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Integrin G Protein
Adhesion molecules, known as integrins, are found on the surface of cells. When integrins adhere to components of the extracellular matrix, they act as receptors and initiate signaling events within the cell. Gong et al. (p. 340) show that they do so in part by partnering with a signal-transducing protein called Gα13. Such α subunits of heterotrimeric guanine nucleotide-binding proteins are well known for transducing signals from the large class of G protein–coupled receptors, but were not known to work with integrins. Gα13 appears to interact directly with the integrin αIIbβ3 and to transmit signals that regulate cell spreading.
Integrins mediate cell adhesion to the extracellular matrix and transmit signals within the cell that stimulate cell spreading, retraction, migration, and proliferation. The mechanism of integrin outside-in signaling has been unclear. We found that the heterotrimeric guanine nucleotide–binding protein (G protein) Gα13 directly bound to the integrin β3 cytoplasmic domain and that Gα13-integrin interaction was promoted by ligand binding to the integrin αIIbβ3 and by guanosine triphosphate (GTP) loading of Gα13. Interference of Gα13 expression or a myristoylated fragment of Gα13 that inhibited interaction of αIIbβ3 with Gα13 diminished activation of protein kinase c-Src and stimulated the small guanosine triphosphatase RhoA, consequently inhibiting cell spreading and accelerating cell retraction. We conclude that integrins are noncanonical Gα13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.