Phosphorylation of frizzled-3.
Wnts are secreted proteins important to many biological processes. frizzled genes encode a family of Wnt receptors that signal to the intracellular compartment through the cytosolic protein Disheveled. Limited information is available concerning the regulation of Frizzleds at a biochemical level. We report here that Xenopus Frizzled-3 is phosphorylated in a Disheveled-dependent manner that appears to require the DEP domain of Disheveled. Phosphorylation of serine 576 causes a decrease in electrophoretic mobility and accounts for a significant fraction of receptor phosphorylation, although additional residues in the C-terminal tail are also phosphorylated. In addition, mutations that interfere with Frizzled-3 function also interfere with phosphorylation, but these inactive mutants can be phosphorylated when an active form of Frizzled-3 is co-expressed. Mutation of C-terminal serines including serine 576 significantly enhances Frizzled-3-mediated induction of neural crest markers, suggesting that C-terminal phosphorylation plays a role in down-regulating Frizzled signaling.
Yanfeng
Wang A
WA
Cell and Molecular Biology Graduate Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Tan
Change
C
Fagan
Robert J
RJ
Klein
Peter S
PS
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000072261:Dishevelled Proteins; D015536:Down-Regulation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D047468:Immunoprecipitation; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; C486340:FZD3 protein, Xenopus; D051157:Frizzled Receptors; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D029867:Xenopus Proteins