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>dshDVL1P51140Reactome DB_ID: 10506629cytosolGENE ONTOLOGYGO:0005829UniProt:P51140 dshdshCG18361FUNCTION Required to establish coherent arrays of polarized cells and segments in embryos. Plays a role in wingless (wg) signaling, possibly through the reception of the wg signal by target cells and subsequent redistribution of arm protein in response to that signal in embryos. This signal seems to be required to establish planar cell polarity and identity.SUBUNIT Interacts with nkd. This interaction may require zinc.TISSUE SPECIFICITY Found in egg chambers of the ovary and ubiquitously throughout embryogenesis and in disks. Expression is not seen in salivary glands, muscles or ventral ganglia but is observed in brain lobes.DEVELOPMENTAL STAGE Expressed at high levels at 0-1 hour and from 5-17 hours. Also expressed at high levels in early pupae.PTM Phosphorylated. Wg signaling generates the hyperphosphorylated active forms.SIMILARITY Belongs to the DSH family.Drosophila melanogasterNCBI Taxonomy7227UniProtP511401EQUAL695EQUALReactome Database ID Release 7510506629Database 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=10506629ReactomeR-DME-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-DME-201687.1Reactomehttp://www.reactome.orgATPAdenosine 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:0361P51140phospho-dshp-S-DVL1Reactome DB_ID: 10506636O-phospho-L-serineMODMOD:000461EQUAL695EQUALReactome Database ID Release 7510506636Database 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=10506636ReactomeR-DME-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-DME-201700.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 29370ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-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: 10506660CSNK2BCkIIbetaP08182Reactome DB_ID: 10506644UniProt:P08182 CkIIbetaCkIIbetaCask-II-bCG15224FUNCTION Participates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.SUBUNIT Tetramer of two alpha and two beta subunits.PTM Phosphorylated by alpha subunit.SIMILARITY Belongs to the casein kinase 2 subunit beta family.UniProtP081822EQUAL215EQUALReactome Database ID Release 7510506644Database 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=10506644ReactomeR-DME-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-DME-201693.12Converted from EntitySet in ReactomeCSNK2(A1:A1/A1:A2/A2:A2)CKII alpha catalytic subunitReactome DB_ID: 10506658CSNK2A1 dimerReactome DB_ID: 10506650P08181CkIIalphaCSNK2A1Reactome DB_ID: 10506648UniProt:P08181 CkIIalphaCkIIalphaCask-II-aCG17520FUNCTION Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha chain contains the catalytic site. May participate in Wnt signaling.SUBUNIT Tetramer of two alpha and two beta chains.DISRUPTION PHENOTYPE RNAi-mediated knockdown results in mislocalization of mbm in interphase cells with partial localization to the cytoplasm as well as nucleolar expression.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.UniProtP081811EQUAL391EQUALReactome Database ID Release 7510506648Database 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=10506648ReactomeR-DME-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-DME-201713.12Reactome Database ID Release 7510506650Database 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=10506650ReactomeR-DME-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-DME-5083621.1CSNK2A2 dimerReactome DB_ID: 10506654P08181CkIIalphaCSNK2A2Reactome DB_ID: 105066521EQUAL350EQUALReactome Database ID Release 7510506652Database 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=10506652ReactomeR-DME-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-DME-201721.12Reactome Database ID Release 7510506654Database 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=10506654ReactomeR-DME-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-DME-5083620.1CSNK2A1:CSNK2A2Reactome DB_ID: 1050665611Reactome Database ID Release 7510506656Database 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=10506656ReactomeR-DME-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-DME-5083623.1Reactome Database ID Release 7510506658Database 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=10506658ReactomeR-DME-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-DME-5083624.12Reactome Database ID Release 7510506660Database 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=10506660ReactomeR-DME-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-DME-201711.1GENE ONTOLOGYGO:0004674gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510506661Database 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=10506661Reactome Database ID Release 7510506663Database 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=10506663ReactomeR-DME-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-DME-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>P51140phospho-dshpp-DVL1Reactome DB_ID: 10506599phosphorylated residueMODMOD:006961EQUAL695EQUALReactome Database ID Release 7510506599Database 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=10506599ReactomeR-DME-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-DME-3772396.1ACTIVATIONdcoCSNK1EO76324Reactome DB_ID: 10537386UniProt:O76324 dcodcodbtCG2048FUNCTION Involved in circadian rhythms, viability and molecular oscillations of the clock genes period (per) and timeless (tim). Dbt reduces the stability and thus the accumulation of monomeric per proteins, probably through phosphorylation. No evident circadian oscillation is detected in head. Together with CkIalpha, regulates processing of ci by phosphorylating it which promotes its binding to slmb, the F-box recognition component of the SCF(slmb) E3 ubiquitin-protein ligase (PubMed:16326393).SUBUNIT Forms a complex with per (PubMed:9674431). Interacts with Dlish (PubMed:27692068).TISSUE SPECIFICITY Expressed in photoreceptor cells of the eyes as well as in the region situated between the optic lobe and the central brain.SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.UniProtO763241EQUAL416EQUALReactome Database ID Release 7510537386Database 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=10537386ReactomeR-DME-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-DME-205877.1Reactome Database ID Release 7510537387Database 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=10537387Reactome Database ID Release 7510537389Database 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=10537389ReactomeR-DME-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-DME-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>Converted from EntitySet in ReactomeHomologues of PIP5K1BReactome DB_ID: 10528241Q0E8Y1PIP5K59BPIP5K1BReactome DB_ID: 10528237UniProt:Q0E8Y1PIP5K59BUniProtQ0E8Y11EQUAL540EQUALReactome Database ID Release 7510528237Database 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=10528237ReactomeR-DME-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-DME-1806216.1sktlPIP5K1BQ9W2R3Reactome DB_ID: 10528239UniProt:Q9W2R3sktlUniProtQ9W2R31EQUAL540EQUALReactome Database ID Release 7510528239Database 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=10528239ReactomeR-DME-1806216-21Reactome 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-DME-1806216-2.1Reactome Database ID Release 7510528241Database 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=10528241ReactomeR-DME-1806216-31Reactome 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-DME-1806216-3.1ppDVL:PIP5K1BReactome DB_ID: 1053738011Reactome Database ID Release 7510537380Database 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=10537380ReactomeR-DME-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-DME-3772421.1Reactome Database ID Release 7510537382Database 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=10537382ReactomeR-DME-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-DME-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 7510537390Database 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=10537390Reactome Database ID Release 7510537392Database 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=10537392ReactomeR-DME-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-DME-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 7510568307Database 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=10568307ReactomeR-DME-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-DME-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. 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