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Journal Articles
Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration
D.J. Sieg, C.R. Hauck, D.D. Schlaepfer
Journal of Cell Science 1999 112: 2677-2691;
D.J. Sieg
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C.R. Hauck
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D.D. Schlaepfer
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Summary

FAK localizes to sites of transmembrane integrin receptor clustering and facilitates intracellular signaling events. FAK-null (FAK-) fibroblasts exhibit a rounded morphology, defects in cell migration, and an elevated number of cell-substratum contact sites. Here we show that stable re-expression of epitope-tagged FAK reversed the morphological defects of the FAK- cells through the dynamic regulation of actin structures and focal contact sites in fibronectin (FN) stimulated cells. FAK re-expressing fibroblasts (clones DA2 and DP3) exhibit a characteristic fibrillar shape and display indistinguishable FN receptor-stimulated migration properties compared to normal fibroblasts. Expression of various FAK mutants in the FAK- cells showed that FAK kinase activity, the Tyr-397/SH2 domain binding site, and the first proline-rich SH3 binding region in the FAK C-terminal domain were individually needed to promote full FAK-mediated FAK- cell migration to FN whereas direct paxillin binding to FAK was not required. Expression of the FAK Phe-397 mutant did not promote FAK- cell migration and overexpression of p50(csk) in DA2 cells inhibited migration to FN suggesting that Src-family PTKs play important roles in FAK-mediated motility events. Expression of the FAK C-terminal domain, FRNK, promoted FAK dephosphorylation at Tyr-397 and potently blocked FAK-mediated cell migration. This dominant-negative effect of FRNK was reversed by a point mutation (Leu-1034 to Ser) which prevented FRNK localization to focal contact sites. Our results show that FAK functions as a key regulator of fibronectin receptor stimulated cell migration events through the recruitment of both SH2 and SH3 domain-containing signaling proteins to sites of integrin receptor clustering.

  • © 1999 by Company of Biologists
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Journal Articles
Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration
D.J. Sieg, C.R. Hauck, D.D. Schlaepfer
Journal of Cell Science 1999 112: 2677-2691;
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Journal Articles
Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration
D.J. Sieg, C.R. Hauck, D.D. Schlaepfer
Journal of Cell Science 1999 112: 2677-2691;

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