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Molecular and Cellular Biology, January 1999, p. 21-30, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Regulation of the MEF2 Family of Transcription Factors by p38dagger

Ming Zhao,1 Liguo New,1 Vladimir V. Kravchenko,1 Yutaka Kato,1 Hermann Gram,2 Franco di Padova,2 Eric N. Olson,3 Richard J. Ulevitch,1 and Jiahuai Han1,*

Department of Immunology, The Scripps Research Institute, La Jolla, California 920371; Novartis Pharma AG, CH-4002 Basel, Switzerland2; and Department of Molecular Biology and Oncology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 752353

Received 13 August 1998/Accepted 24 September 1998

Members of the MEF2 family of transcription factors bind as homo- and heterodimers to the MEF2 site found in the promoter regions of numerous muscle-specific, growth- or stress-induced genes. We showed previously that the transactivation activity of MEF2C is stimulated by p38 mitogen-activated protein (MAP) kinase. In this study, we examined the potential role of the p38 MAP kinase pathway in regulating the other MEF2 family members. We found that MEF2A, but not MEF2B or MEF2D, is a substrate for p38. Among the four p38 group members, p38 is the most potent kinase for MEF2A. Threonines 312 and 319 within the transcription activation domain of MEF2A are the regulatory sites phosphorylated by p38. Phosphorylation of MEF2A in a MEF2A-MEF2D heterodimer enhances MEF2-dependent gene expression. These results demonstrate that the MAP kinase signaling pathway can discriminate between different MEF2 isoforms and can regulate MEF2-dependent genes through posttranslational activation of preexisting MEF2 protein.

* Corresponding author. Mailing address: Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037. Phone: (619) 784-8704. Fax: (619) 784-8227. E-mail: jhan{at}scripps.edu.

dagger Publication no. 11506-IMM from the Department of Immunology of The Scripps Research Institute.

Molecular and Cellular Biology, January 1999, p. 21-30, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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