Wnt signaling and heterotrimeric G-proteins: strange bedfellows or a classic romance?
Biochem Biophys Res Commun
; 287(3): 589-93, 2001 Sep 28.
Article
en En
| MEDLINE
| ID: mdl-11563835
Wnts are secreted ligands with diverse roles in animal development. Wnts bind to cell surface membrane proteins termed Frizzleds. Molecular cloning of members of the Frizzled family revealed hydropathy plots with seven putative, transmembrane-spanning regions, conserved in Frizzleds characterized in mice, humans, flies, and worms. Understanding how Frizzled translates binding of their cognate Wnts into intracellular signals controlling aspects of development has been an elusive goal. Earlier observations gathered from a variety of model systems provided compelling, but indirect, support that the Frizzled receptors may be members of the superfamily of G-protein-coupled receptors that possess seven transmembrane-spanning domains. Search for a linkage between Frizzled and possible downstream heterotrimeric G-proteins has been advanced by the use of bacterial toxins, antisense DNA, and novel chimeric receptor constructs. New data establish that Frizzleds are indeed bona fide G-protein-coupled receptors. Frizzled-1 couples via G-proteins Go and Gq to the canonical beta-catenin-Lef-Tcf pathway. Frizzled-2 couples via Gq and Gt to downstream effectors including calcium mobilization. Frizzleds and G-proteins might once have been considered strange bedfellows, not likely partners in signaling. The new data, consistent with the properties known for virtually all members of the G-protein-coupled receptors, reveal a more classic romance of signaling elements controlling aspects of early development.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Transactivadores
/
Proteínas Proto-Oncogénicas
/
Proteínas de Unión al GTP
/
Proteínas de Pez Cebra
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos