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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 人消化羧肽酶CPA1，CPA2和CPB1被胰腺分泌为含有94-96氨基酸长丙肽的无活性蛋白酶。 procarbasypphidass的激活是通过胰蛋白酶在丙肽的C末端蛋白水解裂解引发的。 在这项研究中，我们已经证明，随后通过胰凝乳蛋白酶C（CTRC）对丙肽的切割诱导胰蛋白酶激活的CPA1和CPA2的活性增加了近10倍，而CPB1活性未受到影响。 发现其他人胰腺蛋白酶，例如胰凝乳蛋白酶B1，胰凝乳蛋白酶B2，甲状腺素蛋白酶样酶-1，弹性酶2a，弹性酶3a或弹性酶3a或弹性酶3B，在促进Procarboxypeptidase激活方面无效或明显较小。 根据这些观察，我们建议CTRC是procpa1和procpa2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观念。