G protein subunit Gα13 binds to integrin αIIbβ3 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*

*Corresponding author for this work

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Integrins mediate cell adhesion to the extracellular matrix and transmit signals witnin 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 αIIbβ 3 and by guanosine triphosphate (GTP) loading of Gα 13. 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.

Original languageEnglish (US)
Pages (from-to)340-343
Number of pages4
JournalScience
Volume327
Issue number5963
DOIs
StatePublished - Jan 15 2010

ASJC Scopus subject areas

  • General

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    Gong, H., Shen, B., Flevaris, P., Chow, C., Lam, S. C. T., Voyno-Yasenetskaya, T. A., Kozasa, T., & Du, X. (2010). G protein subunit Gα13 binds to integrin αIIbβ3 and mediates integrin "outside-in" signaling. Science, 327(5963), 340-343. https://doi.org/10.1126/science.1174779