Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex

Nat Cell Biol. 2007 Sep;9(9):1046-56. doi: 10.1038/ncb1626. Epub 2007 Aug 26.


Networks of actin filaments, controlled by the Arp2/3 complex, drive membrane protrusion during cell migration. How integrins signal to the Arp2/3 complex is not well understood. Here, we show that focal adhesion kinase (FAK) and the Arp2/3 complex associate and colocalize at transient structures formed early after adhesion. Nascent lamellipodia, which originate at these structures, do not form in FAK-deficient cells, or in cells in which FAK mutants cannot be autophosphorylated after integrin engagement. The FERM domain of FAK binds directly to Arp3 and can enhance Arp2/3-dependent actin polymerization. Critically, Arp2/3 is not bound when FAK is phosphorylated on Tyr 397. Interfering peptides and FERM-domain point mutants show that FAK binding to Arp2/3 controls protrusive lamellipodia formation and cell spreading. This establishes a new function for the FAK FERM domain in forming a phosphorylation-regulated complex with Arp2/3, linking integrin signalling directly with the actin polymerization machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • Focal Adhesion Protein-Tyrosine Kinases / chemistry*
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Integrins / metabolism
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary*
  • Pseudopodia / metabolism
  • Stress Fibers / metabolism
  • Tyrosine / metabolism
  • Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism


  • Actin-Related Protein 2-3 Complex
  • Actins
  • Integrins
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Tyrosine
  • Focal Adhesion Protein-Tyrosine Kinases