Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn.
Cellular interactions with the extracellular matrix proteins play important roles in a variety of biological processes. Recent studies suggest that integrin-mediated cell-matrix interaction can transduce biochemical signals across the plasma membrane to regulate cellular functions such as proliferation, differentiation and migration. These studies have implicated a critical role of focal adhesion kinase (FAK) in integrin-mediated signal transduction pathways. We report here that overexpression of FAK in CHO cells increased their migration on fibronectin. A mutation of the major autophosphorylation site Y397 in FAK abolished its ability to stimulate cell migration, while phosphorylation of Y397 in a kinase-defective FAK by endogenous FAK led to increased migration. We also find that the wild-type and the kinase-defective FAK were associated with Src and Fyn in CHO cells whereas the F397 mutant was not. These results directly demonstrate a functional role for FAK in integrin signaling leading to cell migration. They also provide evidence for the functional significance of FAK/Src complex formation in vivo.
Cary
L A
LA
Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Chang
J F
JF
Guan
J L
JL
D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D006224:Cricetinae; D005353:Fibronectins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005786:Gene Expression Regulation; D016391:Genes, src; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051076:Proto-Oncogene Proteins c-fyn
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051076:Proto-Oncogene Proteins c-fyn