Wnt-frizzled signaling to G-protein-coupled effectors

被引:60
作者
Wang, HY [1 ]
Malbon, CC
机构
[1] SUNY Stony Brook, Hlth Sci Ctr, Dept Physiol & Biophys, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Hlth Sci Ctr, Dept Pharmacol, Stony Brook, NY 11794 USA
关键词
frizzled; Wnt; cell signaling; Ca++; cyclic GMP; PDE; development; G proteins; G-protein-coupled receptors;
D O I
10.1007/s00018-003-3165-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:69 / 75
页数:7
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