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Science. 2010 Jan 15;327(5963):340-3. doi: 10.1126/science.1174779.

G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin "outside-in" signaling.

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


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) Galpha13 directly bound to the integrin beta3 cytoplasmic domain and that Galpha13-integrin interaction was promoted by ligand binding to the integrin alphaIIbbeta3 and by guanosine triphosphate (GTP) loading of Galpha13. Interference of Galpha13 expression or a myristoylated fragment of Galpha13 that inhibited interaction of alphaIIbbeta3 with Galpha13 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 Galpha13-coupled receptors that provide a mechanism for dynamic regulation of RhoA.

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