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J Biol Chem. 1994 Oct 28;269(43):26602-5.

Integrin-mediated cell adhesion activates mitogen-activated protein kinases.

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  • 1Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599.

Abstract

Integrins can function as signal-transducing receptors capable of modulating cell growth and gene expression (Juliano, R. L., and Haskill, S. (1993) J. Cell Biol. 120, 577-585; Hynes, R. O. (1992) Cell 69, 11-25). An early event in integrin signaling in fibroblasts and other cells involves activation of pp125FAK, a cytoplasmic tyrosine kinase (Hanks, S. K., Calalb, M. B., Harper, M. C., and Patel, S. K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 8487-8491; Schaller, M. D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B., and Parsons, J. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5192-5196). Here we report a novel aspect of integrin-mediated signal transduction. We demonstrate that adhesion of cells to substrata coated with extracellular matrix proteins, or with a synthetic peptide containing the RGD sequence, can cause activation of mitogen-activated protein (MAP) kinases in 3T3 or REF52 fibroblasts. Activation of MAP kinases seems to depend on integrin engagement rather than simply on cell attachment. Thus, MAP kinases are activated when cells adhere to substrata coated with the integrin ligands fibronectin or laminin, but not when cells adhere to poly-D-lysine, a nonspecific adhesion-promoting polypeptide. Treatment of cells with cytochalasin D, an inhibitor of actin microfilament assembly, almost completely blocks adhesion-induced MAP kinase activation, indicating a critical role for the cytoskeleton. In REF52 cells, we have observed that activation of MAP kinases is accompanied by redistribution of the protein to the nucleus, suggesting that the activated kinases may impinge on factors regulating gene expression. Thus, integrin-mediated cell adhesion seems a sufficient stimulus to cause activation and nuclear translocation of MAP kinases. This may have important implications for the regulation of cell growth and differentiation by the extracellular matrix.

PMID:
7929388
[PubMed - indexed for MEDLINE]
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