Cleavage of focal adhesion kinase by different proteases during Src-reguIated transformation and apoptosis - Distinct roles for calpain and caspases

Integrin-associated focal adhesion complexes provide the main adhesive link s between the cellular actin cytoskeleton and the surrounding extracellular matrix. In vitro, cells utilize a complex temporal and spatially regulated mechanism of focal adhesion assembly and disassembly required for cell mig ration. Recent studies indicate that members of both calpain and caspase pr otease families can promote Limited proteolytic cleavage of several compone nts of focal adhesions leading to disassembly of these complexes, Such mech anisms that influence cell adhesion may be deregulated under pathological c onditions characterized by increased cell motility, such as tumor invasion. v-Src-induced oncogenic transformation is associated with loss of focal ad hesion structures and transition to a less adherent, more motile phenotype, while inactivating temperature-sensitive v-Src in serum-deprived transform ed cells leads to detachment and apoptosis. In this report, we demonstrate that;v-Src-induced disassembly of focal adhesions is accompanied by calpain -dependent proteolysis of focal adhesion kinase, Furthermore, inhibitors of calpain repress v-Src-induced focal adhesion disruption, loss of substrate adhesion, and cell migration. In contrast, focal adhesion loss during deta chment and apoptosis induced after switching off temperature-sensitive v-Sr c in serum-deprived transformed cells is accompanied by caspase-mediated pr oteolysis of focal adhesion kinase. Thus, calpain and caspase differentiall y regulate focal adhesion turnover during Src-regulated cell transformation , motility, and apoptosis.