Phosphorylation of MafA is essential for its transcriptional and biological properties

We previously described the identification of quail MafA, a novel transcrip tion factor of the Maf bZIP (basic region leucine zipper) family, expressed in the differentiating neuroretina (NR). In the present study, we provide the first evidence that MafA is phosphorylated and that its biological prop erties strongly rely upon phosphorylation of serines 14 and 65, two residue s located in the transcriptional activating domain within a consensus for p hosphorylation by mitogen-activated protein kinases and which are conserved among Maf proteins. These residues are phosphorylated by ERK2 but not by p 38, JNK, and ERK5 in vitro. However, the contribution of the MEK/ERK pathwa y to MafA phosphorylation in vivo appears to be moderate, implicating anoth er kinase. The integrity of serine 14 and serine 65 residues is required fo r transcriptional activity, since their mutation into alanine severely impa irs MafA capacity to activate transcription. Furthermore, we show that the MafA S14A/S65A mutant displays reduced capacity to induce expression of QR1 , an NR-specific target of Maf proteins. Likewise, the integrity of serines 14 and 65 is essential for the MafA ability to stimulate expression of cry stallin genes in NR cells and to induce IVR-to-lens transdifferentiation. T hus, the MafA capacity to induce differentiation programs is dependent on i ts phosphorylation.