Synthesis of gamma-carboxylated polypeptides by alpha-cells of the pancreatic islets

Biochem Biophys Res Commun. 2001 May 4;283(2):454-9. doi: 10.1006/bbrc.2001.4808.

Abstract

gamma-Carboxylated proteins were detected in normal human pancreas by immunohistochemistry with a monoclonal antibody (M3B) specific for gamma-carboxyglutamyl residues. Staining appeared to be localized to the glucagon-secreting alpha-cells in the islets of Langerhans. Consistent with this, sections from a glucagonoma were stained much more intensely with the M3B antibody than those from an insulinoma. A murine alpha-cell line (alphaTC1 Clone 9) was cultured and gamma-carboxylated polypeptides, identified immunologically as prothrombin, protein S and (tentatively) Gas6, were isolated from the intracellular compartment by chromatography on an M3B-coupled resin. As in liver, prothrombin is synthesized by alpha-cells as a gamma-carboxylated zymogen that can be cleaved by ecarin to form an active serine protease that is inhibited by hirudin. The pancreas thus appears to be a novel site of synthesis for certain vitamin K-dependent proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Carboxyglutamic Acid / immunology
  • 1-Carboxyglutamic Acid / metabolism*
  • Animals
  • Antibodies, Monoclonal
  • Clone Cells
  • Glucagonoma / metabolism
  • Humans
  • Immunohistochemistry
  • Insulinoma / metabolism
  • Islets of Langerhans / metabolism*
  • Mice
  • Pancreatic Neoplasms / metabolism
  • Protein Biosynthesis*
  • Protein S / metabolism
  • Proteins / chemistry*
  • Prothrombin / metabolism
  • Vitamin K / metabolism

Substances

  • Antibodies, Monoclonal
  • Protein S
  • Proteins
  • Vitamin K
  • 1-Carboxyglutamic Acid
  • Prothrombin