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 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.
Michael
Kristin E
KE
Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Dumbauld
David W
DW
Burns
Kellie L
KL
Hanks
Steven K
SK
García
Andrés J
AJ
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005353:Fibronectins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D016608:Talin / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology; D016596:Vinculin / Q000378:metabolism
D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins; D016608:Talin; D016596:Vinculin; D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D013752:Tetracycline