Focal adhesion kinase modulates cell adhesion strengthening via integrin activation

Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the e...

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Bibliographic Details
Published in:Molecular biology of the cell 2009-05, Vol.20 (9), p.2508-2519
Main Authors: Michael, Kristin E, Dumbauld, David W, Burns, Kellie L, Hanks, Steven K, García, Andrés J
Format: Article
Language:English
Subjects:
Animals
Biomechanical Phenomena - drug effects
Cell Adhesion - drug effects
Fibroblasts - cytology
Fibroblasts - drug effects
Fibroblasts - enzymology
Fibronectins - metabolism
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Gene Knockdown Techniques
Humans
Integrin alpha5beta1 - metabolism
Integrins - metabolism
Kinetics
Mice
Phosphorylation - drug effects
Phosphotyrosine - metabolism
Protein Binding - drug effects
Solubility - drug effects
Talin - metabolism
Tetracycline - pharmacology
Vinculin - metabolism
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Summary:Focal adhesion kinase (FAK) is an essential nonreceptor tyrosine kinase regulating cell migration, adhesive signaling, and mechanosensing. Using FAK-null cells expressing FAK under an inducible promoter, we demonstrate that FAK regulates the time-dependent generation of adhesive forces. During the early stages of adhesion, FAK expression in FAK-null cells enhances integrin activation to promote integrin binding and, hence, the adhesion strengthening rate. Importantly, FAK expression regulated integrin activation, and talin was required for the FAK-dependent effects. A role for FAK in integrin activation was confirmed in human fibroblasts with knocked-down FAK expression. The FAK autophosphorylation Y397 site was required for the enhancements in adhesion strengthening and integrin-binding responses. This work demonstrates a novel role for FAK in integrin activation and the time-dependent generation of cell-ECM forces.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E08-01-0076