Focal Adhesion Kinase Modulates Cell Adhesion Strengthening via Integrin Activation |
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Authors: | Kristin E. Michael, David W. Dumbauld, Kellie L. Burns, Steven K. Hanks, Andr s J. Garcí a |
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Affiliation: | Kristin E. Michael, David W. Dumbauld, Kellie L. Burns, Steven K. Hanks, and Andrés J. García |
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Abstract: | 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. |
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