BioPAX pathway converted from "WNT mediated activation of DVL" in the Reactome database.WNT mediated activation of DVLThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.11CSNK2-mediated phosphorylation of DVLThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeDVLReactome DB_ID: 10109050DVL1DVL1F1RJE5Reactome DB_ID: 10109044cytosolGENE ONTOLOGYGO:0005829UniProt:F1RJE5DVL1Sus scrofaNCBI Taxonomy9823UniProtF1RJE51EQUAL695EQUALReactome Database ID Release 7510109044Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109044ReactomeR-SSC-2016871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201687.1Reactomehttp://www.reactome.orgDVL2DVL2A0A287AJQ6Reactome DB_ID: 10109046UniProt:A0A287AJQ6DVL2UniProtA0A287AJQ61EQUAL736EQUALReactome Database ID Release 7510109046Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109046ReactomeR-SSC-2016941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201694.1DVL3A0A287AAL7Reactome DB_ID: 10109048UniProt:A0A287AAL7UniProtA0A287AAL71EQUAL716EQUALReactome Database ID Release 7510109048Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109048ReactomeR-SSC-2016781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201678.1Reactome Database ID Release 7510109050Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109050ReactomeR-SSC-2017251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201725.1ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 113592ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 75113592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592ReactomeR-ALL-1135924Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.4COMPOUNDC00002additional informationMIMI:0361Converted from EntitySet in Reactomep-DVLReactome DB_ID: 10109059F1RJE5phospho-DVL1p-S-DVL1Reactome DB_ID: 10109053O-phospho-L-serineMODMOD:000461EQUAL695EQUALReactome Database ID Release 7510109053Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109053ReactomeR-SSC-2017001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201700.1p-DVL2phospho-DVL2A0A287AJQ6Reactome DB_ID: 10109055phosphorylated residueMODMOD:006961EQUAL736EQUALReactome Database ID Release 7510109055Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109055ReactomeR-SSC-2017061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201706.1A0A287AAL7phospho-p-DVL3Reactome DB_ID: 101090571EQUAL716EQUALReactome Database ID Release 7510109057Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109057ReactomeR-SSC-2016801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201680.1Reactome Database ID Release 7510109059Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109059ReactomeR-SSC-2016891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201689.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 29370ADP(3-) [ChEBI:456216]ADP(3-)ADP5'-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 7529370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370ReactomeR-ALL-293704Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.4COMPOUNDC00008ACTIVATIONCasein kinase IIReactome DB_ID: 10109081Converted from EntitySet in ReactomeCSNK2(A1:A1/A1:A2/A2:A2)CKII alpha catalytic subunitReactome DB_ID: 10109079CSNK2A1 dimerReactome DB_ID: 10109069F2Z5I5CSNK2A1CSNK2A1Reactome DB_ID: 10109067UniProt:F2Z5I5CSNK2A1UniProtF2Z5I51EQUAL391EQUALReactome Database ID Release 7510109067Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109067ReactomeR-SSC-2017131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201713.12Reactome Database ID Release 7510109069Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109069ReactomeR-SSC-50836211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5083621.1CSNK2A2 dimerReactome DB_ID: 10109075K9IVE3CSNK2A2Reactome DB_ID: 10109073UniProt:K9IVE3UniProtK9IVE31EQUAL350EQUALReactome Database ID Release 7510109073Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109073ReactomeR-SSC-2017211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201721.12Reactome Database ID Release 7510109075Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109075ReactomeR-SSC-50836201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5083620.1CSNK2A1:CSNK2A2Reactome DB_ID: 1010907711Reactome Database ID Release 7510109077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109077ReactomeR-SSC-50836231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5083623.1Reactome Database ID Release 7510109079Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109079ReactomeR-SSC-50836241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5083624.12CSNK2BCSNK2BP67872Reactome DB_ID: 10109063UniProt:P67872CSNK2BUniProtP678722EQUAL215EQUALReactome Database ID Release 7510109063Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109063ReactomeR-SSC-2016931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201693.12Reactome Database ID Release 7510109081Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109081ReactomeR-SSC-2017111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201711.1GENE ONTOLOGYGO:0004674gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510109082Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109082Reactome Database ID Release 7510109084Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10109084ReactomeR-SSC-2017171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201717.1DVL proteins from Drosophila, Xenopus, mouse and human cells have been shown to be phosphorylated, however the role of phosphorylation remains incompletely understood (Willert et al, 1997; Semenov and Synder, 1997; Yanagawa et al, 1995; Rothbächer et al, 2000). CSNK2 was identified as a DVL-associated kinase in Drosophila cells, and was shown to mediate the phosphorylation of serine and threonine residues in vitro (Willert et al, 1997). CSNK2-mediated phosphorylation of DVL may be constitutive, as DVL exists as a phosphoprotein even in the absence of WNT signaling (Bernatik et al, 2011). The association between DVL and CSNK2 may be enhanced upon WNT signaling, leading to increased levels of DVL phosphorylation (Willert et al, 2007).7744250Pubmed1995The dishevelled protein is modified by wingless signaling in DrosophilaYanagawa, Shin-ichivan Leeuwen, FrankWodarz, AndreasKlingensmith, JohnNusse, RoelGenes Dev. 9:1087-979214626Pubmed1997Casein kinase 2 associates with and phosphorylates dishevelledWillert, KarlBrink, MarcelWodarz, AndreasVarmus, HNusse, RoelEMBO J. 16:3089-9610698942Pubmed2000Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesisRothbächer, UteLaurent, Micheline NDeardorff, Matthew AKlein, Peter SCho, Ken WFraser, Scott EEMBO J. 19:1010-2221285348Pubmed2011Sequential activation and inactivation of Dishevelled in the Wnt/beta-catenin pathway by casein kinasesBernatik, OndrejGanji, Ranjani SriDijksterhuis, Jacomijn PKonik, PeterCervenka, IgorPolonio, TilmanKrejci, PSchulte, GunnarBryja, VJ. Biol. Chem. 286:10396-4109192851Pubmed1997Human dishevelled genes constitute a DHR-containing multigene familySemënov, Mikhail VSnyder, MichaelGenomics 42:302-10inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHT2.7.11WNT signaling stimulates CSNK1-dependent phosphorylation of DVLThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in Reactomepp-DVLReactome DB_ID: 10108986F1RJE5phospho-DVL1pp-DVL1Reactome DB_ID: 101089741EQUAL695EQUALReactome Database ID Release 7510108974Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10108974ReactomeR-SSC-37723961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772396.1pp-DVL2phospho-DVL2A0A287AJQ6Reactome DB_ID: 101089791EQUAL736EQUALReactome Database ID Release 7510108979Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10108979ReactomeR-SSC-37723981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772398.1A0A287AAL7phospho-pp-DVL3Reactome DB_ID: 101089841EQUAL716EQUALReactome Database ID Release 7510108984Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10108984ReactomeR-SSC-37724001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772400.1Reactome Database ID Release 7510108986Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10108986ReactomeR-SSC-37724071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772407.1ACTIVATIONCSNK1EI3LP46Reactome DB_ID: 10114536UniProt:I3LP46UniProtI3LP461EQUAL416EQUALReactome Database ID Release 7510114536Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10114536ReactomeR-SSC-2058771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-205877.1Reactome Database ID Release 7510149421Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149421Reactome Database ID Release 7510149423Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149423ReactomeR-SSC-37724351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772435.1CSNK1E and DVL physically interact in vivo and CSNK1E phosphorylates DVL in response to WNT signaling (Peters et al, 1999; Sakanaka et al, 1999; Kishida et al, 2001; Gao et al, 2002; Hino et al, 2003; Klimowski et al, 2006; Bernatik et al, 2011). Phosphorylation by CSNK1E in the PDZ domain of DVL appears to be required for the recruitment of AXIN and the subsequent phosphorylation of LRP6 (Bernatik et al, 2011).12556519Pubmed2003Casein kinase I epsilon enhances the binding of Dvl-1 to Frat-1 and is essential for Wnt-3a-induced accumulation of beta-cateninHino, Shin-ichiroMichiue, TatsuoAsashima, MakotoKikuchi, AkiraJ. Biol. Chem. 278:14066-7311425858Pubmed2001Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase IepsilonKishida, MichikoHino, Shin-ichiroMichiue, TatsuoYamamoto, HidekiKishida, ShoseiFukui, AkimasaAsashima, MakotoKikuchi, AkiraJ. Biol. Chem. 276:33147-5516965538Pubmed2006Site-specific casein kinase 1epsilon-dependent phosphorylation of Dishevelled modulates beta-catenin signalingKlimowski, Laura KGarcia, Benjamin AShabanowitz, JeffreyHunt, Donald FVirshup, David MFEBS J. 273:4594-60211818547Pubmed2002Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complexGao, ZHSeeling, JMHill, VYochum, AVirshup, DMProc Natl Acad Sci U S A 99:1182-710535959Pubmed1999Casein kinase iepsilon in the wnt pathway: regulation of beta-catenin functionSakanaka, CLeong, PXu, LHarrison, SDWilliams, LTProc Natl Acad Sci U S A 96:12548-5210517632Pubmed1999Casein kinase I transduces Wnt signalsPeters, John MMcKay, Renée MMcKay, James PGraff, Jonathan MNature 401:345-50LEFT-TO-RIGHTPhosphorylated DVL recruits PIP5K1B to the plasma membraneThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>I3LG49PIP5K1BPIP5K1BReactome DB_ID: 10136600UniProt:I3LG49PIP5K1BUniProtI3LG491EQUAL540EQUALReactome Database ID Release 7510136600Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10136600ReactomeR-SSC-18062161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-1806216.1ppDVL:PIP5K1BReactome DB_ID: 1014941811Reactome Database ID Release 7510149418Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149418ReactomeR-SSC-37724211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772421.1Reactome Database ID Release 7510149420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149420ReactomeR-SSC-37724341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772434.1DVL1 and 3 have been shown to co-immunoprecipitate with PIP5KB in HEK293 cells. This interaction is mediated by the N-terminal half of the kinase and the PDZ and DIX domain of DVL and recruits PIPK5B to the receptor complex. The interaction of DVL and PIP5KB is required for the WNT3A-dependent phosphorylation of LRP6 at serine 1490 and threonine 1479, as well as and the subsequent formation of the signalosome and recruitment of AXIN (Pan et al, 2008).18772438Pubmed2008Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylationPan, WeijunChoi, Sun-CheolWang, HeQin, YuanboVolpicelli-Daley, LauraSwan, LauraLucast, LouiseKhoo, CynthiaZhang, XiaowuLi, LAbrams, Charles SSokol, Sergei YWu, DianqingScience 321:1350-3LEFT-TO-RIGHT2.7.1.68DVL-associated PIP5K1B phosphorylates PI4P to PI(4,5)P2This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PI4PPhosphatidylinositol 4-phosphate1-phosphatidyl-1D-myo-inositol 4-phosphate1-phosphatidyl-1D-myo-inositol 4-phosphatesReactome DB_ID: 392417plasma membraneGENE ONTOLOGYGO:00058861-phosphatidyl-1D-myo-inositol 4-phosphate [ChEBI:17526]1-phosphatidyl-1D-myo-inositol 4-phosphateChEBICHEBI:17526Reactome Database ID Release 75392417Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=392417ReactomeR-ALL-3924173Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-392417.3COMPOUNDC01277PubChem Substance4496PIP2PI(4,5)P21-phosphatidyl-1D-myo-inositol 4,5-bisphosphatePhosphatidylinositol-4,5-bisphosphate1-phosphatidyl-1D-myo-inositol 4,5- bisphosphateReactome DB_ID: 1798561-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [ChEBI:18348]1-phosphatidyl-1D-myo-inositol 4,5-bisphosphatePIP2ChEBICHEBI:18348Reactome Database ID Release 75179856Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=179856ReactomeR-ALL-1798563Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-179856.3COMPOUNDC04637ACTIVATIONGENE ONTOLOGYGO:0016308Reactome Database ID Release 7510149424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149424Reactome Database ID Release 7510149426Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10149426ReactomeR-SSC-37724361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3772436.1Stimulation of the WNT pathway controls the activity of PIP5KB in a FZD- and DVL-dependent manner (Pan et al, 2008; Bilic et al, 2007; Cong et al, 2004; Qin et al, 2009). Activation of PIP5KB results in the formation of PI(4,5)P2 at the plasma membrane, which is required through an unclear mechanism for the phosphorylation of LRP6 at serine 1490, LRP6 aggregation into 'signalosomes' and LRP6 phosphorylation at threonine 1479. These events are required for the recruitment of AXIN to the plasma membrane (Pan et al, 2008; Qin et al, 2009).15459103Pubmed2004Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRPCong, FSchweizer, LVarmus, HDevelopment 131:5103-1519561074Pubmed2009Regulation of phosphatidylinositol kinases and metabolism by Wnt3a and DvlQin, YuanboLi, LPan, WeijunWu, DianqingJ. Biol. Chem. 284:22544-817569865Pubmed2007Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylationBilic, JHuang, YLDavidson, GaryZimmermann, TCruciat, CMBienz, MNiehrs, CScience 316:1619-22Reactome Database ID Release 7510185881Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10185881ReactomeR-SSC-2016881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-201688.1The three human Dishevelled (DVL) proteins play a central and overlapping role in the transduction of the WNT signaling cascade (Lee et al, 2008; reviewed in Gao and Chen 2010). DVL activity is regulated by phosphorylation, although the details are not completely worked out. DVL likely exists as a phosphoprotein even in the absence of WNT stimulation, and is further phosphorylated upon ligand binding. Casein kinase 1epsilon (CSNK1E), casein kinase 2 (CSNK2) and PAR1 have all been reported to phosphorylate DVL (Willert et al, 1997; Sun et al, 2001; Cong et al, 2004; Ossipova et al, 2005). Upon pathway activation, phosphorylated DVL translocates to the plasma membrane through an interaction between the DVL PDZ domain and the FZD KTxxxW motif (Wong et al, 2003; Umbhauer et al, 2000; Kikuchi et al, 2011). At the plasma membrane, DVL is believed to oligomerize through its DIX domain, providing a platform for AXIN recruitment; recruitment of AXIN is also facilitated by interaction with LRP (Schwarz-Romond et al, 2007; Mao et al, 2001). DVL interacts with phosphatidylinositol-4-kinase type II (PI4KII) and phophatidylinositol-4-phosphate 5-kinase type I (PIP5KI) to promote formation of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in the membrane, which is required for the clustering and phosphorylation of LRP6 and the recruitment of AXIN (Pan et al, 2008; Qin et al, 2009).14636582Pubmed2003Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of FrizzledWong, HCBourdelas, AKrauss, ALee, HJShao, YWu, DMlodzik, MShi, DLZheng, JMol Cell 12:1251-6017529994Pubmed2007The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerizationSchwarz-Romond, ThomasFiedler, MarcShibata, NaokiButler, P Jonathan GKikuchi, AkiraHiguchi, YoshikiBienz, MNat. Struct. Mol. Biol. 14:484-9211433294Pubmed2001PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signallingSun, Tian QiangLu, BingweiFeng, Jia JiaReinhard, ChristophJan, YNFantl, Wendy JWilliams, LTNat. Cell Biol. 3:628-3622017973Pubmed2011New insights into the mechanism of Wnt signaling pathway activationKikuchi, AkiraYamamoto, HidekiSato, AkiraMatsumoto, ShinjiInt Rev Cell Mol Biol 291:21-7120006983Pubmed2010Dishevelled: The hub of Wnt signalingGao, ChanChen, Ye-GuangCell. Signal. 22:717-2711336703Pubmed2001Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathwayMao, JWang, JLiu, BPan, WFarr GH, 3rdFlynn, CYuan, HTakada, SKimelman, DLi, LWu, DMol Cell 7:801-918093802Pubmed2008Differential mediation of the Wnt canonical pathway by mammalian Dishevelleds-1, -2, and -3Lee, Yi-NanGao, YuanWang, Hsien-YuCell. Signal. 20:443-5215935773Pubmed2005Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate developmentOssipova, OlgaDhawan, SangeetaSokol, SergeiGreen, Jeremy B ADev. Cell 8:829-4110990458Pubmed2000The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signallingUmbhauer, MurielDjiane, AlexandreGoisset, CélinePenzo-Mendèz, AlfredoRiou, Jean-FrançoisBoucaut, Jean-ClaudeShi, De-LiEMBO J. 19:4944-54