REGULATION OF THE DIFFERENTIATION OF TERATOCARCINOMA CELLS INTO PRIMITIVE ENDODERM BY G-ALPHA-I2

The amount of the heterotrimeric G protein subunit Galpha(i2) decreases after the induction of F9 teratocarcinoma cells to become primitive endoderm in the presence of retinoic acid (RA). The reduction of the Galpha(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 Galpha(i2) blocked RA-induced differentiation. These data suggest the involvement of Galpha(i2) in the control of stem cell differentiation and provide insight into the involvement of G proteins in growth regulation.