CHYMOTRYPSIN C CO-ACTIVATION OF HUMAN PANCREATIC PROCARBOXYPEPTIDASES A1 AND A2

胰凝乳蛋白酶 C 协同激活人胰腺羧肽酶 A1 和 A2

• 批准号: 8365590
• 负责人: Miklos Sahin-Toth
• 金额: $ 0.31万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365590
• 关键词: Amino Acids; Biology; C-terminal; Carboxypeptidase; Elastases; Enzyme Precursors; Funding; Grant; Human; Mass Spectrum Analysis; Medicine; National Center for Research Resources; Pancreas; Peptide Hydrolases; Physiological; Principal Investigator; Research; Research Infrastructure; Resources; Source; Trypsin; United States National Institutes of Health; base; chymotrypsin; chymotrypsin C; chymotrypsin-like enzyme; cost

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Human digestive carboxypeptidases CPA1, CPA2 and CPB1 are secreted by the pancreas as inactive proenzymes containing a 94-96 amino-acid long propeptide. Activation of procarboxypeptidases is initiated by proteolytic cleavage at the C-terminal end of the propeptide by trypsin. In this study, we have demonstrated that subsequent cleavage of the propeptide by chymotrypsin C (CTRC) induces a nearly 10-fold increase in the activity of trypsin-activated CPA1 and CPA2, whereas CPB1 activity is unaffected. Other human pancreatic proteases such as chymotrypsin B1, chymotrypsin B2, chymotrypsin-like enzyme-1, elastase 2A, elastase 3A or elastase 3B were found to be inactive or markedly less effective at promoting procarboxypeptidase activation. On the basis of these observations we propose that CTRC is a physiological co-activator of proCPA1 and proCPA2. Furthermore, the results confirm and extend the notion that CTRC is a key regulator of digestive zymogen activation.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 人消化羧肽酶CPA 1、CPA 2和CPB 1由胰腺分泌，作为含有94-96个氨基酸长的前肽的无活性酶原。 羧肽酶原的活化是通过胰蛋白酶在前肽的C-末端的蛋白水解裂解而启动的。 在这项研究中，我们已经证明，胰凝乳蛋白酶C（CTRC）的前肽的后续切割诱导胰蛋白酶激活的CPA 1和CPA 2的活性增加近10倍，而CPB 1活性不受影响。 发现其他人胰腺蛋白酶如胰凝乳蛋白酶B1、胰凝乳蛋白酶B2、胰凝乳蛋白酶样酶-1、弹性蛋白酶2A、弹性蛋白酶3A或弹性蛋白酶3B在促进羧肽酶原活化方面是无活性的或明显不太有效。 基于这些观察，我们提出CTRC是proCPA 1和proCPA 2的生理共激活剂。 此外，结果证实并扩展了CTRC是消化酶原激活的关键调节剂的概念。