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

gamma -Carboxylated proteins were detected in normal human pancreas by immu nohistochemistry with a monoclonal antibody (M3B) specific for gamma -carbo xyglutamyl residues, Staining appeared to be localized to the glucagon-secr eting alpha -cells in the islets of Langerhans, Consistent with this, secti ons from a glucagonoma were stained much more intensely with the M3B antibo dy than those from an insulinoma. A murine alpha -cell line (alpha TC1 Clon e 9) was cultured and gamma -carboxylated polypeptides, identified immunolo gically as prothrombin, protein S and (tentatively) Gas6, were isolated fro m the intracellular compartment by chromatography on an M3B-coupled resin, As in liver, prothrombin is synthesized by alpha -cells as a gamma -carboxy lated zymogen that can be cleaved by ecarin to form an active serine protea se that is inhibited by hirudin, The pancreas thus appears to be a novel si te of synthesis for certain vitamin K-dependent proteins. (C) 2001 Academic Press.