c-Jun amino-terminal kinase is regulated by G alpha(12)/G alpha(13) 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 G alpha(12) and G alpha(13). Retinoic acid was found to induce differentiation and sustained activation of c-Jun amino-terminal kinase, but not of ERK1,S or of p38 mitogen-activated protein kinases. Much like retinoic acid, expression of constitutively active forms of G alpha(12) and G alpha(13) 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 G alpha(12) or G alpha(13) obligate for re0inoie acid-induced differentiation.