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Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions

Author

Listed:
  • Kun Ling

    (University of Wisconsin Medical School)

  • Renee L. Doughman

    (University of Wisconsin Medical School)

  • Ari J. Firestone

    (University of Wisconsin Medical School)

  • Matthew W. Bunce

    (University of Wisconsin Medical School)

  • Richard A. Anderson

    (University of Wisconsin Medical School)

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 matrix1,2,3. Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) regulates interactions between these proteins, including the interaction of vinculin with actin and talin4,5,6,7,8,9. 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 mediator9,10. 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.

Suggested Citation

  • Kun Ling & Renee L. Doughman & Ari J. Firestone & Matthew W. Bunce & Richard A. Anderson, 2002. "Type Iγ phosphatidylinositol phosphate kinase targets and regulates focal adhesions," Nature, Nature, vol. 420(6911), pages 89-93, November.
    • Handle: RePEc:nat:nature:v:420:y:2002:i:6911:d:10.1038_nature01082
    DOI: 10.1038/nature01082
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    Cited by:

    1. Felizzi, Federico & Iber, Dagmar, 2014. "Integrin clustering as a result of local membrane deformations and local signaling feedbacks," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 408(C), pages 198-211.

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