c-Jun amino-terminal kinase is regulated by Galpha12/Galpha13 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 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.
Jho
E H
EH
Department of Molecular Pharmacology, Diabetes & Metabolic Diseases Research Program, University Medical Center, State University of New York, Stony Brook, New York 11794-8651, USA.
Davis
R J
RJ
Malbon
C C
CC
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*
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