title: Dishevelled activates Ca2+ flux, PKC, and CamKII in vertebrate embryos.
abstract: Wnt ligands and Frizzled (Fz) receptors have been shown to activate multiple intracellular signaling pathways. Activation of the Wnt-beta-catenin pathway has been described in greatest detail, but it has been reported that Wnts and Fzs also activate vertebrate planar cell polarity (PCP) and Wnt-Ca2+ pathways. Although the intracellular protein Dishevelled (Dsh) plays a dual role in both the Wnt-beta-catenin and the PCP pathways, its potential involvement in the Wnt-Ca2+ pathway has not been investigated. Here we show that a Dsh deletion construct, XDshDeltaDIX, which is sufficient for activation of the PCP pathway, is also sufficient for activation of three effectors of the Wnt-Ca2+ pathway: Ca2+ flux, PKC, and calcium/calmodulin-dependent protein kinase II (CamKII). Furthermore, we find that interfering with endogenous Dsh function reduces the activation of PKC by Xfz7 and interferes with normal heart development. These data suggest that the Wnt-Ca2+ pathway utilizes Dsh, thereby implicating Dsh as a component of all reported Fz signaling pathways.
authors.affiliation: Howard Hughes Medical Institute, Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Laird C
authors.initials: LC
authors.lastname: Sheldahl
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
authors.forename: Petra
authors.initials: P
authors.lastname: Pandur
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Miller
authors.forename: Michael
authors.initials: M
authors.lastname: Kühl
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017403:In Situ Hybridization; D037342:Pertussis Toxin / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D037342:Pertussis Toxin; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium