Frizzled Smoothened Family of GPCRs

Signaling through the G protein-coupled frizzled/smoothened receptors plays a crucial role in a diverse array of developmental processes (Figure 5.2). The ten frizzled receptors (FzRs) known in humans may be activated by a plethora of Wingless (Wnt) ligands identified in mammals. These ligands belong to a family of protooncogenes. The "Wnt" denotes the relationship of this family to the Droso-phila segment polarity wingless gene and to its vertebrate ortholog, murine mammary tumor virus integration site 1, a mouse protooncogene. Smoothened (Smo) is the sole member of the family of smoothened receptors. Although signaling of Smo is initiated by members of the Hedgehog (Hh) family of ligands, the activity of Smo is unleashed upon binding of Hh to the 12-membrane spanning protein Patched (Ptc) that otherwise keeps Smo in its inactive state. The Hh signaling pathway is intimately linked to cell growth and differentiation, with physiological roles in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth.

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