Processing of procarboxypeptidase A and other zymogens in murine mast cells.
By cDNA sequence analyses the proteases found within the secretory granules of immune/inflammatory cells appear to be translated initially as zymogens, but by amino-terminal sequencing they are stored within the granules in an active form. We now show that murine mast cell carboxypeptidase A (MC-CPA) is produced in a zymogen form (MC-pro-CPA) that is present at approximately 0.5% of the level of MC-CPA. MC-pro-CPA is an inactive precursor of MC-CPA and is located within the secretory granules of the mast cells. We have identified one mast cell line, KiSV-MC9, that produces MC-pro-CPA yet cannot process it to the active form despite the fact that these cells can process prochymase and protryptase to their active forms, indicating that a separate mechanism exists for activation of the serine proteases. We show that dipeptidylpeptidase-I is involved in the processing of murine mast cell prochymase and procathepsin G, but does not process MC-pro-CPA or protryptase. Thus, mast cell carboxypeptidase, tryptase, and chymase zymogens are each processed to their active forms by different mechanisms.
Dikov
M M
MM
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0111.
Springman
E B
EB
Yeola
S
S
Serafin
W E
WE
D000595:Amino Acid Sequence; D000818:Animals; D002268:Carboxypeptidases / Q000235:genetics / Q000378:metabolism*; D043422:Carboxypeptidases A; D002401:Cathepsin B / Q000378:metabolism; D020789:Cathepsin C; D002478:Cells, Cultured; D053818:Chymases; D003978:Diazomethane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D014162:Transfection; D053802:Tryptases
D004151:Dipeptides; D004792:Enzyme Precursors; D011994:Recombinant Proteins; C509190:Tpsb2 protein, mouse; C089960:glycylphenylalanine diazomethyl ketone; D003978:Diazomethane; D002268:Carboxypeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C; D043422:Carboxypeptidases A; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509229:Cma2 protein, mouse; C509222:Tpsab1 protein, mouse; D053802:Tryptases; C057832:procathepsin B; D002401:Cathepsin B