Regulation of annexin I by proteolysis in rat alveolar epithelial type II cells.

Limited proteolysis of annexin I occurs endogenously in intact rat lung alveolar epithelial type II cells as revealed by immunoblot analysis. Proteolysis increases in the presence of phorbol 12-myristate 13-acetate (PMA), terbutaline, or ATP, agents that enhance secretion of lung surfactant from type II cells. Calpain, a calcium-dependent neutral protease, was activated in stimulated type II cells and cleaved purified annexin I at the N-terminus minus 26 amino acids. Liposome aggregation activity of truncated annexin I showed ten-fold increase in calcium sensitivity compared to the native form. The results suggest that proteolytic modification may be a regulatory mechanism for annexin I to mediate the secretory processes of alveolar type II cells at physiological calcium concentrations.