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.