Steven Hanks
Last active: 1/20/2015

Focal adhesion kinase-dependent regulation of adhesive forces involves vinculin recruitment to focal adhesions.

Dumbauld DW, Michael KE, Hanks SK, GarcĂ­a AJ
Biol Cell. 2010 102 (4): 203-213

PMID: 19883375 · PMCID: PMC4915345 · DOI:10.1042/BC20090104

BACKGROUND INFORMATION - FAK (focal adhesion kinase), an essential non-receptor tyrosine kinase, plays pivotal roles in migratory responses, adhesive signalling and mechanotransduction. FAK-dependent regulation of cell migration involves focal adhesion turnover dynamics as well as actin cytoskeleton polymerization and lamellipodia protrusion. Whereas roles for FAK in migratory and mechanosensing responses have been established, the contribution of FAK to the generation of adhesive forces is not well understood.

RESULTS - Using FAK-null cells expressing wild-type and mutant FAK under an inducible tetracycline promoter, we analysed the role of FAK in the generation of steady-state adhesive forces using micropatterned substrates and a hydrodynamic adhesion assay. FAK expression reduced steady-state strength by 30% compared with FAK-null cells. FAK expression reduced VCL (vinculin) localization to focal adhesions by 35% independently of changes in integrin binding and localization of talin and paxillin. RNAi (RNA interference) knock-down of VCL abrogated the FAK-dependent differences in adhesive forces. FAK-dependent changes in VCL localization and adhesive forces were confirmed in human primary fibroblasts with FAK knocked down by RNAi. The autophosphorylation Tyr-397 and kinase domain Tyr-576/Tyr-577 sites were differentially required for FAK-mediated adhesive responses.

CONCLUSIONS - We demonstrate that FAK reduces steady-state adhesion strength by modulating VCL recruitment to focal adhesions. These findings provide insights into the role of FAK in mechanical interactions between a cell and the extracellular matrix.

MeSH Terms (11)

Cell Adhesion Cells, Cultured Down-Regulation Extracellular Matrix Fibroblasts Focal Adhesion Protein-Tyrosine Kinases Focal Adhesions Gene Expression Humans Mutation Vinculin

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