Ueda Y
Molecular Medicine Laboratories, Yamanouchi Pharmaceutical Co, Ltd, Ibaraki, Japan.
FEBS Lett. 2000 Sep 1;480(2-3):101-5. doi: 10.1016/s0014-5793(00)01914-1.
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.
激活素A是转化生长因子β超家族的成员之一，具有多种生理和发育功能。在胰腺β细胞培养中，激活素促进细胞分化和胰岛素分泌。作者发现激活素可增加PAX4的基因表达，PAX4是决定胰腺β细胞分化的主要转录因子之一。这种效应至少部分是由I型B激活素受体（ALK4）介导的。此外，人胰岛素启动子-报告系统的活性以独特的方式受PAX4及其异构体PAX4 delta(G239-P251)的调控；低浓度时起正向作用，高浓度时起负向作用。并且这些蛋白质之间的抑制活性有所不同。这些发现证实了激活素信号转导在胰腺β细胞发育和功能中的重要性。
