Activin A, a member of the TGFβ superfamily, has many physiological and developmental functions. In pancreatic β cell cultures, activin promotes cell differentiation and insulin production. The author has found activin increases gene expression of the PAX4, one of the major transcription factors determining pancreatic β cell differentiation. This effect was mediated, at least in part, by the type IB activin receptor (ALK4). Moreover, the activity of human insulin promoter–reporter system was controlled by PAX4 and its isoform PAX4 Δ(G239–P251) in a unique fashion; positively by low concentrations, and negatively by high concentrations of these proteins. And the repression activities were different between these proteins. These findings confirm the importance of activin signal transduction in pancreatic β cell development and function.
