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

Abstract:

: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.

journal_name

Nature

journal_title

Nature

authors

Ling K,Doughman RL,Firestone AJ,Bunce MW,Anderson RA

doi

10.1038/nature01082

keywords:

subject

Has Abstract

pub_date

2002-11-07 00:00:00

pages

89-93

issue

6911

eissn

0028-0836

issn

1476-4687

pii

nature01082

journal_volume

420

pub_type

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