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 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.
Cox
David M
DM
Department of Biology, the Centre for Research in Mass Spectrometry, and the Department of Chemistry, York University, Toronto M3J 1P3, Canada.
Du
Min
M
Marback
Michaela
M
Yang
Eric C C
EC
Chan
Joseph
J
Siu
K W Michael
KW
McDermott
John C
JC
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D047390:Casein Kinase II; D002846:Chromatography, Affinity; D017124:Conserved Sequence / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D026161:MADS Domain Proteins; D020935:MAP Kinase Signaling System; D064326:MEF2 Transcription Factors; D013058:Mass Spectrometry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases