Steven Hanks
Last active: 1/20/2015

A FAK/Src chimera with gain-of-function properties promotes formation of large peripheral adhesions associated with dynamic actin assembly.

Siesser PM, Meenderink LM, Ryzhova L, Michael KE, Dumbauld DW, GarcĂ­a AJ, Kaverina I, Hanks SK
Cell Motil Cytoskeleton. 2008 65 (1): 25-39

PMID: 17922492 · PMCID: PMC2387247 · DOI:10.1002/cm.20241

Formation of a complex between the tyrosine kinases FAK and Src is a key integrin-mediated signaling event implicated in cell motility, survival, and proliferation. Past studies indicate that FAK functions in the complex primarily as a "scaffold," acting to recruit and activate Src within cell/matrix adhesions. To study the cellular impact of FAK-associated Src signaling we developed a novel gain-of-function approach that involves expressing a chimeric protein with the FAK kinase domain replaced by the Src kinase domain. This FAK/Src chimera is subject to adhesion-dependent activation and promotes tyrosine phosphorylation of p130Cas and paxillin to higher steady-state levels than is achieved by wild-type FAK. When expressed in FAK -/- mouse embryo fibroblasts, the FAK/Src chimera resulted in a striking cellular phenotype characterized by unusual large peripheral adhesions, enhanced adhesive strength, and greatly reduced motility. Live cell imaging of the chimera-expressing FAK -/- cells provided evidence that the large peripheral adhesions are associated with a dynamic actin assembly process that is sensitive to a Src-selective inhibitor. These findings suggest that FAK-associated Src kinase activity has the capacity to promote adhesion integrity and actin assembly.

MeSH Terms (11)

Actins Animals Cells, Cultured Focal Adhesion Kinase 1 Focal Adhesions Genes, src Mice Phenotype Proto-Oncogene Proteins pp60(c-src) Recombinant Fusion Proteins Signal Transduction

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