Yellow submarine of the Wnt/Frizzled signaling: submerging from the G protein harbor to the targets

Biochem Pharmacol. 2011 Nov 15;82(10):1311-9. doi: 10.1016/j.bcp.2011.06.005. Epub 2011 Jun 13.


The Wnt/Frizzled signaling pathway plays multiple functions in animal development and, when deregulated, in human disease. The G-protein coupled receptor (GPCR) Frizzled and its cognate heterotrimeric Gi/o proteins initiate the intracellular signaling cascades resulting in cell fate determination and polarization. In this review, we summarize the knowledge on the ligand recognition, biochemistry, modifications and interacting partners of the Frizzled proteins viewed as GPCRs. We also discuss the effectors of the heterotrimeric Go protein in Frizzled signaling. One group of these effectors is represented by small GTPases of the Rab family, which amplify the initial Wnt/Frizzled signal. Another effector is the negative regulator of Wnt signaling Axin, which becomes deactivated in response to Go action. The discovery of the GPCR properties of Frizzled receptors not only provides mechanistic understanding to their signaling pathways, but also paves new avenues for the drug discovery efforts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Humans
  • Signal Transduction / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*


  • Frizzled Receptors
  • Wnt Proteins
  • GTP-Binding Proteins