GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Sato, A, Yamamoto, H, Sakane, H, Koyama, H and Kikuchi, A (2010) Wnt5a regulates distinct signalling pathways by binding to Frizzled2. EMBO J. 29:41-54


Wnt5a regulates multiple intracellular signalling cascades, but how Wnt5a determines the specificity of these pathways is not well understood. This study examined whether the internalization of Wnt receptors affects the ability of Wnt5a to regulate its signalling pathways. Wnt5a activated Rac in the beta-catenin-independent pathway, and Frizzled2 (Fz2) and Ror1 or Ror2 were required for this action. Fz2 was internalized through a clathrin-mediated route in response to Wnt5a, and inhibition of clathrin-dependent internalization suppressed the ability of Wnt5a to activate Rac. As another action of Wnt5a, it inhibited Wnt3a-dependent lipoprotein receptor-related protein 6 (LRP6) phosphorylation and beta-catenin accumulation. Wnt3a-dependent phosphorylation of LRP6 was enhanced in Wnt5a knockout embryonic fibroblasts. Fz2 was also required for the Wnt3a-dependent accumulation of beta-catenin, and Wnt5a competed with Wnt3a for binding to Fz2 in vitro and in intact cells, thereby inhibiting the beta-catenin pathway. This inhibitory action of Wnt5a was not affected by the impairment of clathrin-dependent internalization. These results suggest that Wnt5a regulates distinct pathways through receptor internalization-dependent and -independent mechanisms.


PubMed PMC2808370 Online version:10.1038/emboj.2009.322


Animals; Binding, Competitive; CHO Cells; Cell Line; Clathrin/metabolism; Cricetinae; Cricetulus; Frizzled Receptors/metabolism; HeLa Cells; Humans; L Cells (Cell Line); LDL-Receptor Related Proteins/metabolism; Low Density Lipoprotein Receptor-Related Protein-6; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphorylation; Protein Binding; Proto-Oncogene Proteins/antagonists & inhibitors; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/pharmacology; RNA, Small Interfering/genetics; Receptors, G-Protein-Coupled/metabolism; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Signal Transduction; Wnt Proteins/antagonists & inhibitors; Wnt Proteins/deficiency; Wnt Proteins/genetics; Wnt Proteins/metabolism; Wnt Proteins/pharmacology; Wnt3 Protein; Wnt3A Protein; beta Catenin/metabolism; rac GTP-Binding Proteins/metabolism