Insulin gene is a target in activin receptor-like kinase 7 signaling pathway in pancreatic beta-cells

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / metabolism*
  • Activins / metabolism
  • Animals
  • Base Sequence
  • Cell Line
  • Dogs
  • Guinea Pigs
  • Homeodomain Proteins / metabolism
  • Humans
  • Insulin / genetics*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nodal Protein / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Promoter Regions, Genetic
  • Rats
  • Sequence Alignment
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Trans-Activators / metabolism
  • Transcriptional Activation*


  • Homeodomain Proteins
  • Insulin
  • NODAL protein, human
  • Nodal Protein
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators
  • activin A
  • activin B
  • pancreatic and duodenal homeobox 1 protein
  • Activins
  • Phosphatidylinositol 3-Kinases
  • ACVR1C protein, human
  • Activin Receptors, Type I