Regulation of the MEF2 family of transcription factors by p38.
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.
Zhao
M
M
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
New
L
L
Kravchenko
V V
VV
Kato
Y
Y
Gram
H
H
di Padova
F
F
Olson
E N
EN
Ulevitch
R J
RJ
Han
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002384:Catalysis; D002461:Cell Line, Transformed; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors; D010766:Phosphorylation; D013379:Substrate Specificity; D013912:Threonine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; C578038:MEF2B protein, human; C578040:MEF2C protein, human; C578043:MEF2D protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D013912:Threonine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases