Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.

Ling, Kun; Doughman, Renee L; Firestone, Ari J; Bunce, Matthew W; Anderson, Richard A

Ling, Kun; Doughman, Renee L; Firestone, Ari J; Bunce, Matthew W; Anderson, Richard A.

Afiliación

Ling K; Department of Pharmacology, Program in Molecular and Cellular Pharmacology, University of Wisconsin-Madison, 1300 University Avenue, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.

Nature ; 420(6911): 89-93, 2002 Nov 07.

Article en En | MEDLINE | ID: mdl-12422220

RESUMEN

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)P(2)) regulates interactions between these proteins, including the interaction of vinculin with actin and talin. The binding of talin to beta-integrin is strengthened by PtdIns(4,5)P(2), 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-gamma 661 (PIPKI gamma 661), an enzyme that makes PtdIns(4,5)P(2), is targeted to focal adhesions by an association with talin. PIPKI gamma 661 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)P(2) at focal adhesions.

Asunto(s)

Adhesiones Focales; Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo; Talina/metabolismo; Actinas/metabolismo; Animales; Sitios de Unión; Línea Celular; Membrana Celular/enzimología; Membrana Celular/metabolismo; Quinasa 1 de Adhesión Focal; Proteína-Tirosina Quinasas de Adhesión Focal; Humanos; Cadenas beta de Integrinas/metabolismo; Isoenzimas/química; Isoenzimas/genética; Isoenzimas/metabolismo; Ratones; Fosfatidilinositol 4,5-Difosfato/metabolismo; Fosfotransferasas (Aceptor de Grupo Alcohol)/química; Fosfotransferasas (Aceptor de Grupo Alcohol)/genética; Unión Proteica; Proteínas Tirosina Quinasas/metabolismo; Ratas; Proteínas Recombinantes de Fusión/química; Proteínas Recombinantes de Fusión/genética; Proteínas Recombinantes de Fusión/metabolismo; Talina/química; Vinculina/metabolismo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Talina / Fosfotransferasas (Aceptor de Grupo Alcohol) / Adhesiones Focales Límite: Animals / Humans Idioma: En Revista: Nature Año: 2002 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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