Pancreatic elastases

描述（由申请人提供）：本拨款提案的目的是表征胰腺弹性蛋白酶的生理功能，并研究弹性蛋白酶突变体作为人类慢性胰腺炎危险因素的机制。这项拨款申请旨在满足胰腺界对胰腺生理学和疾病中弹性酶功能的理解日益增长的需求。在人类中，有五种胰腺弹性酶基因（ELA1, ELA2A, ELA2B， ELA3A和ELA3B）产生三种功能性弹性酶（ELA2A， ELA3A和ELA3B）。在小鼠中，ELA1、ELA2A和ELA3B似乎有表达。研究的具体目的是为了解决(i)人类和小鼠弹性蛋白酶的底物特异性；（ii）前列腺蛋白酶和其他胰腺蛋白酶之间形成复合物；（iii）慢性胰腺炎患者前列腺蛋白酶突变的功能后果。

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.