The amount of the heterotrimeric G protein subunit G alpha i2 decreases after 
the induction of F9 teratocarcinoma cells to become primitive endoderm in the 
presence of retinoic acid (RA). The reduction of the G alpha i2 protein in F9 
cells by antisense RNA expression was associated with (i) loss of 
receptor-mediated inhibition of adenylyl cyclase; (ii) decreased cell doubling 
time; (iii) induction of a primitive, endoderm-like phenotype in the absence of 
RA; and (iv) production of the differentiation marker tissue-type plasminogen 
activator. Expression of a constitutively active, mutant G alpha i2 blocked 
RA-induced differentiation. These data suggest the involvement of G alpha i2 in 
the control of stem cell differentiation and provide insight into the 
involvement of G proteins in growth regulation.