Dikov M M, Springman E B, Yeola S, Serafin W E
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0111.
J Biol Chem. 1994 Oct 14;269(41):25897-904.
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.
通过cDNA序列分析发现，免疫/炎症细胞分泌颗粒中的蛋白酶最初似乎是以酶原形式翻译的，但通过氨基末端测序发现它们以活性形式储存在颗粒中。我们现在表明，小鼠肥大细胞羧肽酶A（MC-CPA）是以酶原形式（MC-pro-CPA）产生的，其含量约为MC-CPA水平的0.5%。MC-pro-CPA是MC-CPA的无活性前体，位于肥大细胞的分泌颗粒内。我们鉴定出一种肥大细胞系KiSV-MC9，它能产生MC-pro-CPA，但尽管这些细胞能将前糜蛋白酶和前组织蛋白酶G加工成活性形式，却无法将其加工成活性形式，这表明丝氨酸蛋白酶的激活存在一种独立的机制。我们表明二肽基肽酶-I参与了小鼠肥大细胞前糜蛋白酶和组织蛋白酶G的加工，但不参与MC-pro-CPA或前组织蛋白酶的加工。因此，肥大细胞羧肽酶、组织蛋白酶和糜蛋白酶原分别通过不同的机制加工成活性形式。
