Pancreatic elastases

描述(由申请人提供)：本资助提案的目的是描述胰腺弹性蛋白酶的生理功能，并研究弹性蛋白酶突变作为人类慢性胰腺炎危险因素的机制。这项赠款申请旨在满足胰腺社区对了解弹性蛋白酶在胰腺生理和疾病中的作用的日益增长的需求。在人类中，有五个胰腺弹性蛋白酶基因(ELA1、ELA2A、ELA2B、ELA3A和ELA3B)导致三种功能性弹性酶(ELA2A、ELA3A和ELA3B)。在小鼠中，似乎表达了ELA1、ELA2A和ELA3B。研究的特定目标旨在解决(I)人和小鼠弹性蛋白酶的底物专一性；(Ii)原弹性酶与其他胰腺蛋白酶之间的复合体形成；以及(Iii)在慢性胰腺炎受试者中发现的原弹性酶突变的功能后果。

DESCRIPTION (provided by applicant): The objectives of the present grant proposal are to characterize the physiological functions of pancreatic elastases and to investigate the mechanism by which elastase mutants act as risk factors for chronic pancreatitis in humans. This grant application is intended to meet a growing need in the pancreas community for the understanding of elastase function both in pancreatic physiology and disease. In humans, there are five pancreatic elastase genes (ELA1, ELA2A, ELA2B, ELA3A, and ELA3B) which give rise to three functional elastases (ELA2A, ELA3A and ELA3B). In the mouse ELA1, ELA2A and ELA3B seem to be expressed. The specific aims studied are designed to address (i) the substrate specificity of human and mouse elastases; (ii) complex formation between proelastases and other pancreatic proteases; and (iii) the functional consequences of proelastase mutations identified in subjects with chronic pancreatitis.