The Identification and Cloning of the Wnt-1 Receptor
Abstract
In mice, ectopic activation of certain wnt genes, such as wnt-1, causes the formation of mammary tumors, providing a potential model for human breast cancer. However, Wnt receptors, essential components mediating the Wnt oncogenic function, had not been identified. It was shown recently that in Drosophila, DFz2, a member of the Frizzled (Fz) family of seven transmembrane receptors, functions as a receptor for Wingless protein, the ortholog of Wnt-1. This implies that the family of Fz proteins are likely to function as receptors for Wnt molecules. However, the scarcity of soluble Wnt proteins complicates the study of ligand-receptor relationships and their specificity. We have developed an approach in Xenopus to pursue the study. In Xenopus, Wnt molecules of Wingless/Wnt-1 subclass induce axis duplication whereas Wnt-5A subclass molecules do not. This dichotomy can be explained by activation of different signaling pathway(s), or lack of Wnt-5A receptor(s) during axis formation. We found that Wnt-5A induces axis duplication in the presence of hFz5, a member of the Frizzled protein family. Wnt-5A signaling via hFz5 is antagonized by glycogen synthase kinase-3 (GSK-3) and the N-terminal ectodomain of hFz5. These results identifies hFz5 as a receptor for Wnt-5A, and establishes axis induction in Xenopus as an approach to investigate relationships between Wnt and Fz proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADB225269
Entities
People
- Xi He
Organizations
- National Institutes of Health