title: FAK potentiates Rac1 activation and localization to matrix adhesion sites: a role for betaPIX.
abstract: FAK, a cytoplasmic protein tyrosine kinase, is activated and localized to focal adhesions upon cell attachment to extracellular matrix. FAK null cells spread poorly and exhibit altered focal adhesion turnover. Rac1 is a member of the Rho-family GTPases that promotes membrane ruffling, leading edge extension, and cell spreading. We investigated the activation and subcellular location of Rac1 in FAK null and FAK reexpressing fibroblasts. FAK reexpressers had a more robust pattern of Rac1 activation after cell adhesion to fibronectin than the FAK null cells. Translocation of Rac1 to focal adhesions was observed in FAK reexpressers, but seldom in FAK null cells. Experiments with constitutively active L61Rac1 and dominant negative N17Rac1 indicated that the activation state of Rac1 regulated its localization to focal adhesions. We demonstrated that FAK tyrosine-phosphorylated betaPIX and thereby increased its binding to Rac1. In addition, betaPIX facilitated the targeting of activated Rac1 to focal adhesions and the efficiency of cell spreading. These data indicate that FAK has a role in the activation and focal adhesion translocation of Rac1 through the tyrosine phosphorylation of betaPIX.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Fumin
authors.initials: F
authors.lastname: Chang
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lemmon
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Romer
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D064067:Rho Guanine Nucleotide Exchange Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C576607:Arhgef7 protein, mouse; D018797:Cell Cycle Proteins; D005353:Fibronectins; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020830:rac1 GTP-Binding Protein