Differential regulation of Rho GTPases by β1 and β3 integrins: The role of an extracellular domain of integrin in intracellular signaling

Integrins mediate cell adhesion and signal transduction at focal adhesions. Here we investigate the roles of integrin β subunits in the regulation of actin cytoskeletal structure and the activities of Rho and Rac. The overexpression of β3 integrin in Chinese hamster ovary cells enhances Rho activity and stress fiber formation, whereas the overexpression of β1 integrin increases Rac activity and lamellipodia formation. The overexpression of a mutant β1-3-1 integrin, in which the extracellular I-domain-like sequence of β1 integrin has been replaced with the corresponding sequence of β3 integrin, also enhances Rho activity and the formation of stress fibers. Our results demonstrate that β1 and β3 integrins differentially regulate the activities of Rho family GTPases and that the extracellular domains of integrin β subunits play a critical role in transducing the extracellular ligand-binding information into specific intracellular signaling events.