Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions

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

Research output: Contribution to journalArticle

347 Citations (Scopus)

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 1-3. Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P 2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin 4-9. The binding of talin β-integrin is strengthened by PtdIns(4,5)P 2, suggesting that the basis of focal adhesion assembly is regulated by this lipid mediator 9,10. Here we show that the type I phosphatidylinositol phosphate kinase isoform-γ 661 (PIPKIγ661), an enzyme that makes PtdIns(4,5)P 2, 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)P 2 at focal adhesions.

Original languageEnglish (US)
Pages (from-to)89-93
Number of pages5
JournalNature
Volume420
Issue number6911
DOIs
StatePublished - Nov 7 2002
Externally publishedYes

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Talin
Phosphatidylinositol Phosphates
Focal Adhesions
Phosphotransferases
Extracellular Matrix
Integrins
Protein Isoforms
Vinculin
Focal Adhesion Protein-Tyrosine Kinases
Phosphatidylinositols
Wound Healing
Tyrosine
Actins
Cell Survival
Proteins
Neoplasm Metastasis
Lipids
phosphatidylinositol 5-phosphate
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Ling, K., Doughman, R. L., Firestone, A. J., Bunce, M. W., & Anderson, R. A. (2002). Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature, 420(6911), 89-93. https://doi.org/10.1038/nature01082

Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. / Ling, Kun; Doughman, Renee L.; Firestone, Ari J.; Bunce, Matthew W.; Anderson, Richard A.

In: Nature, Vol. 420, No. 6911, 07.11.2002, p. 89-93.

Research output: Contribution to journalArticle

Ling, K, Doughman, RL, Firestone, AJ, Bunce, MW & Anderson, RA 2002, 'Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions', Nature, vol. 420, no. 6911, pp. 89-93. https://doi.org/10.1038/nature01082
Ling, Kun ; Doughman, Renee L. ; Firestone, Ari J. ; Bunce, Matthew W. ; Anderson, Richard A. / Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions. In: Nature. 2002 ; Vol. 420, No. 6911. pp. 89-93.
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