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 |
|---|---|---|---|---|---|---|---|
P69905 | P00738 | 0 | binding | down-regulates quantity | 0.738 | Haptoglobin forms a complex of extremely high affinity with Hb via a well-characterized globin site. Our results show that upon Hb-haptoglobin binding, the globin radical, loses its ability to be terminated by forming globin dimers. | SIGNOR-251816 |
P16112 | P08254 | 0 | cleavage | down-regulates quantity by destabilization | 0.738 | Aggrecan Degradation in Human Cartilage Evidence for both Matrix Metalloproteinase and Aggrecanase Activity in Normal, Osteoarthritic, and Rheumatoid Joints|Stromelysin-1 (MMP-3), as well as other MMPs, cleave aggrecan in the interglobular domain between Asn341 and Phe342 to generate a G1 fragment with the COOH terminus VDIPEN341 (11–13). This fragment has been isolated and identified by NH2-terminal sequence analysis from human OA cartilage (11). A second proteolytic activity identified as “aggrecanase” also cleaves aggrecan in the interglobular domain, but between Glu373 and Ala374 (19–24), generating a G1 fragment with a COOH terminus of NITEGE374 | SIGNOR-266986 |
O75581 | Q13467 | 0 | binding | up-regulates activity | 0.738 | Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. | SIGNOR-258966 |
P30518 | P01185 | 0 | binding | up-regulates | 0.738 | We report here the cloning of a complementary dna encoding the hepatic v1a arginine vasopressin receptor. The liver cdna encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin. | SIGNOR-20185 |
Q9Y243 | P67775 | 0 | dephosphorylation | down-regulates activity | 0.738 | Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes | SIGNOR-248654 |
Q14186 | Q14209 | 0 | binding | up-regulates activity | 0.738 | The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family.In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3. | SIGNOR-240550 |
P02649 | P02647 | 0 | relocalization | up-regulates activity | 0.738 | ApoA-I stimulates apoE secretion in mature human adipocytes. The regulation of apoE secretion by apoA-I, is neither dependent upon an increase in gene transcription, nor upon increased release from the Golgi. It may therefore be assumed that, in macrophage models, apoE is stored mainly in the cytoplasm and/or on the cell surface, with apoA-I enabling secretion of this cytoplasmic pool | SIGNOR-252105 |
P12931 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.738 | Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl mediated Src degradation.|Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation | SIGNOR-278539 |
Q9ULV1 | P41221 | 0 | binding | up-regulates activity | 0.738 | We show that in addition to its inhibitory function, Wnt5a can also activate beta-catenin signaling in the presence of the appropriate Frizzled receptor, Frizzled 4. | SIGNOR-258954 |
P42224 | P00533 | 0 | phosphorylation | up-regulates | 0.738 | The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation | SIGNOR-235689 |
P11912 | P07948 | 0 | phosphorylation | up-regulates activity | 0.738 | Y182 of CD79a appears to be the initial and preferred site of Ag receptor phosphorylation by Src family kinases. In vitro, Src family Lyn and Fyn predominantly phosphorylate this residue in CD79a, and Y195 does so in CD79b. phosphorylation of Y182 alone can lead to further kinase activation and/or effector focusing necessary for phosphorylation of certain downstream targets, such as p62, p110, and Shc, but not others, such as Vav. | SIGNOR-251397 |
Q13950 | P84022 | 0 | binding | down-regulates activity | 0.738 | Tgf-beta inhibited the expression of the cbfa1 and osteocalcin genes, whose expression is controlled by cbfa1 in osteoblast-like cell lines. This inhibition was mediated by smad3, which interacts physically with cbfa1 and represses its transcriptional activity at the cbfa1-binding ose2 promoter sequence. | SIGNOR-235902 |
O60500 | P06241 | 0 | phosphorylation | up-regulates activity | 0.738 | Fyn directly bound Nephrin via its SH3 domain, and Fyn directly phosphorylated Nephrin.|Similar to Fyn deletion, simultaneous deletion of Fyn and Yes reduced Nephrin phosphorylating activity. | SIGNOR-279523 |
P56159 | Q99748 | 0 | binding | up-regulates | 0.738 | A receptor complex comprised of trnr1 (gdnfr alpha) and ret was recently identified and found to be capable of mediating both gdnf and ntn signaling | SIGNOR-49119 |
P12757 | Q9HAU4 | 0 | ubiquitination | down-regulates activity | 0.738 | Tgf-beta also induces the association of smurf2 with the transcriptional co-repressor snon and we show that smad2 can function to mediate this interaction. This allows smurf2 hect domain to target snon for ubiquitin-mediated degradation by the proteasome. | SIGNOR-236090 |
Q01484 | Q92823 | 0 | relocalization | up-regulates quantity | 0.737 | Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains. | SIGNOR-266719 |
O60216 | P53350 | 0 | dephosphorylation | down-regulates quantity by destabilization | 0.737 | We suspected that the observed enhancement of Scc1's cleavability in the presence of Plk1 might be due to phosphorylation at two sites that are directly adjacent to the cleavage sites, Ser175 and Ser454, which we had found to be phosphorylated in mitosis in vivo (Table 1). We therefore mutated these two residues to alanine, thereby creating mutant Scc1-S175A/S454A (see Figure 1C), and tested the cleavability of this mutant in the absence or presence of Plk1 in vitro. |Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase. | SIGNOR-275535 |
Q99683 | Q12933 | 0 | binding | up-regulates activity | 0.737 | Traf2 is a strong activator of ask1 | SIGNOR-60747 |
Q14626 | P20809 | 0 | binding | up-regulates | 0.737 | Il-11 has been shown to induce gp130-dependent signaling through the formation of a high affinity complex with the il-11 receptor (il-11r) and gp130 | SIGNOR-81102 |
P62993 | Q06124 | 0 | binding | up-regulates activity | 0.737 | SHP-2 is thus a positive regulator of ERK by leptin receptors, and both the adaptor function and the phosphatase activity of SHP-2 are critical for this regulation. Based on these data, we conclude that tyrosinephosphorylation of SHP-2 is a mediator of ERK activation viaTyr-985. This is likely to occur via Grb-2 binding to SHP-2 atthe C terminus followed by activation of the Ras-Raf pathwayas suggested for other signaling systems (55, 56) and morerecently for the leptin receptor (33). | SIGNOR-263498 |
Q8N3U4 | P53350 | 0 | dephosphorylation | down-regulates activity | 0.737 | Two phosphorylation sites in Scc1 (Thr144 and Thr312) match the consensus proposed by Nakajima et al. [24]. These two sites, in addition to one in Scc1 (Ser454) and three in SA2 (Thr1109, Ser1137, and Ser1224) conform with the consensus proposed by Barr et al. [25]. These findings are consistent with the possibility that at least some of the sites in Scc1 and SA2 are directly phosphorylated by Plk1.|Phosphorylation of SA2 Is Essential for the Dissociation of Cohesin from Chromosomes during Prophase and Prometaphase | SIGNOR-275534 |
P43405 | P29350 | 0 | dephosphorylation | down-regulates | 0.737 | We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene. | SIGNOR-70234 |
P00533 | Q96JA1 | 0 | binding | down-regulates | 0.736 | Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiquitin ligase that simultaneously ubiquitylates egfr and lrig1 and sorts them for degradation | SIGNOR-127304 |
P19022 | O60716 | 0 | binding | up-regulates quantity by stabilization | 0.736 | To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member. | SIGNOR-252125 |
O15105 | Q6ZNA4 | 0 | ubiquitination | down-regulates | 0.736 | Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia | SIGNOR-119666 |
Q9NYZ3 | P53350 | 0 | phosphorylation | up-regulates | 0.736 | In this study, we show that g2 and s-phase-expressed 1 (gtse1) protein, a negative regulator of p53, is required for g2 checkpoint recovery and that plk1 phosphorylation of gtse1 at ser 435 promotes its nuclear localization, and thus shuttles p53 out of the nucleus to lead to its degradation during the recovery. | SIGNOR-166417 |
P17542 | P25800 | 0 | binding | up-regulates | 0.736 | Transcriptional activity of tal1 in t cell acute lymphoblastic leukemia (t-all) requires rbtn1 or -2 | SIGNOR-46114 |
P01106 | Q13309 | 0 | ubiquitination | down-regulates quantity | 0.736 | The F-box protein Skp2 mediates c-Myc ubiquitylation by binding to the MB2 domain | SIGNOR-243548 |
O00418 | P23443 | 0 | phosphorylation | down-regulates activity | 0.736 | We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity | SIGNOR-109712 |
Q99717 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.736 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-193378 |
P84022 | Q09472 | 0 | acetylation | up-regulates quantity by stabilization | 0.736 | Smad proteins are crucial for the intracellular signaling of transforming growth factor-beta (TGF-beta). Upon their receptor-induced activation, Smad proteins are phosphorylated and translocated to the nucleus to activate the transcription of a select set of target genes. Here, we show that the co-activator p300/CBP bound and acetylated Smad3 as well as Smad2 in vivo, and that the acetylation was stimulated by TGF-beta.A major acetylation site of Smad3 by p300/CBP is Lys-378 in the MH2 domain (Smad3C) known to be critical for the regulation of transcriptional activity. | SIGNOR-260431 |
P49841 | Q9Y243 | 0 | phosphorylation | down-regulates activity | 0.736 | Active AKT, a common mediator of cell survival signals induced by radiation through multiple intracellular signaling pathways,11, 12 suppresses apoptosis. AKT positively regulates cyclin D1 expression through inactivation of glycogen synthase kinase 3_ (GSK3_). The AKT-mediated phosphorylation of glycogen synthase kinase 3_ on serine9 decreases its kinase activity for Thr286 of cyclin D1, which inhibits the nuclear export and the cytoplasmic proteasomal degradation of cyclin D1 | SIGNOR-245424 |
P29475 | P78352 | 0 | binding | up-regulates activity | 0.736 | Neuronal NOS, a Ca2+-activated form of NOS, can bind to PSD-95 through a class III PDZ domain interaction in which its own amino-terminal PDZ domain binds to a PDZ domain of PSD-95. PSD-95 may concentrate nNOS near the NMDA receptor at postsynaptic sites in these neurons. | SIGNOR-264227 |
P29353 | P08069 | 0 | binding | up-regulates activity | 0.736 | In our present work, we show that both IRS-1 and SHC interact directly with the juxtamembrane region of the IGFIR in a phosphotyrosine-dependent manner. |We propose a model in which IGFIR autophosphorylation of Tyr-950 forms a direct binding site for the amino-terminal receptor binding domains of SHC and IRS-1. This interaction is presumed to facilitate tyrosine phosphorylation of SHC on Tyr-317 leading to GRB2/SOS interaction | SIGNOR-262587 |
Q96BD8 | Q96GD4 | 0 | phosphorylation | up-regulates activity | 0.736 | Aurora B directly phosphorylated Ska1 and Ska3 in vitro, and expression of phosphomimetic mutants of Ska1 and Ska3 impaired Ska KT recruitment and formation of stable KT-MT fibers (K-fibers), disrupting mitotic progression. We propose that Aurora B phosphorylation antagonizes the interaction between the Ska complex and the KMN network, thereby controlling Ska recruitment to KTs and stabilization of KT-MT attachments. | SIGNOR-262662 |
Q07812 | Q07820 | 0 | binding | down-regulates | 0.736 | Which of the multiple pro-survival proteins that can bind Bax (fig. S15A) can functionally restrain it? Mcl-1 must, because neutralizing Mcl-1 by enforced Noxa expression rendered MEFs containing only Bax (Bak KO cells) sensitive to the Bad BH3 mimetic ABT-737 (Fig. 4A), which inactivates Bcl-2, Bcl-xL, and Bcl-w | SIGNOR-151787 |
O15151 | Q13315 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.735 | Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm. | SIGNOR-149296 |
Q9Y4D1 | O14640 | 0 | binding | up-regulates activity | 0.735 | B-catenin-independent wnt signaling can activate rho family gtpases through at least two mechanisms: (1) direct activation of rac1 by dvl;and (2) activation of rhoa via dvl-associated activator of morphogenesis-1 (daam1), possibly through the weak-similarity guaninenucleotide exchange factor (wgef)1. | SIGNOR-185271 |
P41091 | Q9NR50 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269136 |
P62987 | Q93009 | 0 | cleavage | up-regulates quantity | 0.735 | Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors. | SIGNOR-270823 |
P40763 | P17706 | 0 | dephosphorylation | down-regulates | 0.735 | The nuclear isoform of protein-tyrosine phosphatase tc-ptp regulates interleukin-6-mediated signaling pathway through stat3 dephosphorylation. | SIGNOR-90818 |
P04150 | P07900 | 0 | binding | down-regulates | 0.735 | We report the crucial underlying role of the intranuclear heat shock protein 90 molecular chaperone complex in pulsatile GR regulation. Pharmacological interference of heat shock protein 90 (HSP90) with geldanamycin during the intranuclear chaperone cycle completely ablated GR's cyclical activity, cyclical cAMP response element-binding protein (CREB) binding protein (CBP)/p300 recruitment, and the associated cyclical acetylation at the promoter region. | SIGNOR-251667 |
P04233 | P14174 | 0 | binding | up-regulates | 0.735 | Mif binds to the extracellular domain of cd74, and cd74 is required for mif-induced activation of the extracellular signal-regulated kinase-1/2 map kinase cascade, cell proliferation, and pge2 production. | SIGNOR-101526 |
P50552 | Q13976 | 0 | phosphorylation | down-regulates activity | 0.735 | Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts | SIGNOR-268289 |
P49736 | P24941 | 0 | phosphorylation | up-regulates | 0.735 | In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2 | SIGNOR-144000 |
P20339 | Q96Q42 | 0 | binding | up-regulates activity | 0.735 | ALS2 activates Rab5 on macropinosomes. Rab5 is activated and concurrently recruited to macropinosomes during ruffle closure. ALS2 depletion abolishes transient Rab5 activation on macropinosomes, while ALS2 is recruited to macropinosomes simultaneously with Rab5 activation. Thus, we conclude ALS2 activates Rab5 on macropinosomes. | SIGNOR-277776 |
P41091 | Q13144 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269133 |
P63000 | Q14185 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.735 | We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth. | SIGNOR-266822 |
P01106 | P28482 | 0 | phosphorylation | up-regulates activity | 0.735 | Transactivation of gene expression by myc is inhibited by mutation at the phosphorylation sites thr-58 and ser-62. | SIGNOR-235700 |
Q12879 | P06241 | 0 | phosphorylation | up-regulates activity | 0.734 | To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain. | SIGNOR-247151 |
Q13464 | P42574 | 0 | cleavage | up-regulates | 0.734 | Rock i is cleaved by casp3 at a conserved detd1113/g sequence and its carboxy-terminal inhibitory domain is removed, resulting in deregulated and constitutive kinase activity. | SIGNOR-106546 |
P46937 | Q4VCS5 | 0 | relocalization | down-regulates | 0.734 | Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms. | SIGNOR-175779 |
P42224 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.734 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-133279 |
Q12933 | Q92844 | 0 | binding | down-regulates activity | 0.734 | IKK-i phosphorylates I-TRAF. In vitro kinase assays demonstrate that IKK‐i phosphorylates I‐TRAF in the middle portion that associates with TRAF2. Interestingly, TRAF2 is freed from the I‐TRAF/TRAF2 complex after I‐TRAF phosphorylation. TRAF2 isdistributed throughout the cytoplasm, in the formof inactive an I-TRAF/TRAF2 complex | SIGNOR-262714 |
Q16581 | P01024 | 0 | binding | up-regulates activity | 0.734 | A cDNA clone encoding the human C3a anaphylatoxin receptor (C3aR) was isolated from a pcDNAI/Amp expression library prepared from U-937 cells|The cDNA clone contained an insert of 4.3 kbp and was able to confer to transfected human HEK-293 cells the capacity to bind specifically iodinated human C3a. | SIGNOR-263451 |
O60469 | O95631 | 0 | binding | up-regulates activity | 0.734 | Here, we report that the Down's syndrome Cell Adhesion Molecule (DSCAM), a candidate gene implicated in the mental retardation phenotype of Down's syndrome, is expressed on spinal commissural axons, binds netrin-1, and is necessary for commissural axons to grow toward and across the midline. DSCAM and DCC can each mediate a turning response of these neurons to netrin-1. | SIGNOR-268376 |
O00311 | O14757 | 0 | phosphorylation | up-regulates | 0.734 | Chk1 directly phosphorylates essential s-phase kinases cdc7. | SIGNOR-163161 |
Q05397 | P46108 | 0 | phosphorylation | up-regulates activity | 0.733 | Tyrosine phosphorylation FAK was strictly dependent upon c-Crk II expression | Crk-inducible FAK tyrosine phosphorylation was completely abrogated by co-expression with R38K Crk (lane 2), and decreased by co-expression with W170K Crk (lane 3), indicating that the SH2 domain of c-Crk is absolutely essential for this effect. In contrast, mutants in the C-terminus of Crk that include Y222F c-Crk, which abrogates the c-Abl phosphorylation site, and W276K Crk, which mutates the C-terminal SH3 domain, modestly increased FAK activation compared to wild-type c-Crk II. | SIGNOR-250777 |
Q13546 | Q8IUC6 | 0 | binding | up-regulates activity | 0.733 | TRIF also recruits the adaptor RIP1 through the distinct RIP homotypic interaction motif. RIP1 undergoes K63-linked polyubiquitination after stimulation by TLR3 agonists, and this modification is required for NF-_B activation. | SIGNOR-216313 |
P15336 | P28482 | 0 | phosphorylation | up-regulates | 0.733 | Here, we show that in fibroblasts, insulin, epidermal growth factor (egf) and serum activate atf2 via a so far unknown two-step mechanism involving two distinct ras effector pathways: the raf-mek-erk pathway induces phosphorylation of atf2 thr71, whereas subsequent atf2 thr69 phosphorylation requires the ral-ralgds-src-p38 pathway. | SIGNOR-90517 |
P51692 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.733 | In the previous study, we demonstrated that the nuclear isoform of T-cell protein-tyrosine phosphatase (TC-PTP) dephosphorylated and deactivated signal transducer and activator of transcription 5a (STAT5a) and STAT5b, thereby negatively regulating prolactin (PRL)-mediated signaling pathway. | SIGNOR-277126 |
P36507 | P04049 | 0 | phosphorylation | up-regulates | 0.733 | To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. | SIGNOR-36553 |
Q676U5 | Q9Y4P8 | 0 | binding | up-regulates quantity | 0.733 | WIPI1 assists WIPI2 in recruiting ATG16L for LC3 lipidation. WIPI1-WIPI2 heterodimer may function more efficiently in ATG16L complex recruitment. | SIGNOR-268478 |
Q86XR7 | O00206 | 0 | binding | up-regulates | 0.733 | Mappit analysis of early toll-like receptor signalling events. | SIGNOR-160424 |
P42229 | P17706 | 0 | dephosphorylation | down-regulates activity | 0.733 | Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5. | SIGNOR-133547 |
P08581 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.732 | Tyrosine y1001, which when phosphorylated upon met activation, is involved in cbl recruitment, allowing receptor ubiquitination and down regulation | SIGNOR-185680 |
P08559 | Q9P0J1 | 0 | dephosphorylation | up-regulates activity | 0.732 | Sites 1, 2, and 3 were dephosphorylated either individually or in the presence of the other sites by the phospho-E1-phosphatase resulting in complete reactivation of the E1. The rates of dephosphorylation and reactivation were similar for sites 1, 2, and 3, indicating a random dephosphorylation mechanism | SIGNOR-252055 |
O14746 | P31749 | 0 | phosphorylation | up-regulates | 0.732 | Akt kinase enhances human telomerase activity through phosphorylation of htert subunit as one of its substrate proteins. | SIGNOR-67313 |
Q15797 | P36894 | 0 | phosphorylation | up-regulates activity | 0.732 | 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-255263 |
P31751 | O15530 | 0 | phosphorylation | up-regulates activity | 0.732 | Akt1 and akt2 are phosphorylated and activated by the protein kinase pdk1 at thr-308 or thr-309, respectively, in the activation t-loop, and further activation occurs through phosphorylation at ser-473 or ser-474, respectively. Pdk1 phosphorylates akt-2 at thr 309 in the catalytic domain, leading to enzymatic activation. | SIGNOR-134485 |
P29353 | P06241 | 0 | phosphorylation | up-regulates | 0.732 | Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2. | SIGNOR-59623 |
Q13564 | P05067 | 0 | binding | up-regulates activity | 0.732 | Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis. | SIGNOR-251577 |
P05556 | O14713 | 0 | binding | down-regulates activity | 0.732 | 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-257638 |
Q92985 | Q9Y4K3 | 0 | ubiquitination | up-regulates activity | 0.732 | We have shown that TRAF6 E3 ligase promotes IRF7 K63-linked ubiquitination that is required for EBV LMP1 activation of IRF7 [ xref ]; however, A20, a member with both E3 ligase and deubiquitinase activities in the OTU family, inhibits LMP1-stimulated IRF7 activity by acting as a deubiquitinase [ xref ]. | SIGNOR-278788 |
P29353 | Q16288 | 0 | binding | up-regulates | 0.732 | We demonstrate that the phosphotyrosine binding domain of frs-2 directly binds the trk receptors at the same phosphotyrosine residue that binds the signaling adapter shc, suggesting a model in which competitive binding between frs-2 and shc regulates differentiation versus proliferation. | SIGNOR-65958 |
P23528 | Q76I76 | 0 | dephosphorylation | up-regulates activity | 0.732 | Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH). | SIGNOR-248733 |
P23458 | O14543 | 0 | binding | down-regulates activity | 0.732 | SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition | SIGNOR-253051 |
P04637 | Q00535 | 0 | phosphorylation | up-regulates | 0.732 | We show that cdk5 phosphorylates p53 on ser15, ser33 and ser46 cdk5-stabilized p53 protein is transcriptionally active | SIGNOR-156422 |
P23458 | O15524 | 0 | binding | down-regulates | 0.732 | Socs1 and socs3 target jak1 and gp130, respectively, near the plasma membrane to prevent cytoplasmic stats from being activated, whereas pias1 principally targets activated stat1 in the cell nucleus and prevents it from binding to dna. | SIGNOR-202042 |
P22455 | P10767 | 0 | binding | up-regulates | 0.732 | Our results establish an fgf binding profile for fgfr-4 with afgf having the highest affinity, followed by k-fgf/hst-1 and bfgf. In addition, fgf-6 was found to bind to fgfr-4 in ligand competition experiments. Ligands binding to fgfr-4 induced receptor autophosphorylation and phosphorylation of a set of cellular polypeptides. | SIGNOR-18570 |
P31431 | P17252 | 0 | phosphorylation | up-regulates activity | 0.732 | The phosphorylation state of Ser(183) in the cytoplasmic tail of syndecan-4 determines the binding affinity of the cytoplasmic tail to phosphatidylinositol 4,5-bisphosphate (PIP(2)), the capacity of the tail to multimerize, and its ability to activate protein kinase C (PKC) alpha. We sought to identify the kinase responsible for this phosphorylation and to determine its downstream effects on PKCalpha activity and on endothelial cell function. Among several PKC isoenzymes tested, only PKCalpha and -delta were able to specifically phosphorylate Ser(183) in vitro. However, studies in cultured endothelial cells showed that the phosphorylation level of syndecan-4 was significantly reduced in endothelial cells expressing a dominant negative (DN) PKCdelta but not a DN PKCalpha mutant. | SIGNOR-249149 |
P15311 | Q13464 | 0 | phosphorylation | up-regulates | 0.732 | Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide | SIGNOR-185567 |
O43768 | Q96GX5 | 0 | phosphorylation | up-regulates activity | 0.732 | We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. | SIGNOR-243690 |
O15105 | Q9H0M0 | 0 | relocalization | up-regulates activity | 0.731 | We found that WWP1 inhibited transcriptional activities induced by TGF-beta. Similar to Smurfs, WWP1 associated with Smad7 and induced its nuclear export, and enhanced binding of Smad7 to TGF-beta type I receptor to cause ubiquitination and degradation of the receptor. | SIGNOR-126578 |
O43521 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.731 | In vitro, bimel was phosphorylated by extracellular signal-regulated kinase on ser(69), which resides in the bimel-specific insert region. Using phosphospecific antibody against this site, we show that this residue is actually phosphorylated in cells. We also show that phosphorylation of ser(69) promotes ubiquitination of bimel. We conclude that mek inhibitors sensitize mda-mb231 and hbc4 cells to anoikis by blocking phosphorylation and hence degradation of bimel | SIGNOR-129878 |
P40763 | Q9Y6X2 | 0 | sumoylation | down-regulates | 0.731 | Stat3 mediated signaling pathways can be inhibited by pias3 (protein inhibitor of activated stat3), which was recently found to regulate protein stability and function by its sumo (small-ubiquitin like modifiers) ligase activity in promoting sumoylation of important nuclear proteins. | SIGNOR-124723 |
P30307 | Q9H4B4 | 0 | phosphorylation | up-regulates | 0.731 | Cdc25c phosphorylation on serine 191 by plk3 promotes its nuclear translocation | SIGNOR-122090 |
P06753 | P28289 | 0 | binding | down-regulates activity | 0.731 | Tropomodulin is a 40.6-kDa protein that binds to one end of the rod-like tropomyosin and inhibits its cooperativity and binding to actin. [.] we demonstrate that it is the N-terminus of tropomyosin that interacts with tropomodulin. Among several tropomyosin isoforms tested, hTM5 encoded by the human gamma-tropomyosin gene has the highest affinity toward human erythrocyte tropomodulin. | SIGNOR-259111 |
Q05397 | Q06124 | 0 | dephosphorylation | down-regulates | 0.731 | Dca concomitantly and significantly increased association of tyrosine phosphatase shp2 with fak. Incubation of immunoprecipitated fak, in vitro, with glutathione-s-transferase-shp2 fusion protein resulted in tyrosine dephosphorylation of fak in a concentration-dependent manner. | SIGNOR-148926 |
Q99661 | Q96GD4 | 0 | phosphorylation | up-regulates | 0.731 | Here, we show that the binding of mcak to chromosome arms is also regulated by aurora b and that aurora b-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. Mcak association with chromosome arms is promoted by phosphorylation of t95 on mcak, whereas phosphorylation of s196 on mcak promotes dissociation from the arms. Although targeting of mcak to centromeres requires phosphorylation of s110 on mcak, dephosphorylation of t95 on mcak increases the binding of mcak to centromeres. | SIGNOR-155890 |
P15172 | P84022 | 0 | binding | down-regulates activity | 0.731 | We show that the TGF-beta intracellular effector Smad3, but not Smad2, mediates the inhibition of myogenic differentiation in MyoD-expressing C3H10T1/2 cells and C2C12 myoblasts by repressing the activity of the MyoD family of transcriptional factors. | SIGNOR-252071 |
P49815 | P49841 | 0 | phosphorylation | up-regulates activity | 0.731 | Gsk3 inhibits the mtor pathway by phosphorylating tsc2 in a manner dependent on ampk-priming phosphorylation. | SIGNOR-149380 |
P42702 | Q16619 | 0 | binding | up-regulates | 0.731 | We conclude that gp130/lif receptor and et(a) receptor activation are essential for cardiac fibroblast growth by ct-1 | SIGNOR-114758 |
P16220 | O75582 | 0 | phosphorylation | up-regulates | 0.731 | Msk1 is localized in the nucleus of unstimulated or stimulated cells, and phosphorylates creb at ser133_ .MSK1 Is activated in vitro by mapk2/erk2 or sapk2/p38. Endogenous msk1 is activated in 293 cells by either growth factor/phorbol ester stimulation, or by exposure to uv radiation, and oxidative and chemical stres msk was the kinase responsible for phosphorylation of the transcription factor creb in response to tcr stimulation. Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb. | SIGNOR-59458 |
Q9Y266 | P53350 | 0 | phosphorylation | up-regulates activity | 0.73 | Here, we characterize the interaction between plk1 and nudc, show that plk1 phosphorylates nudc at conserved s274 and s326 residues in vitro, and present evidence that nudc is also a substrate for plk1 in vivo. Downregulation of nudc by rna interference results in multiple mitotic defects, including multinucleation and cells arrested at the midbody stage, which are rescued by ectopic expression of wild-type nudc, but not by nudc with mutations in the plk1 phosphorylation sites. | SIGNOR-103403 |
P29966 | P17252 | 0 | phosphorylation | down-regulates activity | 0.73 | Here we report that MARCKS is a filamentous (F) actin crosslinking protein, with activity that is inhibited by PKC-mediated phosphorylation and by binding to calcium-calmodulin | SIGNOR-249650 |
Q9HBW1 | Q96CW9 | 0 | binding | up-regulates activity | 0.73 | The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. | SIGNOR-264048 |
P56211 | Q96GX5 | 0 | phosphorylation | up-regulates activity | 0.73 | We identified cyclic adenosine monophosphateregulated phosphoprotein 19 (Arpp19) and -Endosulfine as two substrates of Gwl that, when phosphorylated by this kinase, associate with and inhibit PP2A, thus promoting mitotic entry. | SIGNOR-243611 |
P06241 | P08575 | 0 | dephosphorylation | up-regulates activity | 0.73 | On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction. | SIGNOR-248352 |
P20645 | O60664 | 0 | relocalization | up-regulates activity | 0.73 | TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi. | SIGNOR-253093 |
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