Lipid and Proteomic Analyses in Wnt Signaling

Dan Wu, Department of Pharmacology, Yale University

The Wnt family of glycoproteins is one of the major families of developmentally important signaling molecules. They are involved in the regulation of a variety of biological and pathophysiological processes that include synapse differentiation and function. The best characterized Wnt signaling pathway, the canonical Wnt signaling pathway, is initiated by the binding of canonical Wnts to their receptor complexes consisting of the LDL receptor-related protein (LRP) 5/6 and frizzled (Fz) proteins. Wnt subsequently induces the phosphorylation of LRP, leading to the stabilization of b-catenin and activation of gene transcription. Despite remarkable advances in our understanding of Wnt signaling mechanisms, significant gaps still remain. With the help of the Lipid Analysis Core, Wnt was found to stimulate PtdIns (4,5)P2 formation. In this study, we will continue the characterization of Wnt-induced PtdIns (4,5)P2 formation in a variety of different cell types, including the neuronal cells. In addition, we will elucidate the mechanisms by which Wnt regulates PtdIns (4,5)P22 formation. Moreover, we will use the Phosphoprotein Profiling Core to produce phosphoprotein profiles in response to Wnt treatment.