G Protein Subunit Gα13 Binds to Integrin αIIbβ3 and Mediates Integrin “Outside-In” Signaling

Science  15 Jan 2010:
Vol. 327, Issue 5963, pp. 340-343
DOI: 10.1126/science.1174779

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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.

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