title: c-Jun amino-terminal kinase is regulated by Galpha12/Galpha13 and obligate for differentiation of P19 embryonal carcinoma cells by retinoic acid.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology, Diabetes & Metabolic Diseases Research Program, University Medical Center, State University of New York, Stony Brook, New York 11794-8651, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Jho
authors.forename: R J
authors.initials: RJ
authors.lastname: Davis
authors.forename: C C
authors.initials: CC
authors.lastname: Malbon
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018236:Carcinoma, Embryonal / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D005314:Embryonic and Fetal Development; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D016256:Lewis X Antigen; D014212:Tretinoin; D000841:Anisomycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins