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

H Gong, B Shen, P Flevaris, C Chow, SCT Lam… - Science, 2010 - science.org
H Gong, B Shen, P Flevaris, C Chow, SCT Lam, TA Voyno-Yasenetskaya, T Kozasa, X Du
Science, 2010science.org
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 …
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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