Regulation of the differentiation of teratocarcinoma cells into primitive endoderm by Gα_i2

The amount of the heterotrimeric G protein subunit Gα_i2 decreases after the induction of F9 teratocarcinoma cells to become primitive endoderm in the presence of retinoic acid (RA). The reduction of the Gα_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 Gα_i2 blocked RA-induced differentiation. These data suggest the involvement of Gα_i2 in the control of stem cell differentiation and provide insight into the involvement of G proteins in growth regulation.