c-Jun amino-terminal kinase is regulated by Gα¹²/Gα¹³ and obligate for differentiation of P19 embryonal carcinoma cells by retinoic acid

Retinoic acid induces P19 mouse embryonal carcinoma cells to differentiate to endoderm and increases expression of the heterotrimeric G- protein subunits Gα¹² and Gα¹³. Retinoic acid was found to induce differentiation and sustained activation of c-Jun amino-terminal kinase, but not of ERK1,2 or of p38 mitogen-activated protein kinases. Much like retinoic acid, expression of constitutively active forms of Gα¹² and Gα¹³ induced differentiation and constitutive activation of c-Jun amino-terminal kinase. Expression of the dominant negative form of c-Jun amino-terminal kinase 1 blocked both the activation of c-Jun amino-terminal kinase and the induction of endodermal differentiation in the presence of retinoic acid. These data implicate c-Jun amino-terminal kinase as a downstream element of activation of Gα¹² or Gα¹³ obligate for retinoic acid-induced differentiation.