ERK1/2 is a negative regulator of homeodomain protein Arix/Phox2a.

The homeodomain protein Arix/Phox2a plays a role in the development and maintenance of the noradrenergic cell type by regulating the transcription of genes involved in the biosynthesis and metabolism of noradrenaline. Previous work has shown that Arix/Phox2a is a phosphoprotein, and the phosphorylated form of Arix/Phox2a exhibits poorer DNA-binding activity than does the dephosphorylated form. Here, we demonstrate that Arix/Phox2a is phosphorylated by extracellular signal-related kinase (ERK)1/2 at two sites within the N-terminal transactivation domain.