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 |
|---|---|---|---|---|---|---|---|
P18089 | P63096 | 2 | binding | up-regulates activity | 0.463 | 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-256714 |
Q92633 | P09471 | 2 | binding | up-regulates activity | 0.435 | 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-256975 |
P17612 | P19838 | 1 | phosphorylation | up-regulates | 0.509 | In this study, we demonstrate that the phosphorylation of p50 and p65 by the catalytic subunit of protein kinase a (pkac) is essential for nf-kappab dna binding and transactivation activity. treatment with h89 and knockdown of pkac in cells led to the inhibition of phosphorylation at p50 ser(337) and p65 ser(276) and loss of dna binding by nf-kappab. | SIGNOR-158595 |
P04637 | P27361 | 0 | phosphorylation | up-regulates | 0.704 | Mutant p53 is constitutively phosphorylated at serine 15 in uv-induced mouse skin tumors: involvement of erk1/2 map kinase. | SIGNOR-100270 |
Q9UQM7 | Q00613 | 1 | phosphorylation | up-regulates activity | 0.513 | Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells. | SIGNOR-250631 |
P29475 | Q15139 | 0 | phosphorylation | up-regulates activity | 0.385 | In addition, we demonstrate that protein kinase D1 activates nNOS by phosphorylating the activatory residue Ser1412, leading to increased \u00b7NO production, hence establishing a novel role of PKD in the regulation of \u00b7NO synthesis.|PKD1 phosphorylates nNOS at activatory Ser 1412 in vitro and in live cells. | SIGNOR-278426 |
P00533 | Q99075 | 2 | binding | up-regulates | 0.768 | Ten growth factors and their erbb specificities are depicted: egf, amphiregulin((ar), and tgfalfa bind erbb-1, betacellulin, heparin binding egf-like growth factor, and epiregulin bing both erbb-1 and erbb-4 | SIGNOR-121977 |
P59594 | O60603 | 2 | binding | up-regulates activity | 0.2 | S protein is a ligand for human TLR2. S protein utilizes toll-like receptor 2(TLR 2) to increase IL-8 production.Our results show that SARS S protein in a soluble form increased IL-8 production through hTLR2 ligand interaction. | SIGNOR-260972 |
Q16635 | O95835 | 0 | phosphorylation | down-regulates activity | 0.387 | When the inhibitory Hippo kinase module is ' on ', LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.|When the inhibitory Hippo kinase module is \u2018on\u2019, LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off. | SIGNOR-279200 |
Q9UBE8 | Q92793 | 1 | phosphorylation | up-regulates activity | 0.557 | In vitro kinase assay showed that NLK could phosphorylate the C-terminal domain of CBP. | SIGNOR-280048 |
Q13887 | P04150 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.292 | We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα | SIGNOR-256118 |
Q13464 | Q99717 | 1 | phosphorylation | up-regulates activity | 0.306 | The results showed that SMAD5 was directly phosphorylated at Ser463/465 by ROCK1 (Fig.\u00a04g).|These data indicated that the activation of SMAD5 induced by TEM8 was mediated directly by the RhoC/ROCK1 pathway.To evaluate the effect of SMAD5 on the cellular functions of TEM8, SMAD5 was knockdown in TEM8-overexpressing cells. | SIGNOR-280107 |
P07288 | P08047 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. | SIGNOR-253664 |
Q99986 | P38432 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.361 | The active murine VRK1, but not its kinase-dead mutant (K179E), also phosphorylates coilin in Ser184 ( xref ). | SIGNOR-279772 |
Q14980 | P04350 | 2 | binding | up-regulates | 0.402 | Direct binding of numa to tubulin is mediated by a novel sequence motif in the tail domain that bundles and stabilizes microtubules. | SIGNOR-117025 |
Q15118 | P05106 | 1 | phosphorylation | down-regulates activity | 0.306 | PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3. | SIGNOR-250264 |
P35712 | P35222 | 2 | binding | down-regulates activity | 0.654 | SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. | SIGNOR-256073 |
P36896 | P84022 | 1 | phosphorylation | up-regulates activity | 0.741 | ActRIIB, and then partners with a type I receptor, either activin receptor-like kinase 4 (ALK4 or ActRIB) or ALK5 (T²RI), to induce phosphorylation of Smad2/Smad3 and activate a TGF-²-like signaling pathway | SIGNOR-235160 |
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 |
P52333 | P35222 | 1 | phosphorylation | up-regulates activity | 0.444 | Jak3 phosphorylates Tyr 30, Tyr 64, and Tyr 86 of beta-catenin in intestinal epithelial cells. | SIGNOR-278180 |
P08238 | O95433 | 2 | binding | up-regulates activity | 0.661 | The N-terminal region of Aha1 interacts with the central domain of Hsp90 and stimulates Hsp90 ATPase activity | SIGNOR-252212 |
Q07654 | Q99626 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.391 | The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. | SIGNOR-253967 |
Q15797 | O00238 | 0 | phosphorylation | up-regulates | 0.643 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-187190 |
P01106 | P11274 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.362 | In the present study we demonstrate that MYC and its partner MAX bind to the BCR promoter, leading to up-regulation of BCR and BCR/ABL1 at both transcriptional and protein levels.|Here we describe a regulatory pathway modulating BCR and BCR/ABL1 expression, showing that the BCR promoter is under the transcriptional control of the MYC/MAX heterodimer. | SIGNOR-272144 |
P42224 | P49336 | 0 | phosphorylation | up-regulates activity | 0.392 | We previously demonstrated that Mediator kinase inhibitor cortistatin A (CA) reduced proliferation of JAK2-mutant AML in vitro and in vivo and also suppressed CDK8-dependent phosphorylation of STAT1 at serine 727. Here we report that phosphorylation of STAT1 S727 promotes the proliferation of AML cells with JAK-STAT pathway activation. | SIGNOR-273179 |
Q96AC1 | Q8WUP2 | 2 | binding | up-regulates activity | 0.783 | Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration. | SIGNOR-266108 |
Q04206 | P60510 | 0 | dephosphorylation | up-regulates activity | 0.361 | Suppression of MEK/ERK signaling pathway enhances cisplatin-induced NF-kappaB activation by protein phosphatase 4-mediated NF-kappaB p65 Thr dephosphorylation | SIGNOR-248549 |
P27695 | P01266 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter. | SIGNOR-271694 |
P07766 | P16333 | 1 | relocalization | up-regulates activity | 0.372 | We present strong evidence that ligand engagement of TCR-CD3 induces a conformational change that exposes a proline-rich sequence in CD3ϵ and results in recruitment of the adaptor protein Nck. | SIGNOR-259934 |
Q99952 | O43586 | 2 | binding | up-regulates activity | 0.565 | These data confirm the importance of these residues to the binding interaction, and they suggest that much of the COOH-terminal region of PTP HSCF may be required for highest affinity binding to PST PIP.|Because this protein-protein interaction appears to be required for the dephosphorylation of PST PIP phosphotyrosines (20), it may be a potentially important new mechanism for the regulation of the cytoskeleton. | SIGNOR-262594 |
Q9Y243 | O60346 | 0 | dephosphorylation | down-regulates activity | 0.648 | 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-248330 |
Q9UPT6 | Q16584 | 2 | binding | up-regulates | 0.552 | These data demonstrate that jip3 interacts with proteins that can form a mapk signaling module, including jnk, mkk7, and mlk3jip3 increases mlk3-stimulated jnk activity. | SIGNOR-73909 |
P20645 | Q7Z6M1 | 0 | relocalization | up-regulates activity | 0.385 | P40 is a very potent transport factor in that the pure, recombinant protein can stimulate, significantly, an in vitro transport assay that measures transport of mannose 6-phosphate receptors from endosomes to the trans-Golgi network. The functional importance of p40 is confirmed by the finding that anti-p40 antibodies inhibit in vitro transport. Finally, p40 shows synergy with Rab9 in terms of its ability to stimulate mannose 6-phosphate receptor transport. These data are consistent with a model in which p40 and Rab9 act together to drive the process of transport vesicle docking. | SIGNOR-253091 |
O75444 | P42680 | 0 | phosphorylation | up-regulates activity | 0.2 | We subsequently investigated whether Tec phosphorylated c-Maf at Tyr21/92/131.|We found that overexpression of Tec enhanced the binding of c-Maf to the MARE site derived from the IL-4 promoter (XREF_FIG).|As shown in xref , tyrosine phosphorylation of c-Maf was strongly enhanced by Tec and this Tec-induced tyrosine phosphorylation was completely mitigated by Ptpn22. | SIGNOR-279433 |
P15172 | Q969P5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.56 | Here we present evidence that mafbx targets myod for degradation in several models of skeletal muscle atrophy. | SIGNOR-184861 |
P17252 | P08670 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.284 | We reported that stoichiometric phosphorylation by either cAMP-dependent protein kinase or protein kinase C induces disassembly of vimentin filaments. In the present work, we attempted to identify the sites of vimentin phosphorylated by each protein kinase. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-8, Ser-9, Ser-20, Ser-25, Ser-33, and Ser-41 were specifically phosphorylated by protein kinase C, whereas Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. | SIGNOR-248880 |
Q96LC9 | P28482 | 0 | phosphorylation | up-regulates | 0.253 | Phosphomimetic mutation of this site (s74d) moderately enhanced bmf apoptotic activity in vivo.22 here, we demonstrate a previously unrecognized mode of regulation of bmf. We show that b-raf-mek-erk2 signaling regulates bmf phosphorylation at serine 74 and serine 77. Phosphorylation of serine 77 downregulates the pro-apoptotic activity of bmf. | SIGNOR-195475 |
O95257 | Q99717 | 0 | transcriptional regulation | up-regulates quantity | 0.2 | Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation | SIGNOR-268942 |
P04049 | Q8WXI2 | 2 | binding | up-regulates | 0.767 | We show cnk2 interacts with raf. cnk2 interacts with the gef domain of rlf and with both the regulatory and catalytic domains of raf. The raf interaction was also mapped to the carboxyl-terminal half of cnk2. Overexpression of cnk2 results in inhibition of the mapk signaling pathway. | SIGNOR-119039 |
P02647 | P04180 | 2 | binding | up-regulates activity | 0.782 | Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high density lipoproteins (HDL) is essential for formation of mature (spheroidal) HDL during the antiatherogenic process of reverse cholesterol transport. After attachment of LCAT to discoidal HDL, the helix 5/5 domains in apoA-I form amphipathic presentation tunnels for migration of hydrophobic acyl chains and amphipathic UC from the bilayer to the phospholipase A2-like and esterification active sites of LCAT, respectively. | SIGNOR-252103 |
P09471 | P34972 | 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-256979 |
Q07817 | P45983 | 0 | phosphorylation | down-regulates | 0.775 | By site-directed mutagenesis studies, we have identified that serine 62 is the necessary site for taxol- or 2-me-induced bcl-xl phosphorylation in prostate cancer cells. Further studies with the inhibitor of jun kinase (jnk) and phosphorylation mutant of bcl-xl reveal the augmentative role of jnk-mediated bcl-xl phosphorylation in apoptosis of prostate cancer cells. In summary, our studies suggest that the phosphorylation of bcl-xl by stress response kinase signaling might oppose the anti-apoptotic function of bcl-xl to permit prostate cancer cells to die by apoptosis | SIGNOR-99219 |
P45983 | P31749 | 1 | phosphorylation | up-regulates activity | 0.427 | We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase. | SIGNOR-252426 |
P25054 | P35222 | 2 | binding | down-regulates quantity | 0.921 | Apc binds to both b-catenin and axin, and could shuttle b-catenin from the plasma membrane and nucleus to the cytoplasmic axin complex. APC cooperates with Axin to promote the phosphorylation of _-catenin by GSK3 [which requires priming phosphorylation by casein kinase 1, _-isoform (CK1_)]. | SIGNOR-177230 |
P50148 | P07550 | 2 | binding | up-regulates activity | 0.336 | 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-257081 |
O95999 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.468 | Upon DNA damage, ATM phosphorylates the residue T91 of BCL10, promoting binding of BCL10 to RNF8 and simultaneously presenting UBC13 to RNF8.|When cells were pre-treated with different PIKK inhibitors, the ATM specific inhibitor KU55933 efficiently reduced etoposide induced focus formation of BCL10, whereas pretreatment of cells with NU6027, an ATR specific inhibitor, or NU7026, a DNA-PKcs-specific inhibitor, did not compromise etoposide induced focus formation of BCL10 (XREF_FIG). | SIGNOR-278392 |
P06748 | P09467 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | For instance, nucleophosmin (NPM1) and zinc-finger protein X-linked (ZFX) bind to the E-box and ZFX binding site on the FBP1 promoter, respectively, and restrain FBP1 expression to facilitate aerobic glycolysis in PDAC and melanoma | SIGNOR-267594 |
Q9UNE7 | Q9UK22 | 2 | binding | up-regulates activity | 0.59 | Through this novel interaction, which is mediated by the TPR domain of CHIP and an N-terminal PEST domain of Fbx2, CHIP facilitates the ubiquitination and degradation of Fbx2-bound glycoproteins. This study highlights a novel mechanism of F-box protein-mediated ubiquitination that contributes to glycoprotein homeostasis. | SIGNOR-271589 |
P48431 | Q99986 | 0 | phosphorylation | up-regulates activity | 0.468 | VRK1, but not kinase-dead VRK1 (K179E), phosphorylated Sox2 (XREF_FIG). | SIGNOR-279578 |
Q9NR96 | P03217 | 0 | post transcriptional regulation | down-regulates quantity by destabilization | 0.2 | The EBV lytic-phase protein BGLF5 reduces TLR9 expression through mRNA degradation. We established that the EBV early protein BGLF5 degrades TLR9 mRNA in vitro, providing a mechanism for its contribution to TLR9 downregulation. | SIGNOR-266633 |
P48443 | P10276 | 2 | binding | up-regulates | 0.669 | Here we report that the transcriptional activity of rar and rxr can be reciprocally modulated by direct interactions between the two proteins | SIGNOR-16466 |
Q14653 | Q80H93 | 2 | binding | down-regulates activity | 0.2 | Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.We also found that proteins 8b and 8ab could physically interact with IRF3. This counteracting effect was partially mediated by protein 8b/8ab-induced degradation of IRF3 in a ubiquitin-proteasome-dependent manner. Taken together, we propose that SARS-CoV may exploit the unique functions of proteins 8b and 8ab as novel mechanisms to overcome the effect of IFN response during virus infection.. | SIGNOR-260240 |
P24752 | P00533 | 0 | phosphorylation | up-regulates activity | 0.2 | We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 ( xref ).|We found that purified EGFR and FGFR1 directly phosphorylate and activate ACAT1 (XREF_FIG). | SIGNOR-279996 |
Q02750 | Q5TCX8 | 0 | phosphorylation | up-regulates activity | 0.2 | These experiments showed that MEK1 is phosphorylated by MLK4 on Ser217/221 | SIGNOR-260767 |
Q9BSJ6 | Q13492 | 1 | relocalization | down-regulates | 0.2 | The cats interaction domain of calm was mapped to aa 221-335 of calm. This domain is contained in the calm/af10 fusion protein. Cats localizes to the nucleus and shows a preference for nucleoli. Expression of cats was able to markedly increase the nuclear localization of calm and of the leukemogenic fusion protein calm/af10. | SIGNOR-144680 |
Q9Y618 | O15111 | 0 | phosphorylation | down-regulates | 0.416 | Nf-kappab transcription requires ikkalpha to phosphorylate smrt on chromatin, stimulating the exchange of corepressor for coactivator complexes. Ikk directly phosphorylates smrt to stimulate nuclear export. Ikkalpha orchestrates smrt derepression, a prerequisite for nf-kappab transcription and survival. | SIGNOR-129956 |
Q9HBA0 | Q13438 | 2 | binding | up-regulates quantity by stabilization | 0.374 | Here we report that OS-9, a ubiquitously expressed endoplasmic reticulum (ER)-associated protein, interacts with the cytosolic N-terminal tail of TRPV4.Thus, OS-9 regulates the secretory transport of TRPV4 and appears to protect TRPV4 subunits from the precocious ubiquitination and ER-associated degradation. Our data suggest that OS-9 functions as an auxiliary protein for TRPV4 maturation. | SIGNOR-261064 |
O00141 | O15111 | 1 | phosphorylation | up-regulates activity | 0.26 | SGK1 directly phosphorylates IKKalpha at Thr 23 and indirectly activates IKKalpha at Ser 180.|SGK1 directly phosphorylates IKKalpha at Thr-23 and indirectly activates IKKalpha at Ser-180. | SIGNOR-278987 |
P27361 | Q93045 | 1 | phosphorylation | down-regulates activity | 0.352 | SCG10, a growth cone-enriched MT-destabilizing protein, has been recently characterized as an in vitro substrate for various serine/threonine kinases including PKA, MAP kinase, and CDK (19). We have found that SCG10 is phosphorylated in vivo in developing rat brain.| The sites for MAP kinase phosphorylation were identified as Ser-62 and Ser-73 of SCG10|By expressing a series of phosphorylation site mutants, we showed that the MT-destabilizing effect of SCG10 could be modulated. While the nonphosphorylatable mutant showed higher activity than the wild-type protein, the activity of the mutant in which phosphorylation on all four sites was mimicked by an aspartate residue was greatly reduced. These data suggest that the nonphosphorylated state of SCG10 represents the most active form of the protein. | SIGNOR-249115 |
Q8WV16 | Q96CV9 | 2 | binding | up-regulates activity | 0.2 | DCAF4-mediated ubiquitination of OPTN facilitates the degradation of DBR-exposed SOD1. OPTN is involved in degradation of DBR-exposed SOD1. These data demonstrate that DCAF4-including CRL4 complex mediates OPTN ubiquitination at lysine 501, and this ubiquitination is absent in the ALS-related OPTNmut. | SIGNOR-272210 |
P60953 | P98170 | 0 | ubiquitination | down-regulates quantity | 0.398 | As XIAP can directly ubiquitinate Cdc42, we tested if the RING domain of XIAP is required for modulating the protein levels of Cdc42 in vivo .|We then investigated the molecular mechanisms behind XIAP mediated Cdc42 degradation. | SIGNOR-278799 |
Q15139 | P12931 | 0 | phosphorylation | up-regulates | 0.411 | Critical for the regulation of pkd1 activity in response to oxidative stress are src- and abl-mediated tyrosine phosphorylations that eventually lead to protein kinase cdelta (pkcdelta)-mediated activation of pkd1. our data suggest that pkd1 phosphorylation at tyr95 generates a binding motif for pkcdelta, and that oxidative stress-mediated pkcdelta/pkd interaction results in pkd1 activation loop phosphorylation and activation. | SIGNOR-157716 |
O15198 | P36894 | 0 | phosphorylation | up-regulates activity | 0.706 | To ascertain whether overexpression of BMPr1A can initiate adipocyte lineage commitment in the absence of its BMP ligand, constitutively active (CA)-BMPr1A and CA-BMPr1B were expressed in C3H10T1/2 stem cells using a mouse stem cell virus (MSCV) retroviral system. […]Thus, their overexpression provoked a substantial rise in the phosphorylation of Smad1/5/8 and p38 MAPK, known downstream phosphorylated intermediates in the BMP signaling pathway. | SIGNOR-255772 |
P07288 | Q9NY61 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. | SIGNOR-253669 |
Q5VT97 | P63000 | 1 | gtpase-activating protein | down-regulates activity | 0.402 | 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-260522 |
P06493 | Q9Y5T5 | 1 | phosphorylation | up-regulates | 0.455 | Here, we report that cyclin-dependent kinase 1 (cdk1) phosphorylates the histone h2a deubiquitinase ubp-m at serine 552 (s552p), and, importantly, this phosphorylation is required for cell cycle progression. | SIGNOR-202678 |
Q9Y6D9 | P61244 | 2 | binding | up-regulates activity | 0.301 | the role MAX plays in transcription is thought to be primarily as a cofactor for DNA binding. In this capacity, however, it appears to be essential for most, if not all, the known biological activities of MYC. MAX also functions as a cofactor for DNA binding for a group of bHLHZip proteins related to MYC, including MNT, MXD1-4 (formerly Mad1, Mxi1, Mad3 and Mad4), and MGA. Like MYC, these proteins do not homodimerize and appear to be incapable of binding DNA on their own, but when bound to MAX, they recognize E-box sequences. | SIGNOR-240357 |
P68400 | Q9Y4R8 | 1 | phosphorylation | down-regulates | 0.2 | Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1. ere, we show that tel2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (ck2) | SIGNOR-200202 |
P05771 | Q13224 | 1 | phosphorylation | up-regulates activity | 0.364 | These results indicate that PKC can directly phosphorylate S1303 and S1323 in the NR2B C terminus, leading to enhanced currents through NMDA receptor channels. | SIGNOR-249087 |
P0DP25 | O43303 | 2 | binding | up-regulates activity | 0.328 | We report that CP110 interacts with two different Ca2+-binding proteins, calmodulin (CaM) and centrin, in vivo. our data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. | SIGNOR-266348 |
P30304 | Q00534 | 1 | dephosphorylation | up-regulates activity | 0.704 | Invalidation of CDK4 has no impact by itself on the cell proliferation, but invalidation of CDC25A prevents the dephosphorylation of CDK6 (Y24) and CDK4 (Y17) residues, and impedes their association with CCNDs. | SIGNOR-267569 |
P25963 | P68400 | 0 | phosphorylation | down-regulates | 0.581 | Casein kinase ii phosphorylates i kappa b alpha at s-283, s-289, s-293, and t-291 and is required for its degradation. | SIGNOR-40502 |
Q12809 | P05556 | 2 | binding | up-regulates activity | 0.2 | One such mechanism is operant in colorectal cancer (CRC) cells. On integrin-dependent CRC cell adhesion, the Kv11.1/β1 integrin complex recruits the PI3K p85 subunit, which stimulates AKT phosphorylation and thus regulates autophagy | SIGNOR-277613 |
O60674 | P38484 | 2 | binding | up-regulates activity | 0.7 | In the classical model of IFNgamma signaling, dimeric IFNgamma cross-links the IFNGR1 receptor subunit that results in allosteric changes in receptor cytoplasmic domain. This results in movement of JAK2 from receptor subunit IFNGR2 to IFNGR1. The JAKs autophosphorylate and then phosphorylate IFNGR1 cytoplasmic domain. This results in binding, phosphorylation, and dimer formation of STAT1_. The dimeric STAT1_ dissociates from receptor and undergoes nuclear translocation via an intrinsic NLS for specific gene activation | SIGNOR-249489 |
P36507 | P41279 | 0 | phosphorylation | up-regulates | 0.436 | Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases. | SIGNOR-129694 |
P10398 | P01112 | 2 | binding | up-regulates | 0.838 | The raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases. | SIGNOR-175183 |
P42685 | P00533 | 1 | phosphorylation | down-regulates activity | 0.409 | Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants. | SIGNOR-279177 |
Q96AP0 | O76064 | 0 | polyubiquitination | up-regulates quantity by stabilization | 0.2 | The Rnf8 RING-finger domain is essential for Tpp1 stability and retention at telomeres. Rnf8 physically interacts with Tpp1 to generate Ubc13-dependent Lys63 polyubiquitin chains that stabilize Tpp1 at telomeres. The conserved Tpp1 residue Lys233 is important for Rnf8-mediated Tpp1 ubiquitylation and localization to telomeres. | SIGNOR-272722 |
P00533 | P30530 | 2 | phosphorylation | up-regulates activity | 0.43 | In this study, we have identified for the first time a direct interaction between EGFR and Axl RTKs, with EGF and EGFR induced activation of Axl as a novel signalling pathway to invasion in cancer cells.|The activation of Axl was shown to occur through direct phosphorylation by EGFR of Axl tyrosine 779, one of the key residues within Axl that serves as a multi-substrate docking site for further downstream signalling. | SIGNOR-279734 |
P11309 | P31269 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Thus Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells. | SIGNOR-261632 |
P05019 | Q9UBK2 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.34 | PGC-1 alpha specifically induces IGF1 and represses myostatin, and expression of PGC-1a 4 in vitro and in vivo induces robust skeletal muscle hypertrophy | SIGNOR-256152 |
Q08334 | P29597 | 2 | binding | up-regulates | 0.648 | Specifically, il-10 effects the activation of jak1 (associated with the il-10 receptor ? Chain) and tyk2 (associated with the il-10 receptor ? Chain) and induces the activation of stat1, stat3, and, in some cells, stat5. | SIGNOR-68013 |
P04198 | Q7Z6Z7 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.423 | HUWE1 ubiquitinates and directs MYCN degradation to the proteasome. | SIGNOR-278750 |
P20226 | O14981 | 2 | binding | up-regulates activity | 0.707 | We present evidence that the NC2alpha subunit interacts with BTAF1. Addition of NC2alpha or the NC2 complex can stimulate the ability of BTAF1 to interact with TBP. | SIGNOR-263919 |
Q96A00 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.549 | Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ilk predominantly phosphorylated the site critical for potent inhibition, i.e. Thr(38) of cpi-17 | SIGNOR-90828 |
P26992 | P26441 | 2 | binding | up-regulates | 0.791 | Ciliary neurotrophic factor (cntf) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, cntfr, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (lifr) | SIGNOR-81379 |
P53350 | P13693 | 1 | phosphorylation | down-regulates | 0.716 | Plk phosphorylates tctp on two serine residues. These results suggest that phosphorylation decreases the microtubule-stabilizing activity of tctp and promotes the increase in microtubule dynamics that occurs after metaphase | SIGNOR-91348 |
P09471 | P29274 | 2 | binding | up-regulates activity | 0.301 | 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-257239 |
P19838 | O15111 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.747 | All residues of p105 phosphorylated by ikka are c-terminal; the major phosphorylation region contains three serines (ser923; ser927;ser932) and two threonines (thr927 and thr391). | SIGNOR-70449 |
P08908 | Q5T0F9 | 0 | 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 |
Q8IX03 | Q15418 | 0 | phosphorylation | up-regulates | 0.335 | Moreover, we found that rsk1/2 specifically phosphorylates kibra at two highly conserved sites (thr(929) and ser(947)) in vitro and in cells. Rsk-mediated phosphorylation is required for kibra binding to rsk1, but not rsk2. | SIGNOR-203298 |
P42685 | P60484 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.599 | Rak phosphorylates PTEN on Tyr 336 to prevent its protein degradation. In this study, we demonstrate that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr336. Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation. | SIGNOR-275458 |
Q05655 | P09758 | 1 | phosphorylation | down-regulates activity | 0.2 | Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation. | SIGNOR-273820 |
Q13370 | Q14164 | 0 | phosphorylation | up-regulates activity | 0.2 | While IKK\u03b5 phosphorylates and activates PDE3B to induce catecholamine resistance, TBK1 inhibits AMPK activity to reduce catabolism via this pathway. | SIGNOR-278517 |
P63279 | P35712 | 1 | sumoylation | down-regulates activity | 0.367 | We show that SOX6 is modified in vitro and in vivo by small ubiquitin‐related modifier (SUMO) on two distinct sites. Mutation of both sites abolished SOX6 sumoylation and increased SOX6 transcriptional activity. SUMO dependent repression of SOX6 transcription was promoted by UBC9 whereas siRNA to UBC9, cotransfection of inactive UBC9 or a SUMO protease increased SOX6 transcriptional activity. | SIGNOR-256130 |
P61586 | Q9H8V3 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.712 | 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-260550 |
Q13214 | O14786 | 2 | binding | up-regulates activity | 0.753 | Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction. | SIGNOR-261814 |
P61073 | P08754 | 2 | binding | up-regulates activity | 0.478 | Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner | SIGNOR-278104 |
P01589 | P60568 | 2 | binding | up-regulates | 0.927 | Il-2 is a cytokine that functions as a growth factor and central regulator in the immune system and mediates its effects through ligand-induced hetero-trimerization of the receptor subunits il-2r alpha, il-2r beta, and gamma(c). | SIGNOR-144537 |
Q9H3C7 | P03372 | 2 | binding | down-regulates activity | 0.2 | We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells. | SIGNOR-269076 |
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