiple levels of crosstalk between the pi3k-akt and nf-kb pathways, one mechanism has been attributed to direct phosphorylation of the amino acid residue t23 on ikb kinase alfa (ikkalfa) by akt, thereby leading to activation of this kinase upstream of nf-kb akt mediates ikkalpha phosphorylation at threonine 23 akt transiently associates in vivo with ikk and induces ikk activation. Akt mediates ikkalfa phosphorylation at threonine 23.Akt phosphorylates ikkalpha on t23, and this phosphorylation event is a prerequisite for the phosphorylation of p65 at s534 by ikkalpha and beta | SIGNOR-187006 |
P01137 | P37173 | 2 | binding | up-regulates activity | 0.853 | A cdna encoding the tgf-beta type ii receptor protein has been isolated by an expression cloning strategy. The cloned cdna, when transfected into cos cells, leads to overexpression of an approximately 80 kd protein that specifically binds radioiodinated tgf-beta 1. Excess tgf-beta 1 competes for binding of radioiodinated tgf-beta 1 in a dose-dependent manner and is more effective than tgf-beta 2. | SIGNOR-236080 |
O75122 | P00519 | 0 | phosphorylation | up-regulates quantity | 0.502 | We find that Abl binds to and phosphorylates CLASP2 in response to extracellular signals such as serum or PDGF. | SIGNOR-279580 |
Q02156 | P10636-2 | 1 | phosphorylation | down-regulates activity | 0.271 | We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs. | SIGNOR-275444 |
Q14493 | P68400 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.328 | Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation. | SIGNOR-265260 |
P05556 | Q9Y5I3 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265663 |
P15056 | P62834 | 2 | binding | up-regulates activity | 0.692 | Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity.Increased intracellular concentrations of cAMP enhanced the Rapgef2-dependent activation of Rap1, which in turn associated with B-Raf to enable the activation of ERK and subsequent neuronal- and endocrine-specific cellular outcomes, such as induction of neuroendocrine-specific genes and extension of neuritic processes (neuritogenesis). | SIGNOR-276608 |
Q96GD4 | P56524 | 1 | phosphorylation | down-regulates | 0.264 | We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions | SIGNOR-198646 |
P62993 | Q8WU20 | 2 | binding | up-regulates activity | 0.802 | In this report, we demonstrate that FGF stimulation induces tyrosine phosphorylation of a novel lipid anchored docking protein, termed FRS2, that forms a complex with Grb2/Sos, thus linking FGF-receptor activation to the Ras/MAPK signaling pathway. | SIGNOR-236953 |
P12931 | P15498 | 1 | phosphorylation | up-regulates activity | 0.368 | These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ). | SIGNOR-279124 |
P52566 | P17252 | 0 | phosphorylation | down-regulates | 0.2 | These results reveal a mechanism of downregulation of rhogdi2 activity through pkc-mediated phosphorylation of ser31. | SIGNOR-196765 |
Q13873 | Q04771 | 2 | binding | up-regulates | 0.714 | Bmpr-ii is a transmembrane serine/threonine kinase that binds bmp-2 and bmp-7 in association with multiple type i receptors, including bmpr-ia/brk1, bmpr-ib, and actr-i, which is also an activin type i receptor. | SIGNOR-33434 |
Q13387 | O14733 | 2 | binding | up-regulates | 0.678 | Thus, both jip1 and jip2 selectively bind the mapkk isoform mkk7. | SIGNOR-59944 |
Q8NEL9 | P68400 | 0 | phosphorylation | down-regulates activity | 0.2 | Here we incubated a recombinant preparation of the phospholipase in vitro with several enzymes including protein kinase CK2 (CK2), extracellular signal-regulated kinase 2 (ERK2), and protein phosphatase 2A (PP2A) to identify effects that might be of regulatory importance in vivo.Major findings were that 1) CK2 phosphorylated the phospholipase on serines 93, 105, and 716; 2) ERK2 phosphorylated the enzyme on serine 730; 3) there was cross-antagonism between the reactions that phosphorylated serines 716 and 730; 4) PP2A selectively hydrolyzed phosphate groups that were esterified to serines 716 and 730. The results of two independent experiments with each type of assay indicated that the incubation caused a 50% loss of phospholipase activity (TableV). These results differed from those of corresponding incubation experiments with PA-PLA1α plus ERK2 and MgATP (see “Experimental Procedures”), which provided no evidence for complex formation or phosphorylation-dependent loss of phospholipase activity | SIGNOR-262977 |
Q9UBZ9 | Q12834 | 2 | binding | down-regulates quantity by destabilization | 0.273 | Here, we show that human REV1 undergoes proteosomal degradation mediated by the E3 ubiquitin ligase known as anaphase-promoting complex (APC). REV1 associates with APC. Overexpression of APC coactivator CDH1 or CDC20 promotes polyubiquitination and proteosomal degradation of REV1. | SIGNOR-272892 |
Q12834 | P06493 | 0 | phosphorylation | down-regulates activity | 0.935 | Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C. | SIGNOR-279321 |
Q15831 | Q96EB6 | 1 | phosphorylation | up-regulates activity | 0.573 | Resveratrol promotes the binding between LKB1 and Sirt1, which we first reported, and this binding leads to LKB1-mediated phosphorylation of Sirt1 at three different serine residues in the C terminus of Sirt1. Mechanistically, LKB1-mediated phosphorylation increases intramolecular interactions in Sirt1, such as the binding of the C terminus to the deacetylase core domain, thereby eliminating DBC1 (Deleted in Breast Cancer 1, Sirt1 endogenous inhibitor) inhibition and promoting Sirt1-substrate interaction. | SIGNOR-277323 |
O75197 | P09544 | 2 | binding | up-regulates | 0.611 | 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-131727 |
O14733 | Q9UL54 | 2 | binding | up-regulates | 0.2 | Immunoprecipitated psk phosphorylates myelin basic protein and transfected psk stimulates mkk4 and mkk7 and activates the c-jun n-terminal kinase mitogen-activated protein kinase pathway. | SIGNOR-74867 |
Q92560 | P42772 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Since we found that ASXL1 and BAP1 both are enriched at the INK4B locus, our results suggest that activation of the INK4B locus requires ASXL1/BAP1-mediated deubiquitinylation of H2AK119ub1. | SIGNOR-241656 |
P63104 | P17612 | 0 | phosphorylation | down-regulates activity | 0.566 | Phosphorylation by pka leads to modulation of 14-3-3zeta dimerization and affect its interaction with partner proteins. Substitution of ser58 to ala completely abolished phosphorylation of 14-3-3zeta by pka. | SIGNOR-143373 |
P53350 | Q12888 | 1 | phosphorylation | down-regulates activity | 0.596 | Here we show that 53BP1 is phosphorylated during mitosis on two residues, T1609 and S1618, located in its well-conserved ubiquitination-dependent recruitment (UDR) motif.|Dephosphorylation enables the recruitment of 53BP1 to double-strand DNA breaks |Addition of the inhibitors for PLK1 and the p38 MAPK leads to a complete loss of pT1609/pS1618 signal within 3 hr in mitotic cells | SIGNOR-264413 |
P42574 | O14920 | 1 | cleavage | down-regulates | 0.364 | Ikappab kinase (ikk) beta was specifically proteolyzed by caspase-3-related caspases at aspartic acid residues 78, 242, 373, and 546 during tumor necrosis factor (tnf)-alpha-induced apoptosis. | SIGNOR-112792 |
Q14653 | P42684 | 0 | phosphorylation | up-regulates activity | 0.2 | The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. | SIGNOR-277441 |
P46663 | P30679 | 2 | binding | up-regulates activity | 0.449 | 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-257411 |
P46937 | P26232 | 2 | binding | down-regulates | 0.329 | The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation. | SIGNOR-201245 |
P35222 | Q9Y2T1 | 2 | binding | down-regulates | 0.848 | It has been found that a multiprotein complex assembled by the cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin. The complex includes apc, the serine/threonine kinase gsk3 beta, and beta-catenin, which bind to conductin at distinct domains. | SIGNOR-79947 |
O96014 | O15146 | 2 | binding | up-regulates | 0.456 | Musk has an extracellular region with homology to the frizzled crd,binding of which by wnt11 stimulates a pcp-like pathway during neuromuscolar development. Here, we show that in vivo, wnt11r and wnt4a initiate musk translocation from muscle membranes to recycling endosomes we provide evidence that wnt9a and wnt11 bind directly to the extracellular domain of musk, to induce musk dimerization and subsequent tyrosine phosphorylation of the kinase | SIGNOR-199641 |
P08581 | Q13588 | 2 | binding | up-regulates | 0.269 | To efficiently promote transformation met requires direct binding with grb2. | SIGNOR-42358 |
Q01543 | Q09472 | 2 | binding | up-regulates | 0.291 | P300 promotes the interaction of fli1 with hdac1 and increases the dna binding ability of fli1 through deacetylation of lysine 380 | SIGNOR-202682 |
P38405 | P34995 | 2 | binding | up-regulates activity | 0.25 | 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-256954 |
P08754 | P41143 | 2 | binding | up-regulates activity | 0.461 | 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-256826 |
Q99623 | P31749 | 2 | binding | down-regulates | 0.485 | Akt binds prohibitin 2 and relieves its repression of myod and muscle differentiation | SIGNOR-252541 |
Q02156 | P05091 | 1 | phosphorylation | up-regulates activity | 0.281 | Post-translational enhancement of ALDH2 activity can be achieved by serine/threonine phosphorylation by epsilon protein kinase C (epsilonPKC). |e identified S279 as a critical εPKC phosphorylation site in the activation of ALDH2. The critical catalytic site, cysteine 302 (C302) of ALDH2 is susceptible to adduct formation by reactive aldehyde, 4HNE, which readily renders the enzyme inactive. We show that phosphomimetic mutations of T185E, S279E and T412E confer protection of ALDH2 against 4HNE-induced inactivation, indicating that phosphorylation on these three sites by εPKC likely also protects the enzyme against reactive aldehydes. | SIGNOR-271864 |
Q9NR31 | Q15437 | 2 | binding | up-regulates quantity | 0.677 | Biogenesis of COPII vesicles is initiated by the activation of the small guanosine triphosphate (GTP)-binding protein secretion-associated Ras-related protein 1 (Sar1) at specialized subdomains of the ER, called ER exit sites (ERES) or transitional ER (tER). Membrane-bound Sar1 then recruits the inner COPII coat subcomplex, the Sec23/24 heterodimer. | SIGNOR-265298 |
P31749 | Q8N6T7 | 1 | phosphorylation | down-regulates activity | 0.532 | AKT1 interacts with and phosphorylates SIRT6 on Ser 338.|Because AKT1 suppresses SIRT6 protein abundance by decreasing its stability, we investigated whether MDM2 is involved in this process. | SIGNOR-278465 |
P40426 | P17481 | 2 | binding | up-regulates activity | 0.484 | the ability of HoxB8 to heterodimerizes with endogenous Pbx proteins on DNA alters gene transcription in a manner that prevents progression through an intrinsic genetic differentiation program. In conjunction with Pbx, HoxB8 could alter transcription of Pbx target genes by direct or indirect mechanisms. | SIGNOR-223149 |
P49841 | Q92915 | 1 | phosphorylation | up-regulates activity | 0.259 | Our laboratory has also demonstrated that FGF14 is a key accessory protein that binds to the intracellular Nav1.6 C-terminal tail, and that GSK3β can phosphorylate FGF14 both in vitro and in vivo at S226 [20] in an experimental model of Alzheimer's disease | SIGNOR-275746 |
Q15366 | P27361 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.323 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262916 |
P27361 | Q9BUB5 | 1 | phosphorylation | up-regulates | 0.576 | Mnk1 was phosphorylated and activated in vitro by erk1 and p38 map kinasespreliminary results showed that thr344 at least was one of the major sites phosphorylated by erk1 | SIGNOR-48360 |
P23396 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | Here we show that PKCδ phosphorylates rpS3 resulting in its mobilization in the nucleus to repair damaged DNA | SIGNOR-260895 |
Q9Y297 | Q13131 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Glucose deprivation activates AMPK kinase to phosphorylate β-TrCP1 and promotes the subsequent ubiquitination and degradation of β-TrCP1 by β-TrCP2, but does not promote β-TrCP2 degradation by β-TrCP1. | SIGNOR-277475 |
P16234 | P12931 | 1 | phosphorylation | up-regulates activity | 0.49 | The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells. | SIGNOR-247984 |
Q9UI95 | Q12834 | 2 | binding | down-regulates activity | 0.459 | The APC is activated in mitosis and G1 by CDC20 and CDH1, and inhibited by the checkpoint protein MAD2, a specific inhibitor of CDC20. We show here that a MAD2 homolog MAD2B also inhibits APC. MAD2B directly inhibits activation of APC by CDC20 and CDH1 | SIGNOR-264903 |
P23443 | P07814 | 1 | phosphorylation | up-regulates activity | 0.2 | Our studies reveal an unexpected adipogenic pathway resulting from mTORC1-S6K1 activation of EPRS ( xref ).|These results establish the requirement for mTORC1-activated S6K1 to phosphorylate EPRS at Ser 999 ( xref ). | SIGNOR-279483 |
O14757 | O00311 | 1 | phosphorylation | up-regulates | 0.734 | Chk1 directly phosphorylates essential s-phase kinases cdc7. | SIGNOR-163161 |
Q9GZQ4 | Q03113 | 2 | binding | up-regulates activity | 0.25 | 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-257402 |
Q92731 | P06850 | 1 | 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 |
P05787 | P53778 | 0 | phosphorylation | up-regulates | 0.2 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114067 |
P04150 | O00141 | 0 | phosphorylation | up-regulates activity | 0.46 | SGK1 also potentiated and maintained GR activation in the presence of cortisol, and even after cortisol withdrawal, by increasing GR phosphorylation and GR nuclear translocation|Having demonstrated that SGK1 mediates the cortisol-induced increase in GR phosphorylation at the S203 and S211 phospho-sites, which enhance GR nuclear translocation, but not at the S226 site, which inhibits nuclear translocation | SIGNOR-251669 |
P07550 | P31749 | 0 | phosphorylation | down-regulates | 0.354 | Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation. | SIGNOR-252470 |
O75385 | P06733 | 1 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274029 |
P08631 | P42768 | 1 | phosphorylation | up-regulates activity | 0.555 | Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function. | SIGNOR-273957 |
Q8N2W9 | Q13485 | 2 | binding | down-regulates | 0.558 | Piasy binds most strongly with smad3 and also associates with other receptor-regulated smads and smad4. smad3, smad4, and piasy can form a ternary complex. Piasy does not inhibit smad complex binding to dna, but it represses smad transcriptional activity. | SIGNOR-104541 |
P49674 | P55957 | 1 | phosphorylation | up-regulates activity | 0.345 | Here we report that Bid is phosphorylated by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed apoptosis. | These results suggest that residues S61, S64, and to a much lesser extent T58 are sites of phosphorylation of Bid. | SIGNOR-250806 |
Q5VT25 | P53671 | 1 | phosphorylation | up-regulates activity | 0.395 | These results indicate that mrckalpha phosphorylates and activates lim kinases downstream of cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of adf/cofilin. | SIGNOR-107584 |
Q00987 | P63092 | 2 | binding | down-regulates activity | 0.394 | Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content. | SIGNOR-278070 |
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 |
Q9P0L2 | P11137 | 1 | phosphorylation | down-regulates activity | 0.418 | Here we show that p110mark phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability. | SIGNOR-250166 |
Q96HZ4 | P68400 | 0 | phosphorylation | up-regulates activity | 0.498 | Hes6 inhibits the interaction of Hes1 with its transcriptional corepressor Gro/TLE. Moreover, it promotes proteolytic degradation of Hes1. This effect is maximal when both Hes1 and Hes6 contain the WRPW motif and is reduced when Hes6 is mutated to eliminate a conserved site (Ser183) that can be phosphorylated by protein kinase CK2. | SIGNOR-250890 |
P35916 | P49767 | 2 | binding | up-regulates | 0.935 | Vegf-c, was isolated as a ligand for the tyrosine kinase vegfr-3 (flt4) | SIGNOR-55205 |
P30291 | P48730 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.308 | Casein kinase 1-mediated N-terminal Weee1 phosphorylation is required for interaction with the F-box protein β-TrCP.MS/MS spectra of human Wee1 identifying serine 212 as phosphorylated after incubation with recombinant CK1δ. | SIGNOR-276631 |
P60953 | Q7Z5H3 | 0 | gtpase-activating protein | down-regulates activity | 0.543 | 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-260478 |
Q14683 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.705 | Atm phosphorylates Smc1 on serines 957 and 966 in vitro and in vivo, and expression of an Smc1 protein mutated at these phosphorylation sites abrogates the ionizing irradiation-induced S phase cell cycle checkpoint | SIGNOR-255589 |
Q9UPZ9 | P67775 | 0 | dephosphorylation | down-regulates | 0.2 | In addition, mass spectrometry showed that pp2a treatment completely abolished the dually phosphorylated form, leaving only the singly phosphorylated form (data not shown). We conclude that a portion of ick in unstimulated and asynchronized hek293t cells is dually phosphorylated on the tdy motif. | SIGNOR-138432 |
O15169 | O95996 | 2 | binding | up-regulates | 0.771 | Human axin (haxin) binds directly to beta-catenin, gsk3 beta, and apc in vitro, and the endogenous proteins are found in a complex in cells. | SIGNOR-57673 |
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 |
Q02363 | P15884 | 2 | binding | down-regulates activity | 0.596 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241376 |
P10721 | Q9NX45 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.325 | Our results suggest that SOHLH1 and SOHLH2 directly stimulate Kit transcription in postnatal spermatogonia, thus activating the signaling involved in spermatogonia differentiation and spermatogenetic progression. | SIGNOR-266206 |
P50613 | P41743 | 0 | phosphorylation | up-regulates activity | 0.343 | PKC\u03b9 activates CDK7 to promote glucose consumption.|PKC\u03b9 phosphorylates Thr170 on CDK7 in vitro, can associate with CDK7 in cells, and is activated downstream of PI3K signaling xref , xref \u2013 xref . | SIGNOR-280088 |
Q9NRA0 | P29466 | 2 | binding | up-regulates activity | 0.248 | Our data so far indicated colocalization of SphK2 with caspase-1 at the plasma membrane after induction of apoptosis.These observations supported caspase-1–dependent cleavage of SphK2 at its N-terminus as a prerequisite for its release. | SIGNOR-268831 |
P35354 | P06241 | 0 | phosphorylation | up-regulates activity | 0.389 | We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro. | SIGNOR-276644 |
Q86VW2 | P63000 | 1 | 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 |
P0DTC2 | O15393 | 0 | cleavage | up-regulates activity | 0.2 | Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. The Cellular Serine Protease TMPRSS2 Primes SARS-2- S for Entry, and a Serine Protease Inhibitor Blocks SARS-CoV-2 Infection of Lung Cells | SIGNOR-260736 |
O75582 | O75582 | 2 | phosphorylation | up-regulates activity | 0.2 | Msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758. Of these sites, the n-terminal t-loop residue ser-212 and the 'hydrophobic motif' ser-376 are phosphorylated by the c-terminal kinase domain of msk1, and their phosphorylation is essential for the catalytic activity of the n-terminal kinase domain of msk1 and therefore for the phosphorylation of msk1 substrates in vitro. | SIGNOR-131395 |
P19634 | Q16539 | 0 | phosphorylation | up-regulates | 0.571 | Trophic factor withdrawal: p38 mitogen-activated protein kinase activates nhe1, which induces intracellular alkalinization. activated p38 mapk directly phosphorylated the c terminus of nhe1 within a 40-amino-acid region. Analysis by mass spectroscopy identified four phosphorylation sites on nhe1, thr 717, ser 722, ser 725, and ser 728. | SIGNOR-111043 |
O75143 | Q8IYT8 | 2 | binding | up-regulates | 0.75 | He mammalian atg13 binds both ulk1 and ulk2 and mediates the interaction of the ulk proteins with fip200. The binding of atg13 stabilizes and activates ulk and facilitates the phosphorylation of fip200 by ulk | SIGNOR-184123 |
P46934 | Q13571 | 1 | ubiquitination | up-regulates activity | 0.476 | These results suggest that LAPTM5 ubiquitination is mediated by Nedd4.|Thus, Nedd4 promotes the recruitment of GGA3 to LAPTM5, allowing LAPTM5 translocation from the Golgi to the lysosome with the aid of GGA3. | SIGNOR-278768 |
P0C0L5 | O00187 | 0 | cleavage | up-regulates activity | 0.798 | MASP-2 cleaves C4 releasing C4a and generating C4b, which attaches covalently to the pathogen surface upon exposure of its reactive thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3 convertase (C4b2a). | SIGNOR-263422 |
Q15759 | O60271 | 2 | binding | up-regulates | 0.446 | Cdo, jlp, and p38alpha/beta form complexes in differentiating myoblasts, and cdo and jlp cooperate to enhance levels of active p38alpha/beta in transfectants. | SIGNOR-150147 |
Q9HAT8 | P51617 | 2 | ubiquitination | up-regulates | 0.781 | These studies suggest that pellino isoforms may be the e3 ubiquitin ligases that mediate the il-1-stimulated formation of k63-pub-irak1 in cells, which may contribute to the activation of ikkbeta and the transcription factor nf-kappab, as well as other pathways dependent on irak1/4. | SIGNOR-159058 |
O75626 | Q02548 | 2 | transcriptional regulation | down-regulates quantity | 0.502 | Blimp-1 binds a site on the Pax-5 promoter in vitro and in vivo and represses the Pax-5 promoter in a binding-site-dependent manner. | SIGNOR-269089 |
P16333 | P00519 | 2 | binding | down-regulates activity | 0.4 | We also show that overexpression of nck could repress the phosphorylation of cbl by abl in vivo. Studies with nck mutants suggested that the nck sh2 domain is responsible for inhibiting the activity of abl toward both cbl and nck itself, most likely by competing with the abl sh2 for tyrosine-phosphorylated binding sites | SIGNOR-109672 |
P31749 | Q8NEB9 | 0 | relocalization | up-regulates | 0.434 | One of the best characterized targets of pi3k lipid products is the protein kinase akt or protein kinase b (pkb). In quiescent cells, pkb resides in the cytosol in a low-activity conformation. Upon cellular stimulation, pkb is activated through recruitment to cellular membranes by pi3k lipid products and phosphorylation by 3h-phosphoinositide-dependent kinase-1 (pdk1). | SIGNOR-252632 |
Q96RK0 | P27361 | 0 | phosphorylation | down-regulates | 0.374 | Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)[...] These results suggest that erk phosphorylation of ser1382 and ser1409 masks the nls and prevents its binding to kpna3 | SIGNOR-169879 |
P78527 | P07948 | 0 | phosphorylation | down-regulates activity | 0.466 | The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA.|We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro. | SIGNOR-279061 |
Q8TEB7 | Q01151 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.352 | In this study, we show that GRAIL can down-modulate the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. GRAIL-mediated down-modulation of CD83 is dependent on an intact GRAIL extracellular protease-associated domain and an enzymatically active cytosolic RING domain, and proceeds via the ubiquitin-dependent 26S proteosome pathway. Ubiquitin modification of lysine residues K168 and K183, but not K192, in the cytoplasmic domain of CD83 was shown to be necessary for GRAIL-mediated degradation of CD83. | SIGNOR-271850 |
P55286 | P35222 | 2 | binding | up-regulates activity | 0.678 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265870 |
Q14765 | Q16539 | 0 | phosphorylation | up-regulates | 0.599 | 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-154787 |
Q9Y297 | Q15910 | 1 | ubiquitination | down-regulates | 0.376 | _-trcp ubiquitinates ezh2 and jak2-mediated phosphorylation on y641 directs _-trcp-mediated ezh2 degradation. | SIGNOR-204481 |
P06400 | Q00532 | 0 | phosphorylation | up-regulates activity | 0.2 | We also proved that as a downstream molecule of the P15 pathway, Rb is inhibited after CDKL1 knockdown. Rb is a well-known tumor suppressor in cell cycle regulation.28 Phosphorylation of Rb negatively regulates the cell cycle through E2F repression.29–31 However, Rb contains 13 conserved sites that are phosphorylated by the CDK–P15 complex in cycling cells and phosphorylation will cause site-specific and diverse conformational changes in the complex.32,33 Further studies need to be conducted to decipher the phosphorylated site of Rb related to CDKL1 knockdown. | SIGNOR-273863 |
Q13794 | Q00535 | 0 | phosphorylation | down-regulates | 0.356 | We show that noxa is phosphorylated on a serine residue (s(13)) in the presence of glucose. Phosphorylation promotes its cytosolic sequestration and suppresses its apoptotic function. We identify cdk5 as the noxa kinase | SIGNOR-170357 |
Q13882 | P35222 | 1 | phosphorylation | down-regulates quantity | 0.305 | PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo. | SIGNOR-278289 |
Q8IXH6 | Q9H492 | 2 | binding | up-regulates | 0.408 | Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1 | SIGNOR-182614 |
Q13526 | P01574 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | To investigate the temporal regulation of IRF3-dependent transcription by Pin1, we used a rapid-response luciferase reporter gene. Real-time reporter gene assays showed that suppression of endogenous Pin1 expression substantially prolonged both IRF3-dependent transcription and IFN-beta promoter activation after poly(I)dotpoly(C) stimulation (Fig. 4c,d). Consistent with the inhibitory effects of Pin1 on the IFN-beta promoter | SIGNOR-252289 |
O60882 | P16112 | 1 | cleavage | down-regulates quantity by destabilization | 0.477 | Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)|It has been suggested that MMPs play a role in the hydrolysis of COMP and, therefore, compromise the integrity of the cartilage ECM structure leading to the ultimate loss of joint function | SIGNOR-266981 |
Q5TEC6 | Q92830 | 0 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269599 |
Q00653 | P04637 | 2 | binding | up-regulates | 0.425 | P52 cooperates with p53 to regulate other known p53 target genes. | SIGNOR-149811 |
Q86TM6 | P23786 | 1 | ubiquitination | down-regulates quantity | 0.2 | Taken together, these data suggest that HRD1 selectively and specifically downregulates intracellular CPT2 levels.|These results demonstrate that HRD1 ubiquitinates CPT2, which is processed through Lys-48-linked ubiquitin chains. | SIGNOR-278723 |
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