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Science 327 (5963): 340-343

Copyright © 2010 by the American Association for the Advancement of Science

G Protein Subunit G{alpha}13 Binds to Integrin {alpha}IIbβ3 and Mediates Integrin "Outside-In" Signaling

Haixia Gong, Bo Shen, Panagiotis Flevaris, Christina Chow, Stephen C.-T. Lam, Tatyana A. Voyno-Yasenetskaya, Tohru Kozasa, Xiaoping Du*

Abstract: 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) G{alpha}13 directly bound to the integrin β3 cytoplasmic domain and that G{alpha}13-integrin interaction was promoted by ligand binding to the integrin {alpha}IIbβ3 and by guanosine triphosphate (GTP) loading of G{alpha}13. Interference of G{alpha}13 expression or a myristoylated fragment of G{alpha}13 that inhibited interaction of {alpha}IIbβ3 with G{alpha}13 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 G{alpha}13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.

Department of Pharmacology, University of Illinois at Chicago, 835 South Wolcott Avenue, Room E403, Chicago, IL 60612, USA.

* To whom correspondence should be addressed. E-mail: xdu{at}uic.edu

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