Regulation of Phosphatidylinositol Kinases and Metabolism by Wnt3a and Dvl
Regulation of Phosphatidylinositol Kinases and Metabolism by Wnt3a and Dvl
Wnt signaling plays important roles in various physiological and pathophysiological processes. The pathway that leads to beta-catenin stabilization is initiated by Wnt binding to its cell surface receptors, which induces the formation of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) via activation of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) type I. Here, we show that Wnt also stimulated the production of phosphatidylinositol 4-phosphate (PtdIns(4)P), which depended on Frizzled (Fz), Dishevelled (Dvl), and phosphatidylinositol 4-kinase (PI4K) type II alpha in HEK293T cells. Dvl directly interacted with and activated PI4KII alpha by increasing its V(max) for ATP and PtdIns. In addition, Dvl regulated PI4KII alpha and PIP5KI via different domains. Moreover, Dvl, PI4KII alpha, and PIP5KI appeared to form a ternary complex upon Wnt3a stimulation. This complex may allow efficient production of PtdIns(4,5)P(2) from PtdIns, which is far more abundant than PtdIns(4)P in cells. Therefore, this study provides new insights into the mechanism by which Wnt3a regulates the production of PtdIns(4,5)P(2).
- Chinese Academy of Sciences China (People's Republic of)
- MRC Laboratory of Molecular Biology United Kingdom
- Yale University United States
- Shanghai Institutes for Biological Sciences China (People's Republic of)
- Center for Excellence in Molecular Cell Science China (People's Republic of)
Dishevelled Proteins, Enzyme-Linked Immunosorbent Assay, Phosphoproteins, Cell Line, Protein Structure, Tertiary, Minor Histocompatibility Antigens, Wnt Proteins, Wnt3 Protein, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol Phosphates, Wnt3A Protein, Humans, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Protein Binding
Dishevelled Proteins, Enzyme-Linked Immunosorbent Assay, Phosphoproteins, Cell Line, Protein Structure, Tertiary, Minor Histocompatibility Antigens, Wnt Proteins, Wnt3 Protein, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol Phosphates, Wnt3A Protein, Humans, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Protein Binding
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