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 |
|---|---|---|---|---|---|---|---|
Q15717 | Q05655 | 0 | phosphorylation | up-regulates | 0.637 | Tandem phosphorylation of serines 221 and 318 by protein kinase cdelta coordinates mrna binding and nucleocytoplasmic shuttling of hurstabilization of mrna by the ubiquitous rna binding protein human antigen r (hur), a member of the embryonic lethal abnormal vision (elav) protein family, requires canonical binding to au-rich element (are)-bearing target mrna and export of nuclear hur-mrna complexes to the cytoplasm. In human mesangial cells (hmc) both processes are induced by angiotensin ii (angii) via protein kinase cdelta (pkcdelta)-triggered serine phosphorylation of hur. | SIGNOR-163524 |
P60953 | O60890 | 0 | gtpase-activating protein | up-regulates activity | 0.637 | OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro | SIGNOR-268398 |
P45984 | O14733 | 0 | phosphorylation | up-regulates | 0.637 | Here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1). These results indicate that hgk, a novel activator of the jnk pathway, may function through tak1, and that the hgk --> tak1 --> mkk4, mkk7 --> jnk kinase cascade may mediate the TNF-alphalpha signaling pathway. | SIGNOR-83744 |
Q12888 | Q8N2W9 | 0 | sumoylation | up-regulates | 0.637 | Pias1 and pias4 are recruited to dna-damage sites and mediate 53bp1 recruitment and sumoylation | SIGNOR-162167 |
P17302 | P27361 | 0 | phosphorylation | down-regulates activity | 0.637 | These studies confirm that connexin-43 is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279, and/or Ser282 initiates the down-regulation of gap junctional communication. Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional intercellular communication. | SIGNOR-249466 |
O14543 | P42229 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.637 | We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling | SIGNOR-261548 |
O14964 | P00533 | 0 | phosphorylation | up-regulates activity | 0.637 | We have analysed hrs phosphorylation in response to epidermal growth factor (egf) stimulation and show that the evolutionary conserved tyrosines y329 and y334 provide the principal phosphorylation sitesover-expression of wild-type hrs or a double mutant, y329/334f, defective in egf-dependent phosphorylation, substantially retard egf receptor (egfr) degradation | SIGNOR-100246 |
Q05193 | P12931 | 0 | phosphorylation | up-regulates activity | 0.637 | Endocytosis of ligand-activated receptors requires dynamin-mediated GTP hydrolysis, which is regulated by dynamin self-assembly. Here, we demonstrate that phosphorylation of dynamin I by c-Src induces its self-assembly and increases its GTPase activity. Electron microscopic analyses reveal that tyrosine-phosphorylated dynamin I spontaneously self-assembles into large stacks of rings. Tyrosine 597 was identified as being phosphorylated both in vitro and in cultured cells following epidermal growth factor receptor stimulation. | SIGNOR-247129 |
Q8IW41 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.637 | In hela cells, prak was activated in response to cellular stress and proinflammatory cytokines. 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-58135 |
P19174 | Q08881 | 0 | phosphorylation | up-regulates | 0.637 | In t cells, the predominant tec kinase is itk, which functions downstream of the t-cell receptor to regulate phospholipase c-gamma. | SIGNOR-165803 |
O43521 | P45984 | 0 | phosphorylation | up-regulates activity | 0.637 | JNKs specifically phosphorylate BIMEL at Ser55, 65, and/or 73. several observations demonstrate that the phosphorylation of BIMEL is a physiologically important mechanism for enhancing its proapoptotic activity. | SIGNOR-250134 |
O95166 | O75385 | 0 | binding | up-regulates | 0.637 | N-terminal proline/serine rich (ps) domain of ulk1 (amino acid 287-416) is required for ulk1-gate-16 and ulk1-gabarap protein interactions | SIGNOR-85614 |
O14640 | P49674 | 0 | phosphorylation | up-regulates activity | 0.637 | Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development. | SIGNOR-217849 |
Q9ULW0 | P06493 | 0 | phosphorylation | down-regulates activity | 0.637 | In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. |Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle | SIGNOR-265096 |
P25106 | O14625 | 0 | binding | up-regulates activity | 0.637 | This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11) | SIGNOR-268415 |
Q9Y572 | Q9H171 | 0 | binding | up-regulates activity | 0.637 | ZBP1 initiates RIPK3-driven cell death by sensing IAV RNA and activating RIPK3. Here, we show that replicating IAV generates Z-RNAs, which activate ZBP1 in the nucleus of infected cells. ZBP1 then initiates RIPK3-mediated MLKL activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis. | SIGNOR-266430 |
Q9NPG1 | Q9H1J7 | 0 | binding | up-regulates | 0.636 | Human wnt5a, wnt5b and wnt11 are non-canonical wnt ligands transducing pcp signals through fzd3 or fzd6 receptors. | SIGNOR-141440 |
P61586 | Q8IW93 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.636 | 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-260543 |
Q9UJX2 | P06493 | 0 | phosphorylation | up-regulates | 0.636 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation | SIGNOR-119821 |
Q9UPT5 | P17081 | 0 | binding | up-regulates | 0.636 | Here we show that tc10 interacts with one of the components of the exocyst complex, exo70. | SIGNOR-100486 |
Q07889 | P27361 | 0 | phosphorylation | down-regulates | 0.636 | For example, inactivation of sos through phosphorylation by the downstream mapk | SIGNOR-26338 |
Q8NER5 | Q96S42 | 0 | binding | up-regulates activity | 0.636 | Human activin receptor-like kinase 7 (ALK7), a type I receptor for Nodal. activation of the Nodal-ALK7 signaling pathway leads to induction of apoptosis and inhibition of cell proliferation. | SIGNOR-251936 |
Q9HB75 | Q13315 | 0 | phosphorylation | up-regulates activity | 0.636 | ATM phosphorylates PIDD on Thr788 within the DD. This phosphorylation is necessary and sufficient for RAIDD binding and caspase-2 activation. Conversely, nonphosphorylatable PIDD fails to bind RAIDD or activate caspase-2, and engages prosurvival RIP1 instead. Thus, ATM phosphorylation of the PIDD DD enables a binary switch through which cells elect to survive or die upon DNA injury. | SIGNOR-262640 |
P21359 | Q7Z699 | 0 | binding | up-regulates quantity | 0.636 | Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. | SIGNOR-273660 |
P15498 | P06241 | 0 | phosphorylation | up-regulates | 0.636 | Study of t cells from a fyn-deficient tcr transgenic mouse also showed that fyn was required for tyrosine phosphorylation and activation of vav induced by both antagonist and agonist peptides. | SIGNOR-82287 |
P19174 | P12931 | 0 | phosphorylation | up-regulates activity | 0.636 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-247316 |
Q04721 | O00548 | 0 | binding | up-regulates | 0.636 | In this study, we demonstrate that dll1 can activate notch signaling mostly through notch2 receptor and can contribute to drug resistance to bortezomib, both in murine and human mm cells. | SIGNOR-199320 |
O43318 | Q9NQC7 | 0 | deubiquitination | up-regulates activity | 0.636 | Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. | SIGNOR-266437 |
Q9NRM7 | Q13043 | 0 | phosphorylation | up-regulates | 0.636 | Activation of mst1/2 leads to phosphorylation and activation of their direct substrates, lats1/2. | SIGNOR-175821 |
P10828 | P28702 | 0 | binding | up-regulates | 0.636 | Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr | SIGNOR-81455 |
P61586 | O60890 | 0 | gtpase-activating protein | up-regulates activity | 0.636 | OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro | SIGNOR-268397 |
P01112 | Q13671 | 0 | binding | up-regulates | 0.636 | We demonstrate that the ras effector protein rin1 binds to activated ras with an affinity (k(d), 22 nm) similar to that observed for raf1. | SIGNOR-113967 |
Q9ULB1 | Q99767 | 0 | binding | up-regulates activity | 0.636 | Mint1 and Mint2 Interact with the Cytoplasmic Domain of Neurexin I. The interaction of Mint1 with neurexins is mediated by its PDZ domains and allows the formation of mixed CASK-Mint complexes. Both CASK and Mint1 can bind directly to neurexins and to each other. Therefore, the assembly of various multimeric complexes could proceed as CASK could be indirectly recruited to neurexin-bound Mint1 and vice versa. | SIGNOR-264039 |
P37840 | P34947 | 0 | phosphorylation | down-regulates activity | 0.636 | Grk5 phosphorylated ser-129 of alpha-synuclein at the plasma membrane and induced translocation of phosphorylated alpha-synuclein to the perikaryal area. Grk5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of alpha-synuclein. | SIGNOR-149372 |
P19525 | Q13217 | 0 | binding | down-regulates activity | 0.635 | The protein p58IPK {also known asDnaJ3C [DnaJ heat-shock protein (hsp) 40 homologue, subfamily C, member 3]} is known to inhibit the eIF2 kinases PKR (dsRNA-dependent protein kinase/eIF2 kinase 2) and PERK | SIGNOR-246207 |
P15056 | P17612 | 0 | phosphorylation | down-regulates activity | 0.635 | Direct phosphorylation of B-Raf by PKA exerts a negative effect on its kinase activity, essentially via phosphorylation of Ser429 | SIGNOR-250339 |
Q53ET0 | Q9Y2K2 | 0 | phosphorylation | down-regulates activity | 0.635 | We found that QSK and SIK phosphorylated TORC2 at Ser171 as well as at least two additional residues, namely Ser70 and Ser348|QIK also phosphorylates the CREB co-activator TORC2, in unstimulated cells, to sequester it in the cell cytoplasm, thereby inhibiting CREB-dependent gene-expression | SIGNOR-249170 |
P49407 | Q99835 | 0 | binding | up-regulates | 0.635 | Grk2-mediated phosphorylation of vertebrate smo allows smo to bind to beta-arrestins 1 or 2 | SIGNOR-132678 |
Q99836 | P58753 | 0 | binding | up-regulates activity | 0.635 | Here we describe a protein, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TlR-domain-containing protein in the human genome. Mal activates NF-_B, Jun amino-terminal kinase and extracellular signal-regulated kinase-1 and -2. | SIGNOR-252063 |
P98155 | P02649 | 0 | binding | up-regulates | 0.635 | Several ligands for the vldl receptor have been identified in addition to tfpi. These include apolipoprotein e (apoe) | SIGNOR-106221 |
Q14114 | P06241 | 0 | phosphorylation | up-regulates quantity | 0.635 | Fyn phosphorylates ApoER2.|Together these data demonstrate that Fyn activity is necessary for its effects increasing ApoER2 levels. | SIGNOR-278197 |
P00533 | P17706 | 0 | dephosphorylation | down-regulates | 0.635 | Here, we report that the 45-kda variant of the protein tyrosine phosphatase tcptp (tc45) can recognize delta egfr as a cellular substrate | SIGNOR-132316 |
Q92793 | Q16566 | 0 | phosphorylation | up-regulates activity | 0.635 | Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301. | SIGNOR-250710 |
P35222 | P55291 | 0 | binding | up-regulates activity | 0.635 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265854 |
Q04721 | Q9Y219 | 0 | binding | up-regulates | 0.635 | Binding of delta1, jagged1, and jagged2 to notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of notch2 | SIGNOR-81367 |
O15085 | Q14344 | 0 | binding | up-regulates activity | 0.635 | This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein alpha subunits of the Galpha(12) family can bind and regulate the activity of RhoGEFs. Hence, these newly discovered RGL domain-containing RhoGEFs provide a direct link from Galpha(12) and Galpha(13) to Rho | SIGNOR-256517 |
P52272 | Q99459 | 0 | binding | up-regulates activity | 0.635 | hnRNP-M interacts directly with CDC5L and PLRG1 in vivo. we investigated whether the function of hnRNP-M in alternative splicing was affected by the central region mapped as essential for binding to the CDC5L/PLRG1 proteins. We conclude that loss of the CDC5L/PLRG1 interaction domain in hnRNP-M correlates with a loss of ability to modulate alternative splice site selection in this assay. | SIGNOR-239410 |
Q13614 | O95248 | 0 | binding | up-regulates activity | 0.635 | We also demonstrate that MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. Through this interaction, MTMR5 increases the enzymatic activity of MTMR2 and dictates its subcellular localization. | SIGNOR-269803 |
Q96T51 | P51813 | 0 | phosphorylation | up-regulates activity | 0.634 | Etk interacts with RUFY1 through its SH3 and SH2 domains. RUFY1 is tyrosine-phosphorylated and appears to be a substrate of Etk. Phosphorylation of the two tyrosine residues, Tyr-281 and Tyr-292, located in the linker region of the two coiled-coil domains by Etk seems to be critical for RUFY1 targeting to the endosomes. | SIGNOR-262679 |
Q15831 | O43524 | 0 | transcriptional regulation | down-regulates quantity | 0.634 | SGK-1 Negatively Regulates LKB1 Expression via FOXO3 Transcription Factor | SIGNOR-255758 |
P15923 | P41134 | 0 | binding | down-regulates activity | 0.634 | 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-241107 |
Q8WZ75 | O94813 | 0 | binding | up-regulates | 0.634 | We show that robo4 binds slit and inhibits cellular migration in a heterologous expression system, analogous to the role of known robo receptors in the nervous system. | SIGNOR-86380 |
Q15058 | O43663 | 0 | binding | up-regulates activity | 0.634 | KIF14 interacts with PRC1 and citron kinase. We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. I | SIGNOR-266423 |
Q06413 | Q9UKV0 | 0 | binding | down-regulates | 0.633 | Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner | SIGNOR-235642 |
P21579 | O60641 | 0 | binding | up-regulates quantity | 0.633 | the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively .Stonin-2 and AP-2 are also Required for Efficient Synaptotagmin-1 Retrieval. the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. | SIGNOR-264114 |
Q13480 | P27361 | 0 | phosphorylation | up-regulates activity | 0.633 | Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal | SIGNOR-249464 |
P61586 | P52306 | 0 | binding | up-regulates | 0.633 | Smggds is a guanine nucleotide exchange factor that specifically activates rhoa and rhoc | SIGNOR-171347 |
O00329 | P01116 | 0 | binding | up-regulates | 0.633 | Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85./it was also described that ras interacts with pi3k in a direct manner./lysine residue 227 is essential for the interaction of ras with pi3k | SIGNOR-175210 |
Q08209 | P53805 | 0 | binding | down-regulates activity | 0.633 | MCIP proteins can bind to and inhibit calcineurin, a calcium/calmodulin-regulated serine/threonine protein phosphatase that is activated during cardiac hypertrophy and failure | SIGNOR-252025 |
O75197 | Q9H1J5 | 0 | binding | up-regulates | 0.633 | 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-131987 |
P04150 | P0DMV8 | 0 | binding | down-regulates | 0.633 | Interestingly, FKBP51 forms complexes in mitochondria with the glucocorticoid receptor and the Hsp90/Hsp70-based chaperone heterocomplex | SIGNOR-251668 |
O75030 | P16220 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.633 | Therefore, the molecular steps linking cAMPto melanogenesis up-regulation appear currently better elucidated. cAMP activates PKA, and PKA phosphorylates and activates CREB which, when activated, binds to the CRE domain present in the microphthalmia promoter,thereby up-regulating its transcription. | SIGNOR-249619 |
P18848 | P51812 | 0 | phosphorylation | up-regulates | 0.633 | Here, we show that rsk2 is required for osteoblast differentiation and function. We identify the transcription factor atf4 as a critical substrate of rsk2 that is required for the timely onset of osteoblast differentiation, for terminal differentiation of osteoblasts, and for osteoblast-specific gene expression | SIGNOR-124436 |
P04049 | P28482 | 0 | phosphorylation | down-regulates activity | 0.632 | Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 | SIGNOR-249441 |
Q9HBY0 | Q86UR1 | 0 | binding | up-regulates activity | 0.632 | Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation | SIGNOR-264711 |
Q15691 | O75122 | 0 | binding | up-regulates activity | 0.632 | GSK-3beta directly phosphorylates CLASP2 at Ser533 and Ser537 within the region responsible for the IQGAP1 binding. Phosphorylation of CLASP2 results in the dissociation of CLASP2 from IQGAP1, EB1 and microtubules.| CLASPs were originally identified as CLIP-170-interacting proteins and later found to be required for microtubule stabilisation at the cortical regions of epithelial cells | SIGNOR-264829 |
Q9NPG1 | P56703 | 0 | binding | up-regulates | 0.632 | 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-131820 |
P53671 | Q13464 | 0 | phosphorylation | up-regulates | 0.632 | Specific activation of lim kinase 2 via phosphorylation of threonine 505 by rock, a rho-dependent protein kinase | SIGNOR-82755 |
P45983 | Q16828 | 0 | dephosphorylation | down-regulates activity | 0.632 | Our data demonstrate MKP-3 has differential substrate preference in astrocytes compared to other cells types, since it preferentially dephosphorylated p-JNK over p-ERK.|The main findings of our studies are (1) MKP-3 preferentially reduces p-JNK over p-ERK and p-p38 in primary astrocytes; (2) This MAPK modulation pattern in primary astrocytes significantly reduced NO and completely abolished IL-6 and TNF accumulation; and (3) These effects are specifically induced by MKP-3 since block-age of MKP-3 mRNA expression reversed its action on MAPKs and pro-inflammatory mediators in BV-2 microglia cells. | SIGNOR-277150 |
P36894 | O95393 | 0 | binding | up-regulates | 0.632 | We showed that three orphan ligands known to be important for joint and cartilage formation (gdf6) (10), interneuron, sensory neurons, and seminal vesicle formation (gdf7) (11_13), and heart development (bmp10) (14) used the type i receptors alk3 or alk6 and the type ii receptors bmprii or actriia to activate the smad1/5/8 proteins. | SIGNOR-139052 |
O75581 | P49840 | 0 | phosphorylation | up-regulates activity | 0.632 | Central to WNT signalosome formation is phosphorylation of LRP6 at multiple sites, with GSK3β phosphorylating LRP6 at S1490 and CK1 family members phosphorylating LRP6 at T1479 and T1493 | SIGNOR-275398 |
P46937-3 | P12931 | 0 | phosphorylation | up-regulates activity | 0.632 | We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. | SIGNOR-274025 |
O15530 | P48736 | 0 | binding | up-regulates | 0.632 | Recent reports have also shown that the phosphoinositide-dependent protein kinase-1 (pdk-1), which binds with high affinity to the pi 3-kinase lipid product phosphatidylinositol-3,4,5-trisphosphate (ptdins-3,4,5-p), phosphorylates and potently activates two other pi 3-kinase targets, the protein kinases akt/pkb and p70s6k. | SIGNOR-60567 |
Q15334 | P41743 | 0 | phosphorylation | up-regulates activity | 0.632 | This finding indicates that both mLgl-2 and mLgl-1 are phosphorylated in vivo in an aPKC lambda activity-dependent manner. | SIGNOR-263179 |
P60484 | O00308 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.632 | We have shown that WWP2 interacts with and ubiquitylates PTEN, promoting its degradation. | SIGNOR-278650 |
Q2M1P5 | Q99835 | 0 | relocalization | up-regulates activity | 0.632 | Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli proteins. | SIGNOR-209605 |
P60484 | O15327 | 0 | dephosphorylation | down-regulates activity | 0.632 | In support, the increase in PTEN caused by INPP4B knockdown was associated with increased phosphorylation of the Ser380, Thr382, Thr383 and Ser385 cluster of the protein (XREF_FIG), which is known to increase PTEN half-life, in colon cancer cells.|Exogenous INPP4B could pull down and dephosphorylate endogenous PTEN, suggesting that effect of INPP4B on PTEN in colon cancer cells is not due to cell-type-specific characteristics of INPP4B per se.|INPP4B downregulates PTEN in colon cancer cells. | SIGNOR-277018 |
Q9UI32 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.631 | Glutaminase 2 (GLS2) can be directly transactivated by p53 and can therefore mediate p53-dependent regulation of cellular energy metabolism. G | SIGNOR-268041 |
Q9H1D0 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.631 | In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine phosphatase inhibitor|PTP1B interacts with the N-terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co-immunoprecipitation, bimolecular fluorescence complementation and the yeast 2-hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src. Single mutations of Y161 or Y162 shows that each of both tyrosines alone is sufficient for the DMHV-effect. We conclude that phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293 cells. | SIGNOR-248433 |
P45985 | Q99683 | 0 | phosphorylation | up-regulates activity | 0.631 | A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase) | SIGNOR-45373 |
P14316 | Q7Z5L9 | 0 | binding | up-regulates activity | 0.631 | We have identified two novel proteins that interact specifically with the C-terminal repression domain of Interferon Regulatory Factor-2 (IRF-2). These proteins, which we term IRF-2 binding proteins 1 and 2 (IRF-2BP1 and IRF-2BP2, the latter having two splicing isoforms, A and B), are nuclear proteins, and have the properties of IRF-2-dependent transcriptional co-repressors that can inhibit both enhancer-activated and basal transcription in a manner that is not dependent upon histone deacetylation. | SIGNOR-224073 |
Q00613 | P27361 | 0 | phosphorylation | down-regulates | 0.631 | Sequential phosphorylation of hsf1 by mitogen-activated protein kinase and glycogen synthase kinase 3 at ser-303 and ser-307 represses transcriptional activation by heat shock factor-1. | SIGNOR-44999 |
Q99558 | Q9Y4K3 | 0 | binding | up-regulates activity | 0.631 | RANK activates NF-κB by interacting with TRAF6 via a novel TRAF6 interaction motif and TRAF6 potentially activates NIK, leading to NF-κB activation. TRAF6 has been demonstrated to interact with NIK. | SIGNOR-253048 |
Q9GZQ4 | Q5H8A3 | 0 | binding | up-regulates | 0.631 | Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan g protein-coupled receptor fm-4/tgr-1, which was identified to date as the neuromedin u (nmu) receptor, and designate this peptide 'neuromedin s (nms)' because it is specifically expressed in the suprachiasmatic nuclei (scn) of the hypothalamus. | SIGNOR-133131 |
P40763 | P22607 | 0 | phosphorylation | up-regulates activity | 0.631 | Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3. | SIGNOR-251139 |
P10276 | Q15596 | 0 | binding | up-regulates | 0.631 | Transcriptional coactivator for steroid receptors and nuclear receptors.nteracts with casp8ap2 and ttll5/stamp. Interacts with esr1, rara and rxra. | SIGNOR-96827 |
Q13485 | Q15831 | 0 | phosphorylation | down-regulates activity | 0.631 | LKB1 inhibits the DNA binding and the transcriptional activity of Smad4.|We further demonstrate that LKB1 is capable of phosphorylating Smad4 on Thr 77 of its DNA-binding domain. | SIGNOR-278193 |
P41182 | Q9Y618 | 0 | binding | up-regulates activity | 0.631 | The POZ domains of BCL-6 and several other POZ proteins interact with corepressors N-CoR and SMRT. | SIGNOR-252240 |
O95405 | P36897 | 0 | binding | up-regulates activity | 0.631 | Sara functions to recruit smad2 to the tgfbeta receptor by controlling the subcellular localization of smad2 and by interacting with the tgfbeta receptor complex | SIGNOR-62868 |
O15085 | Q03113 | 0 | binding | up-regulates activity | 0.631 | This RGS-like (RGL) domain provides a structural motif by which heterotrimeric G protein alpha subunits of the Galpha(12) family can bind and regulate the activity of RhoGEFs. Hence, these newly discovered RGL domain-containing RhoGEFs provide a direct link from Galpha(12) and Galpha(13) to Rho | SIGNOR-256516 |
P15336 | Q02930 | 0 | binding | up-regulates activity | 0.631 | CRE-BPa specifically binds to CRE as a homodimer or heterodimer with c-Jun or CRE-BP1. In CAT cotransfection experiments using CV-1 cells, transient expression of each of four CRE-BPa proteins caused a 1.6- to 3.4-fold increase of CRE-dependent transcription | SIGNOR-219655 |
P26715 | P17693 | 0 | binding | up-regulates | 0.631 | Current models of nk cell function have supposed that the cd94/nkg2a heterodimer is interacting with an epitope common to classical hla class i | SIGNOR-56714 |
Q99743 | P20393 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.631 | In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. | SIGNOR-267981 |
P49023 | Q13882 | 0 | phosphorylation | up-regulates activity | 0.63 | It was also observed that the attenuation of BRK phosphorylation in turn inhibits BRK mediated activation of its direct targets, STAT3, SAM68, and Paxillin.|The EGF pathway also stimulates BRK 's phosphorylation of paxillin to promote migratory and invasive characteristics in breast cancer cells. | SIGNOR-280102 |
Q96T51 | P61106 | 0 | relocalization | up-regulates activity | 0.63 | Here, we have demonstrated that Rab14 interacts with RUFY1, previously identified as a Rab4 effector, and is required for RUFY1 recruitment onto endosomes and efficient recycling of Tfn. | SIGNOR-261279 |
Q9NPG1 | Q93097 | 0 | binding | up-regulates | 0.63 | 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-131777 |
P15056 | Q8IVT5 | 0 | binding | up-regulates activity | 0.63 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273878 |
P08047 | Q04206 | 0 | binding | up-regulates | 0.63 | Rela (p65) nf-kappab subunit interacts with the zinc finger dna-binding domain of sp1. | SIGNOR-75004 |
P63027 | O60641 | 0 | binding | up-regulates quantity | 0.63 | the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval. | SIGNOR-264112 |
P09429 | Q9Y6Y9 | 0 | binding | up-regulates activity | 0.63 | Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. | SIGNOR-252058 |
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