Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I / metabolism*
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Activins / metabolism
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Animals
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Base Sequence
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Cell Line
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Dogs
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Guinea Pigs
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Homeodomain Proteins / metabolism
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Humans
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Insulin / genetics*
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Insulin-Secreting Cells / metabolism*
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Mice
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Molecular Sequence Data
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Nodal Protein / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Promoter Regions, Genetic
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Rats
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Sequence Alignment
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Smad2 Protein / metabolism
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Smad3 Protein / metabolism
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Trans-Activators / metabolism
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Transcriptional Activation*
Substances
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Homeodomain Proteins
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Insulin
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NODAL protein, human
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Nodal Protein
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SMAD2 protein, human
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SMAD3 protein, human
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Smad2 Protein
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Smad3 Protein
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Trans-Activators
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activin A
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activin B
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pancreatic and duodenal homeobox 1 protein
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Activins
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Phosphatidylinositol 3-Kinases
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ACVR1C protein, human
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Activin Receptors, Type I