title: FAK promotes organization of fibronectin matrix and fibrillar adhesions.
abstract: Targeted disruption of the focal adhesion kinase (FAK) gene in mice is lethal at embryonic day 8.5 (E8.5). Vascular defects in FAK-/- mice result from the inability of FAK-deficient endothelial cells to organize themselves into vascular network. We found that, although fibronectin (FN) levels were similar, its organization was less fibrillar in both FAK-/- endothelial cells and mesoderm of E8.5 FAK-/- embryos, as well as in mouse embryonic fibroblasts isolated from mutant embryos. FAK catalytic activity, proline-rich domains, and location in focal contacts were all required for proper allocation and patterning of FN matrix. Cells lacking FAK in focal adhesions fail to translocate supramolecular complexes of integrin-bound FN and focal adhesion proteins along actin filaments to form mature fibrillar adhesions. Taken together, our data suggest that proper FN allocation and organization are dependent on FAK-mediated remodeling of focal adhesions.
authors.affiliation: Department of Stomatology, University of California San Francisco, San Francisco, California 94143, USA. ilic@itsa.ucsf.edu
authors.forename: Dusko
authors.initials: D
authors.lastname: Ilić
authors.forename: Branka
authors.initials: B
authors.lastname: Kovacic
authors.forename: Kohei
authors.initials: K
authors.lastname: Johkura
authors.forename: David D
authors.initials: DD
authors.lastname: Schlaepfer
authors.forename: Nenad
authors.initials: N
authors.lastname: Tomasević
authors.forename: Qin
authors.initials: Q
authors.lastname: Han
authors.forename: Jae-Beom
authors.initials: JB
authors.lastname: Kim
authors.forename: Kyle
authors.initials: K
authors.lastname: Howerton
authors.forename: Clark
authors.initials: C
authors.lastname: Baumbusch
authors.forename: Naoko
authors.initials: N
authors.lastname: Ogiwara
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Streblow
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Paul
authors.initials: P
authors.lastname: Dazin
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shino
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Caroline H
authors.initials: CH
authors.lastname: Damsky
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005353:Fibronectins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse