Watanabe Rie, Shen Zhen-Ping, Tsuda Kinsuke, Yamada Yuichiro
Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 2008 Dec 19;377(3):867-72. doi: 10.1016/j.bbrc.2008.10.074. Epub 2008 Oct 23.
Activins regulate pancreatic development, differentiation and insulin secretion. Activin receptor-like kinase 7 (ALK7) has been identified as a receptor for Nodal and Activin AB and B, and is expressed in pancreatic islets and beta-cell lines. In this study, human insulin promoter was activated by Smad2, Smad3 and the pancreatic and duodenal homeobox factor-1 (PDX-1) in the ALK7 pathway. A conserved Smad binding element was related to the promoter activation. Phosphorylated Smad2/Smad3 and PDX-1 were bound to insulin gene with Nodal and Activin AB, and the phosphorylated Smad2/Smad3 interacted with PDX-1. These results indicate that one of the direct target genes of Nodal and Activin AB signals is the insulin gene in pancreatic beta-cells and that PDX-1 is directly involved in the ALK7-Smad pathway.
激活素调节胰腺发育、分化及胰岛素分泌。激活素受体样激酶7（ALK7）已被确定为Nodal及激活素AB和B的受体，且在胰岛和β细胞系中表达。在本研究中，人胰岛素启动子在ALK7信号通路中被Smad2、Smad3及胰腺和十二指肠同源盒因子-1（PDX-1）激活。一个保守的Smad结合元件与启动子激活相关。磷酸化的Smad2/Smad3和PDX-1与胰岛素基因结合，同时结合Nodal和激活素AB，且磷酸化的Smad2/Smad3与PDX-1相互作用。这些结果表明，Nodal和激活素AB信号的直接靶基因之一是胰腺β细胞中的胰岛素基因，且PDX-1直接参与ALK7-Smad信号通路。
