Synthesis of gamma-carboxylated polypeptides by alpha-cells of the pancreatic islets.
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.
Stenberg
L M
LM
Department of Clinical Chemistry, Department of Pathology, Lund University, University Hospital, Malmö, Sweden.
Nilsson
E
E
Ljungberg
O
O
Stenflo
J
J
Brown
M A
MA
D015055:1-Carboxyglutamic Acid / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D002999:Clone Cells; D005935:Glucagonoma / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism; D014176:Protein Biosynthesis; D017293:Protein S / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*; D011516:Prothrombin / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017293:Protein S; D011506:Proteins; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; D011516:Prothrombin