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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.
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
May 1997,
The American journal of physiology,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
March 2006,
Journal of neurochemistry,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
January 1996,
The Journal of clinical investigation,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
June 2001,
Journal of immunology (Baltimore, Md. : 1950),
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
April 2000,
Sheng li ke xue jin zhan [Progress in physiology],
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
January 2002,
Critical care medicine,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
January 2002,
Critical care medicine,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
February 2008,
Experimental cell research,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
August 2003,
FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Q Chen, and
M S Kinch, and
T H Lin, and
K Burridge, and
R L Juliano
June 2002,
American journal of respiratory cell and molecular biology,
