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

Kun Ling1, Renee L Doughman, Vidhya V Iyer

  • 1Department of Pharmacology, Program in Molecular and Cellular Pharmacology, University of Wisconsin Medical School, Madison, WI 53706, USA.

The Journal of Cell Biology
|December 24, 2003
PubMed

Insights

Phosphorylation of PIPKIgamma661 on tyrosine 644 by Src is critical for focal adhesion (FA) localization and talin interaction. This phosphorylation acts as a molecular switch, regulating FA dynamics and cell migration.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Focal adhesions (FAs) are crucial for cell polarization and migration.
  • Tyrosine phosphorylation regulates key interactions within FAs, but its role in FA maturation is unclear.

Purpose of the Study:

  • To investigate the role of tyrosine phosphorylation in focal adhesion development and maturation.
  • To elucidate the specific function of PIPKIgamma661 phosphorylation in FA dynamics.

Main Methods:

  • Investigated the interaction between PIPKIgamma661 and talin using biochemical assays.
  • Utilized Src and focal adhesion kinase in phosphorylation studies.
  • Analyzed the impact of Y644 phosphorylation on binding affinities and FA localization.

Main Results:

  • Phosphorylation of PIPKIgamma661 on Y644 by Src is essential for its localization to FAs via talin interaction.
  • Focal adhesion kinase enhances PIPKIgamma661 and Src association, regulating Y644 phosphorylation.
  • Y644 phosphorylation increases PIPKIgamma661 binding to talin by 15-fold and inhibits beta-integrin binding to talin.

Conclusions:

  • Identified a novel phosphotyrosine-binding site on the talin F3 domain.
  • Demonstrated a molecular switch mechanism for talin binding, regulating FA turnover and cell migration.

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