Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover.
Focal adhesion kinase (FAK) is activated and localized at focal adhesions upon cell adhesion to extracellular matrices. Cells lacking FAK show increased focal adhesion number and decreased cell migration, functions that are regulated by the small GTPase Rho. We now report that fibroblasts from FAK-/- mice failed to transiently inhibit Rho activity when plated on fibronectin. Re-expression of FAK restored normal Rho regulation. Turnover of focal adhesions correlated inversely with Rho activity. The presence or absence of FAK was mimicked by inhibiting or activating Rho, respectively. These data suggest that loss of FAK resulting in constitutive activation of Rho and inhibition of focal adhesion turnover can account for deficiencies in cell migration and embryonic lethality of the FAK knockout.
Ren
X D
XD
Departments of Vascular Biology and Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Kiosses
W B
WB
Sieg
D J
DJ
Otey
C A
CA
Schlaepfer
D D
DD
Schwartz
M A
MA
D000818:Animals; D002465:Cell Movement; D048429:Cell Size; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D004789:Enzyme Activation; D005347:Fibroblasts; D005353:Fibronectins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005353:Fibronectins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020741:rho GTP-Binding Proteins