DOI: 10.1083/jcb.136.6.1385. Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts

Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts

10.1083/jcb.136.6.1385

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Integrin-mediated cell adhesion causes activation of MAP kinases and increased tyrosine phosphorylation of focal adhesion kinase (FAK). Autophosphorylation of FAK leads to the binding of SH2-domain proteins including Src-family kinases and the Grb2–Sos complex. Since Grb2–Sos is a key regulator of the Ras signal transduction pathway, one plausible hypothesis has been that integrin-mediated tyrosine phosphorylation of FAK leads to activation of the Ras cascade and ultimately to mitogen activated protein (MAP) kinase activation. Thus, in this scenario FAK would serve as an upstream regulator of MAP kinase activity. However, in this report we present several lines of evidence showing that integrin-mediated MAP kinase activity in fibroblasts is independent of FAK. First, a β1 integrin subunit deletion mutant affecting the putative FAK binding site supports activation of MAP kinase in adhering fibroblasts but not tyrosine phosphorylation of FAK. Second, fibroblast adhesion to bacterially expressed fragments of fibronectin demonstrates that robust activation of MAP kinase can precede tyrosine phosphorylation of FAK. Finally, we have used FRNK, the noncatalytic COOH-terminal domain of FAK, as a dominant negative inhibitor of FAK autophosphorylation and of tyrosine phosphorylation of focal contacts. Using retroviral infection, we demonstrate that levels of FRNK expression sufficient to completely block FAK tyrosine phosphorylation were without effect on integrin-mediated activation of MAP kinase. These results strongly suggest that integrin-mediated activation of MAP kinase is independent of FAK and indicate the probable existence of at least two distinct integrin signaling pathways in fibroblasts.

Bibliography

Lin, T. H., Aplin, A. E., Shen, Y., Chen, Q., Schaller, M., Romer, L., Aukhil, I., & Juliano, R. L. (1997). Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts. The Journal of Cell Biology, 136(6), 1385â1395.

Authors 8

Tsung H. Lin (first)
Andrew E. Aplin (additional)
Yu Shen (additional)
Qiming Chen (additional)
Michael Schaller (additional)
Lewis Romer (additional)
Ikramuddin Aukhil (additional)
R.L. Juliano (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:47 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 2:41 a.m.)
Indexed	1 month, 3 weeks ago (July 1, 2025, 9:48 a.m.)
Issued	28 years, 5 months ago (March 24, 1997)
Published	28 years, 5 months ago (March 24, 1997)
Published Online	28 years, 5 months ago (March 24, 1997)
Published Print	28 years, 5 months ago (March 24, 1997)

Funders 0

None

BibTeX

@article{Lin_1997, title={Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts}, volume={136}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.136.6.1385}, DOI={10.1083/jcb.136.6.1385}, number={6}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Lin, Tsung H. and Aplin, Andrew E. and Shen, Yu and Chen, Qiming and Schaller, Michael and Romer, Lewis and Aukhil, Ikramuddin and Juliano, R.L.}, year={1997}, month=mar, pages={1385–1395} }

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