title: Focal adhesion kinase controls actin assembly via a FERM-mediated interaction with the Arp2/3 complex.
abstract: 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.
authors.affiliation: The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Bryan
authors.initials: B
authors.lastname: Serrels
authors.forename: Alan
authors.initials: A
authors.lastname: Serrels
authors.forename: Valerie G
authors.initials: VG
authors.lastname: Brunton
authors.forename: Mark
authors.initials: M
authors.lastname: Holt
authors.forename: Gordon W
authors.initials: GW
authors.lastname: McLean
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Gray
authors.forename: Gareth E
authors.initials: GE
authors.lastname: Jones
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Frame
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D016023:Integrins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D014443:Tyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases