Publikation:

Required role of focal adhesion kinase (FAK) for integrin-stimulated cellmigration

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1999

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Sieg, David J.
Schlaepfer, David D.

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Published

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Journal of Cell Science. 1999, 112, pp. 2677-2691

Zusammenfassung

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 receptorstimulated 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 p50csk 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 FAKmediated 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 domaincontaining signaling proteins to sites of integrin receptor clustering.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

FAK, Fibronectin, Cell migration, Signaling

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ISO 690SIEG, David J., Christof R. HAUCK, David D. SCHLAEPFER, 1999. Required role of focal adhesion kinase (FAK) for integrin-stimulated cellmigration. In: Journal of Cell Science. 1999, 112, pp. 2677-2691
BibTex
@article{Sieg1999Requi-8080,
  year={1999},
  title={Required role of focal adhesion kinase (FAK) for integrin-stimulated cellmigration},
  volume={112},
  journal={Journal of Cell Science},
  pages={2677--2691},
  author={Sieg, David J. and Hauck, Christof R. and Schlaepfer, David D.}
}
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