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A critical role for cortactin phosphorylation by Abl-family kinases in PDGF-induced dorsal-wave formation

Scott N Boyle1, Gregory A Michaud, Barry Schweitzer

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.

Current Biology : CB
|February 20, 2007
PubMed

Insights

Abl-family kinases phosphorylate cortactin, a protein crucial for cell motility and cytoskeletal rearrangement. This interaction is essential for platelet-derived growth factor-induced cell responses, revealing a new signaling pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Abl-family tyrosine kinases regulate cell morphogenesis and migration.
  • Existing identified substrates do not fully explain Abl-kinase downstream effects on cytoskeletal structure.

Purpose of the Study:

  • Identify novel substrates of Abl and Abl-related gene (Arg) nonreceptor tyrosine kinases.
  • Investigate the role of cortactin phosphorylation by Abl/Arg in platelet-derived growth factor (PDGF)-induced cellular responses.

Main Methods:

  • Human protein microarray to identify novel kinase substrates.
  • In vitro kinase assays to assess binding and phosphorylation.
  • Analysis of PDGF-induced cellular responses in fibroblasts.

Main Results:

  • Cortactin identified as a novel substrate of Abl and Arg kinases.
  • Abl and Arg kinases exhibit higher affinity for cortactin compared to Src-family kinases.
  • PDGF-induced cortactin phosphorylation on three tyrosine residues is dependent on Abl or Arg.
  • Abl/Arg-mediated cortactin phosphorylation is required for PDGF-induced dorsal waves and lamellipodial protrusion.

Conclusions:

  • Abl-family kinases directly target cortactin, a key regulator of actin dynamics.
  • Cortactin phosphorylation by Abl/Arg is a critical step in PDGF-mediated cytoskeletal rearrangements and cell motility.
  • This study uncovers a novel signaling mechanism involving Abl-family kinases and cortactin in cellular responses.

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