Phosphorylation Motifs Regulating the Stability and Function of Myocyte Enhancer Factor 2A

The phosphorylation status of the myocyte enhancer factor 2 (MEF2) transcriptional regulator is a critical determinant of its tissue-specific functions. However, due to the complexity of its phosphorylation pattern in vivo, a systematic inventory of MEF2A phosphorylation sites in mammalian cells has...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-04, Vol.278 (17), p.15297-15303
Main Authors: Cox, David M., Du, Min, Marback, Michaela, Yang, Eric C.C., Chan, Joseph, Siu, K.W. Michael, McDermott, John C.
Format: Article
Language:English
Subjects:
Amino Acid Motifs - physiology
Animals
Binding Sites
Casein Kinase II
Chromatography, Affinity
Conserved Sequence - physiology
COS Cells
DNA-Binding Proteins - isolation & purification
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Gene Expression Regulation
HeLa Cells
Humans
MADS Domain Proteins
MAP Kinase Signaling System
Mass Spectrometry
MEF2 Transcription Factors
Mitogen-Activated Protein Kinases - metabolism
Myogenic Regulatory Factors
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Protein-Serine-Threonine Kinases - metabolism
Sequence Alignment
Transcription Factors - isolation & purification
Transcription Factors - metabolism
Transcription Factors - physiology
Transfection
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Summary:The phosphorylation status of the myocyte enhancer factor 2 (MEF2) transcriptional regulator is a critical determinant of its tissue-specific functions. However, due to the complexity of its phosphorylation pattern in vivo, a systematic inventory of MEF2A phosphorylation sites in mammalian cells has been difficult to obtain. We employed modern affinity purification techniques, combined with mass spectrometry, to identify several novel MEF2 phosphoacceptor sites. These include an evolutionarily conserved KSP motif, which we show is important in regulating the stability and function of MEF2A. Also, an indirect pathway in which a protein kinase casein kinase 2 phosphoacceptor site is phosphorylated by activation of p38 MAPK signaling was documented. Together, these findings identify several novel aspects of MEF2 regulation that may prove important in the control of gene expression in neuronal and muscle cells.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M211312200