MafA transcription factor is phosphorylated by p38 MAP kinase.
Basic-leucine zipper transcription factors of the Maf family are key regulators of various developmental and differentiation processes. We previously reported that the phosphorylation status of MafA is a critical determinant of its biological functions. Using Western blot and mass spectrometry analysis, we now show that MafA is phosphorylated by p38 MAP kinase and identify three phosphoacceptor sites: threonine 113 and threonine 57, evolutionarily conserved residues located in the transcription activating domain, and serine 272. Mutation of these residues severely impaired MafA biological activity. Furthermore, we show that p38 also phosphorylates MafB and c-Maf. Together, these findings suggest that the p38 MAP kinase pathway is a novel regulator of large Maf transcription factors.
Sii-Felice
Karine
K
UMR 146 CNRS-Institut Curie, Bâtiment 110, Centre Universitaire, 91405 Orsay Cedex, France.
Pouponnot
Celio
C
Gillet
Sylvie
S
Lecoin
Laure
L
Girault
Jean-Antoine
JA
Eychène
Alain
A
Felder-Schmittbuhl
Marie-Paule
MP
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002645:Chickens; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051257:Proto-Oncogene Proteins c-maf; D011784:Quail; D012694:Serine / Q000235:genetics; D013912:Threonine / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
D004268:DNA-Binding Proteins; C495607:MAF protein, human; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D014157:Transcription Factors; D013912:Threonine; D012694:Serine; D048051:p38 Mitogen-Activated Protein Kinases