The Frizzled family of unconventional G-protein-coupled receptors.
The Frizzled (FZD) family of receptors is critically involved in embryogenesis, and there is substantial evidence that members of this family also regulate tissue homeostasis in many different organs in the adult. FZD receptors have seven transmembrane-spanning domains and are activated by the WNT family of lipoglycoproteins. Many aspects of FZD signal transduction and pharmacology are still unclear. In this review, we summarize recent advances and some of the key questions about the molecular pharmacology of FZDs, FZD-associated proteins and signal transduction. We also discuss what little is known about the pharmacological binding profiles and the degree of selectivity of WNTs and other extracellular ligands for FZDs. Finally, we focus on signaling events that occur as a direct consequence of FZD activation, signaling via the central phosphoprotein Dishevelled (DVL) and FZD coupling to heterotrimeric G proteins. Here, we outline the current state of knowledge on FZDs and FZD signal transduction and pinpoint aspects of debate and future directions.
Schulte
Gunnar
G
Section of Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden. gunnar.schulte@ki.se
Bryja
Vítezslav
V
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D000072261:Dishevelled Proteins; D004705:Endocytosis; D051157:Frizzled Receptors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D010750:Phosphoproteins / Q000502:physiology; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D051157:Frizzled Receptors; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins