Tyrosine phosphorylation of type Iγ phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch

Kun Ling, Renee L. Doughman, Vidhya V. Iyer, Ari J. Firestone, Shawn F. Bairstow, Deane F. Mosher, Michael D. Schaller, Richard A. Anderson

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Engagement of integrin receptors with the extracellular matrix induces the formation of focal adhesions (FAs). Dynamic regulation of FAs is necessary for cells to polarize and migrate. Key interactions between FA scaffolding and signaling proteins are dependent on tyrosine phosphorylation. However, the precise role of tyrosine phosphorylation in FA development and maturation is poorly defined. Here, we show that phosphorylation of type Iγ phosphatidylinositol phosphate kinase (PIPKIγ661) on tyrosine 644 (Y644) is critical for its interaction with talin, and consequently, localization to FAs. PIPKIγ661 is specifically phosphorylated on Y644 by Src. Phosphorylation is regulated by focal adhesion kinase, which enhances the association between PIPKIγ661 and Src. The phosphorylation of Y644 results in an ∼15-fold increase in binding affinity to the talin head domain and blocks β-integrin binding to talin. This defines a novel phosphotyrosine-binding site on the talin F3 domain and a "molecular switch" for talin binding between PIPKIγ661 and β-integrin that may regulate dynamic FA turnover.

Original languageEnglish (US)
Pages (from-to)1339-1349
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number6
DOIs
StatePublished - Dec 22 2003

Keywords

  • FAK
  • Focal adhesion
  • PIPKIγ661
  • Phosphotyrosine-binding domain
  • β-integrin

ASJC Scopus subject areas

  • Cell Biology

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    Ling, K., Doughman, R. L., Iyer, V. V., Firestone, A. J., Bairstow, S. F., Mosher, D. F., Schaller, M. D., & Anderson, R. A. (2003). Tyrosine phosphorylation of type Iγ phosphatidylinositol phosphate kinase by Src regulates an integrin-talin switch. Journal of Cell Biology, 163(6), 1339-1349. https://doi.org/10.1083/jcb.200310067