Frizzled-9 Is Activated by Wnt-2 and Functions in Wnt/β-Catenin Signaling*

By T. Karasawa, H. Yokokura, J. Kitajewski, P. Lombroso. Journal of Biological Chemistry, 2002

97 citations recorded by the source corpus.

Frizzled has been known to function as a Wnt receptor. Although there have been a number of mammalian Frizzled members identified, their binding specificities with Wnt and functions in mammalian cells have been poorly understood. Here, we demonstrate that rat Frizzled-9 (Rfz9) functions in Wnt/β-catenin signaling in 293T cells. Rfz9 overexpression induces the hyperphosphorylation and relocalization of mouse Dishevelled-1 (Dvl-1) from the cytoplasm to the cell membrane and the accumulation of cytosolic β-catenin. Transfections of Rfz9 with each of several Wnt members show that only Wnt-2 activates Rfz9 in T cell factor (TCF)-dependent transcription. Deletion mutant analysis determines that there is a difference in Rfz9 C-terminal residues required for the modifications of Dvl-1 and those required for the inductions of β-catenin stabilization and TCF transactivation. Deletion of the Wnt-binding domain does not abolish Rfz9 activity completely, although it causes the inactivation of Wnt-2-dependent TCF transcription. Rfz9 also relocalizes Axin from the cytoplasm to the plasma membrane in the presence of Dvl-1, suggesting that one of the consequences of Dvl-1 relocalization by Rfz9 is to bring Axin to the cell membrane.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0ff7e27aa6d2fbb954379ee164a6b455aa6e331c

Citations in the corpus

• INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3 (2014, unknown): “However, all DVL-C mutants used in this study except for one failed to induce β-catenin accumulation (Karasawa et al., 2002).”