On the role of calpain and Rho proteins in regulating integrin-induced signaling.

Integrin-induced adhesion of cells activates intracellular signaling pathways that lead to cytoskeletal reorganizations and altered cell behavior. One of the signaling molecules that is activated as a consequence of integrin-induced signaling is calpain. Much of the understanding of calpain's importance in signaling has come from the study of platelets. Studies on platelets have demonstrated that the major substrates for calpain are proteins present in the complexes of integrin, cytoskeletal proteins, and signaling molecules that form as a consequence of integrin engagement. We have now shown that calpain is also active in cultured adherent cells and that the calpain-induced cleavage of proteins in these cells is required for integrin-induced changes in cell morphology and spreading. Investigation of the mechanisms involved has revealed that calpain induces integrin-induced formation of focal adhesions and actin filament reorganizations and that it does so by inducing the activation of both Rac1 and RhoA.