anisomycin and Carcinoma--Embryonal

Retinoic acid induces P19 mouse embryonal carcinoma cells to differentiate to endoderm and increases expression of the heterotrimeric G-protein subunits Galpha12 and Galpha13. 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 Galpha12 and Galpha13 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 Galpha12 or Galpha13 obligate for retinoic acid-induced differentiation.

Topics: Animals; Anisomycin; Calcium-Calmodulin-Dependent Protein Kinases; Carcinoma, Embryonal; Cell Differentiation; Embryonic and Fetal Development; Enzyme Activation; GTP-Binding Proteins; JNK Mitogen-Activated Protein Kinases; Lewis X Antigen; Mice; Mitogen-Activated Protein Kinases; Tretinoin