DOI: 10.1083/jcb.147.3.611. Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase

Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase

10.1083/jcb.147.3.611

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

The mitogen-activated protein (MAP) kinase pathway is a critical regulator of cell growth, migration, and differentiation. Growth factor activation of MAP kinase in NIH 3T3 cells is strongly dependent upon integrin-mediated adhesion, an effect that contributes to the anchorage dependence of normal cell growth. We now show that expression of constructs that constitutively activate focal adhesion kinase (FAK) rescued the defect in serum activation of MAP kinase in suspended cells without directly activating MAP kinase. Dominant negative FAK blocked both the rescue of suspended cells by the activated construct and the serum activation of MAP kinase in adherent cells. MAP kinase in FAK−/− mouse embryo fibroblasts was adhesion-insensitive, and reexpression of FAK restored its adhesion dependence. MAP kinase activity in ras-transformed cells is still decreased in suspension, but expression of constructs that constitutively activate FAK enhanced their anchorage-independent growth without increasing adherent growth. V-src, which activates both Ras and FAK, induced MAP kinase activation that was insensitive to loss of adhesion, and that was blocked by a dominant negative FAK. These results demonstrate that FAK mediates the integrin requirement for serum activation of MAP kinase in normal cells, and that bypassing this mechanism contributes to anchorage-independent growth in transformed cells.

Bibliography

Renshaw, M. W., Price, L. S., & Schwartz, M. A. (1999). Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase. The Journal of Cell Biology, 147(3), 611â618.

Authors 3

Mark W. Renshaw (first)
Leo S. Price (additional)
Martin Alexander Schwartz (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:45 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 9:09 p.m.)
Indexed	1 month, 3 weeks ago (July 8, 2025, 7:29 a.m.)
Issued	25 years, 10 months ago (Nov. 1, 1999)
Published	25 years, 10 months ago (Nov. 1, 1999)
Published Online	25 years, 10 months ago (Nov. 1, 1999)
Published Print	25 years, 10 months ago (Nov. 1, 1999)

Funders 0

None

BibTeX

@article{Renshaw_1999, title={Focal Adhesion Kinase Mediates the Integrin Signaling Requirement for Growth Factor Activation of Map Kinase}, volume={147}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.147.3.611}, DOI={10.1083/jcb.147.3.611}, number={3}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Renshaw, Mark W. and Price, Leo S. and Schwartz, Martin Alexander}, year={1999}, month=nov, pages={611–618} }

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