Regulation of phosphatidylinositol 4,5-bisphosphate levels and its roles in cytoskeletal re-organization and malignant transformation.
It is well known that phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) plays important roles not only as a precursor lipid for generating second messengers but also as a regulator of cytoskeletal re-organization. The last step of PtdIns(4,5)P2 synthesis is catalyzed by PtdIns monophosphate(PIP) kinase. So far, three type I PIP kinases(alpha, beta, and gamma), which phosphorylate PtdIns(4) to PtdIns(4,5)P2, and three type II PIP kinases(alpha, beta, gamma), which phosphorylate PtdIns(5)P to PtdIns(4,5)P2 have been found. On the other hand, several inositolpolyphosphate 5-phosphatases which convert PtdIns(4,5)P2 to PtdIns(4) are known. Among them, synaptojanin, which associates with tyrosine kinase receptors through an adaptor protein, Ash/Grb2, in response to growth factors, is capable of hydrolyzing PtdIns(4,5)P2 bound to actin regulatory proteins, resulting in actin filament re-organization downstream of tyrosine kinases.
Takenawa
T
T
Department of Biochemistry, University of Tokyo, Japan.
Itoh
T
T
Fukami
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K
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015290:Second Messenger Systems
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010770:Phosphotransferases; D020794:Receptor Protein-Tyrosine Kinases; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases