Activin A increases Pax4 gene expression in pancreatic beta cell lines.
Activin A, a member of the TGFbeta superfamily, has many physiological and developmental functions. In pancreatic beta 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 beta 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 delta(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 beta cell development and function.
Ueda
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Molecular Medicine Laboratories, Yamanouchi Pharmaceutical Co, Ltd, Ibaraki, Japan. ueda@yamanouchi.co.jp
D030201:Activin Receptors, Type I; D028341:Activins; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007265:Inhibins / Q000502:physiology*; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; D007328:Insulin; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; C491708:Pax4 protein, rat; D020033:Protein Isoforms; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D028341:Activins; D007265:Inhibins; D030201:Activin Receptors, Type I