PROTEOLYTIC PROCESSING OF SURFACTANT HYDROPHOBIC PROTEIN

表面活性剂疏水蛋白的蛋白水解加工

• 批准号: 2218029
• 负责人: Timothy Edward Weaver
• 金额: $ 16.39万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2218029
• 关键词: cell differentiation; chemical binding; chimeric proteins; complementary DNA; electron microscopy; hydropathy; immunoelectrophoresis; laboratory rat; lung alveolus; molecular weight; perinatal; phosphatidylcholines; phospholipids; posttranslational modifications; protein biosynthesis; protein sequence; proteolipids; proteolysis; pulmonary surfactants; receptor mediated endocytosis; respiratory distress syndrome of newborn; respiratory epithelium; restriction mapping; secretion; surface property; tissue /cell culture

The synthesis and secretion of pulmonary surfactant, a complex mixture of lipids and proteins, by the alveolar epithelium is essential for maintaining the structural integrity of the alveolus during respiration; surfactant insufficiency leads to respiratory distress syndrome, a leading cause of morbidity and mortality i neonates. Surfactant- associated Protein B (SP-B), referred to as SPL (Phe) in the previous funding period, is absolutely required for the function of pulmonary surfactant. Human SP-B is synthesized as a preproprotein of 381 amino acids which is processed to the biologically active peptide of 79 residues by proteolytic cleavage of N- and C-terminal peptides from the precursor. Proteolytic processing of the proprotein, therefore, represents a critical steps in the overall regulation of SP-B expression. The current proposal describes studies to: (1) identify the protease(s) and cleavage sites involved in SP-B proprotein processing in vivo, (2) identify peptide domains involved in the transport and sorting of SP-B within the secretory pathway of the Type II cell, (3) define the role of SP-B in directing surfactant phospholipid trafficking in the biosynthetic and endocytic pathways of the Type II cell, and (4) determine the fate and function of the N- and C-terminal peptides following cleavage form the SP-B proprotein. The overall goal of this research is to determine how SP-B processing is integrated with the biosynthesis and metabolism of other components of the pulmonary surfactant system.

肺表面活性剂的合成和分泌，一种复杂的混合物 通过肺泡上皮的脂质和蛋白质的脂质和蛋白质是必不可少的 在呼吸过程中保持肺泡的结构完整性； 表面活性剂功能不全导致呼吸窘迫综合征，一个 发病率和死亡率的主要原因。 表面活性剂 相关蛋白B（SP-B），在上一个中称为SPL（PHE） 资金期是肺功能的绝对必需的 表面活性剂。 人类SP-B合成为381氨基的预蛋白 加工到79的生物活性肽的酸 N-和C末端肽的蛋白水解切割残基 前体。 因此，普洛蛋白的蛋白水解加工 代表SP-B表达总体调节的关键步骤。 当前的建议将研究描述为：（1）确定蛋白酶 和体内SP-B预蛋白加工的裂解位点，（2） 识别参与SP-B运输和分选的肽结构域 在II型细胞的分泌途径中，（3）定义 SP-B指导表面活性剂在生物合成中的磷脂运输 和II型细胞的内吞途径，（4）确定命运 裂解形式后N-和C末端肽的功能 SP-B原则。 这项研究的总体目标是确定 SP-B加工如何与生物合成和代谢集成在一起 肺表面活性剂系统的其他成分。