| First Author | Gong H | Year | 2010 |
| Journal | Science | Volume | 327 |
| Issue | 5963 | Pages | 340-3 |
| PubMed ID | 20075254 | Mgi Jnum | J:155860 |
| Mgi Id | MGI:4417978 | Doi | 10.1126/science.1174779 |
| Citation | Gong H, et al. (2010) G protein subunit Galpha13 binds to integrin alphaIIbbeta3 and mediates integrin 'outside-in' signaling. Science 327(5963):340-3 |
| abstractText | 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. |
