Wnt-frizzled signaling to G-protein-coupled effectors.
Wnt proteins signal via cell surface receptors termed Frizzleds. Frizzleds display many properties characteristic of members of the superfamily of G-protein-coupled receptors, including heptihelical hydropathy plots; an exofacial N-terminal region that is glycosylated; a cytoplasmic C-terminal region that includes canonical motifs for phosphorylation by protein kinase A, protein kinase C and casein kinase II; cytoplasmic domains that couple to heterotrimeric G proteins, as evidenced by a GTP-shift in receptor affinity; receptor-mediated responses sensitive to depletion of specific G protein subunits and receptor-mediated responses sensitive to bacterial toxins that target G proteins. Evidence from a variety of developmental systems demonstrates Wnt-Frizzled (Fz) signaling via pathways other than the Wnt/beta-catenin pathway linked to transcription controlled by Lef/Tcf. Prominent among these additional pathways is a Wnt-Fz pathway regulating intracellular [Ca(++)] and cyclic GMP levels. The essential role of heterotrimeric G proteins in Wnt-Fz signaling is highlighted.
Wang
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Department of Physiology and Biophysics, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8661, USA. wangh@pharm.sunysb.edu
Malbon
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D000818:Animals; D008322:Mammals; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014714:Vertebrates; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C