Regulation of the MEF2 family of transcription factors by p38

M Zhao; L New; V V Kravchenko; Y Kato; H Gram; F di Padova; E N Olson; R J Ulevitch; J Han

doi:10.1128/MCB.19.1.21

Regulation of the MEF2 family of transcription factors by p38

Mol Cell Biol. 1999 Jan;19(1):21-30. doi: 10.1128/MCB.19.1.21.

Authors

M Zhao¹, L New, V V Kravchenko, Y Kato, H Gram, F di Padova, E N Olson, R J Ulevitch, J Han

Affiliation

¹ Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Binding Sites
CHO Cells
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Catalysis
Cell Line, Transformed
Cricetinae
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Dimerization
HeLa Cells
Humans
MADS Domain Proteins
MEF2 Transcription Factors
Mitogen-Activated Protein Kinases*
Molecular Sequence Data
Myogenic Regulatory Factors
Phosphorylation
Substrate Specificity
Threonine
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcriptional Activation
Up-Regulation
p38 Mitogen-Activated Protein Kinases

Substances

DNA-Binding Proteins
MADS Domain Proteins
MEF2 Transcription Factors
MEF2A protein, human
MEF2B protein, human
MEF2C protein, human
MEF2D protein, human
Myogenic Regulatory Factors
Transcription Factors
Threonine
Calcium-Calmodulin-Dependent Protein Kinases
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases