Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions

• Published in: Nature (London) 2002-11, Vol.420 (6911), p.89-93
• Main Authors: Anderson, Richard A, Ling, Kun, Doughman, Renee L, Firestone, Ari J, Bunce, Matthew W
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Binding Sites; Biological and medical sciences; Cell Line; Cell Membrane - enzymology; Cell Membrane - metabolism; Cell physiology; Cell structures and functions; Cytoskeleton, cytoplasm. Intracellular movements; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; Integrin beta Chains - metabolism; Isoenzymes - chemistry; Isoenzymes - genetics; Isoenzymes - metabolism; letter; Mice; Molecular and cellular biology; multidisciplinary; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphotransferases (Alcohol Group Acceptor) - chemistry; Phosphotransferases (Alcohol Group Acceptor) - genetics; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Protein Binding; Protein-Tyrosine Kinases - metabolism; Rats; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Science; Science (multidisciplinary); Signal transduction; Talin - chemistry; Talin - metabolism; Vinculin - metabolism
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature01082

The ability of cells to form cell contacts, adhere to the extracellular matrix, change morphology, and migrate is essential for development, wound healing, metastasis, cell survival and the immune response. These events depend on the binding of integrin to the extracellular matrix, and assembly of focal adhesions, which are complexes comprising scaffolding and signalling proteins organized by adhesion to the extracellular matrix. Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin. The binding of talin to β-integrin is strengthened by PtdIns(4,5)P2, suggesting that the basis of focal adhesion assembly is regulated by this lipid mediator. Here we show that the type I phosphatidylinositol phosphate kinase isoform-γ 661 (PIPKIγ661), an enzyme that makes PtdIns(4,5)P2, is targeted to focal adhesions by an association with talin. PIPKIγ661 is tyrosine phosphorylated by focal adhesion associated kinase signalling, increasing both the activity of phosphatidylinositol phosphate kinase and its association with talin. This defines a mechanism for spatial generation of PtdIns(4,5)P2 at focal adhesions.