ABSTRACT
Heterotrimeric G protein Gα13 is known to transmit G protein-coupled receptor (GPCR) signals leading to activation of RhoA and plays a role in cell migration. The mechanism underlying the role of Gα13 in cell migration, however, remains unclear. Recently we found that Gα13 interacts with the cytoplasmic domain of integrin ß3 subunits in platelets via a conserved ExE motif. Here we show that a similar direct interaction between Gα13 and the cytoplasmic domain of the integrin ß1 subunit plays a critical role in ß1-dependent cell migration. Point mutation of either glutamic acid in the Gα13-binding (767)EKE motif in ß1 or treatment with a peptide derived from the Gα13-binding sequence of ß1 abolished Gα13-ß1 interaction and inhibited ß1 integrin-dependent cell spreading and migration. We further show that the Gα13-ß1 interaction mediates ß1 integrin-dependent Src activation and transient RhoA inhibition during initial cell adhesion, which is in contrast to the role of Gα13 in mediating GPCR-dependent RhoA activation. These data indicate that Gα13 plays dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via an integrin signaling pathway. This dynamic regulation of RhoA activity is critical for cell migration on ß1 integrin ligands.