Proglucagon is processed to glucagon by prohormone convertase PC2 in alpha TC1-6 cells.
Proglucagon is processed differentially in the pancreatic alpha cells and the intestinal L cells to yield either glucagon or glucagon-like peptide 1, respectively, structurally related hormones with opposing metabolic actions. Here, we have studied the processing of proglucagon in alpha TC1-6 cells, an islet-cell line transformed by simian virus 40 large tumor (T) antigen, a model of the pancreatic alpha cell. We found that these cells process proglucagon at certain dibasic cleavage sites to release glucagon and only small amounts of glucagon-like peptide 1, as demonstrated by both continuous and pulse-chase labeling experiments. Both normal islet alpha cells and alpha TC1-6 cells were shown to express the prohormone convertase PC2 at high levels, but not the related protease PC3. Expression of PC2 antisense RNA in alpha TC1-6 cells inhibited both PC2 production and proglucagon processing concomitantly. We conclude that PC2 is the key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype.
Rouillé
Y
Y
Howard Hughes Medical Institute, University of Chicago, IL 60637.
Westermark
G
G
Martin
S K
SK
Steiner
D F
DF
D000818:Animals; D002460:Cell Line; D053771:Glicentin; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D052336:Proglucagon; D045706:Proprotein Convertase 2; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D013381:Subtilisins / Q000378:metabolism*
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D013381:Subtilisins; D045706:Proprotein Convertase 2