Gα¹² and Gα¹³ mediate differentiation of P19 mouse embryonal carcinoma cells in response to retinoic acid

P19 mouse embryonal carcinoma cells can be stimulated to differentiate into endodermal-like, mesodermal-like, and neuronal-like phenotypes in response to specific morphogens. At low concentrations, retinoic acid stimulates P19 embryonal cells to differentiate to cells displaying an endodermal phenotype, whereas at higher concentrations it stimulates differentiation to neuroectoderm. The Gα¹² and Gα¹³ subunits of heterotrimeric G-proteins are expressed in the embryonal P19 cells and stimulated in response to retinoic acid as the cells differentiate to endodermal or neuroectodermal phenotypes. Suppression of the expression of either Gα¹² or Gα¹³ by antisense RNA is shown to promote cell detachment from substratum and apoptosis. Expression of the constitutively active, mutant form of Gα¹² (Q229L), in contrast, stimulates loss of the embryonal phenotype. Expression of the constitutively active form of Gα¹³ (Q226L) stimulates differentiation of the cells from embryonal to endodermal, in the absence of retinoic acid. Thus, both Gα¹² and Gα¹³ are essential to stimulation of cell differentiation by retinoic acid. Deficiency of either G∅¹² or Gα¹³ increases programmed cell death.