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Volume 272, Number 39, Issue of September 26, 1997 pp. 24468-24474
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

c-Jun Amino-terminal Kinase Is Regulated by G₁₂/G₁₃ and Obligate for Differentiation of P19 Embryonal Carcinoma Cells by Retinoic Acid

(Received for publication, April 15, 1997, and in revised form, June 18, 1997)

Eek-Hoon Jho , Roger J. Davis ^§ and Craig C. Malbon

From the  Department of Molecular Pharmacology, Diabetes & Metabolic Diseases Research Program, University Medical Center, State University of New York, Stony Brook, New York 11794-8651 and the ^§ Program in Molecular Medicine and Howard Hughes Medical Institute, University of Massachusetts Medical Center, Worcester, Massachusetts 01605

Retinoic acid induces P19 mouse embryonal carcinoma cells to differentiate to endoderm and increases expression of the heterotrimeric G-protein subunits G₁₂ and G₁₃. 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 G₁₂ and G₁₃ 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 G₁₂ or G₁₃ obligate for retinoic acid-induced differentiation.

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