Biology of Serine Proteases and Serpins

调节蛋白水解被用来驱动许多生物过程，包括细胞周期、细胞死亡和胚胎模式。它还被认为调节复杂的大脑功能，如学习和记忆。不足为奇的是，蛋白水解调控的缺陷会导致癌症和神经退行性疾病等人类疾病。这项资助的总体目标是了解涉及丝氨酸蛋白酶及其抑制剂（称为丝氨酸蛋白酶）协调作用的调节蛋白水解机制。提出了三个具体目的：1)验证丝氨酸蛋白酶是前转化酶抑制剂的假设，前转化酶是激活多种细胞和致病蛋白的丝氨酸蛋白酶，包括激素、生长因子和毒力决定因子。2)鉴定昆虫黑化反应中丝氨酸蛋白酶

Regulated proteolysis is used to drive many biological processes, including the cell cycle, cell death, and embryonic patterning. It is also thought to mediate complex brain functions such as learning and memory. Not surprisingly, then, defects in regulated proteolysis lead to human pathologies such as cancer and neurodegenerative disease. The overall goal of this grant is to understand the mechanisms of regulated proteolysis involving the coordinated action of serine proteases and their inhibitors called serpins. Three specific aims are proposed: 1) To test the hypothesis that a serpin is an inhibitor of proconvertases, serine proteases that activate a wide range of cellular and pathogenic proteins, including hormones, growth factors, and virulence determinants. 2) To identity serine proteases involved in the melanization reaction, an insect analogue of the mammalian blood clotting reaction and a critical determinant of malarial resistance in the mosquito. 3) To perform an RNAi-based screen for serpin function that ultimately will lead to the identification of new biological processes involving serine proteases and serpins. These studies will exploit Drosophila, which utilizes many of the same molecular and cellular mechanisms as mammals, to learn general principles of how regulated proteolysis involving serine proteases and serpins is used for diverse biological purposes.