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).
Qin
Yuanbo
Y
State Key Laboratory of Molecular Biology and Center of Cell Signaling, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Li
Lin
L
Pan
Weijun
W
Wu
Dianqing
D
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D000072261:Dishevelled Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D047468:Immunoprecipitation; D015778:Minor Histocompatibility Antigens; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000494:pharmacology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D015778:Minor Histocompatibility Antigens; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C037178:phosphatidylinositol 4-phosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; C020077:1-phosphatidylinositol-4-phosphate 5-kinase