Conformational activation of radixin by G(13) protein alpha subunit

G(13) protein, one of the heterotrimeric guanine nucleotide-binding protein s (G proteins), regulates diverse and complex cellular responses by transdu cing signals from the cell surface presumably involving more than one pathw ay. Yeast two-hybrid screening of a mouse brain cDNA library identified rad ixin, a member of the ERM family of three closely related proteins (ezrin, radixin, and moesin), as a protein that interacted with G alpha(13). Intera ction between radixin and G alpha(13) was confirmed by in vitro binding ass ay and by co-immunoprecipitation technique. Activated Ga,, induced conforma tional activation of radixin, as determined by binding of radixin to polyme rized F-actin and by immunofluorescence in intact cells. Finally, two domin ant negative mutants of radixin inhibited G alpha(13)-induced focus formati on of Rat-1 fibroblasts but did not affect Ras-induced focus formation. Our results identifying a new signaling pathway for G alpha(13) indicate that ERM proteins can be activated by and serve as effecters of heterotrimeric G proteins.