Secreted alpha amidating enzymes are generated by specific posttranslational processing of precursors containing transmembrane domains

The biosynthesis and secretion of alpha amidating enzymes from CA-77 cells has been investigated to determine the relationship among the various forms of alpha amidating enzyme seen after purification of alpha amidating enzyme activity from conditioned cell culture media. Initially 2 proteins of 104kD and 94kD are synthesized. With time the 104kD precursor is processed to 41kD and 43kD, and the 94kD precursor is processed to 75kD. The 41kD, 43kD, and 75kD proteins are secreted into the medium as functional enzymes. In comparing these data with known cDNA sequence for alpha amidating enzyme we conclude that the 104kD and 94kD precursors are membrane bound proteins which are posttranslationally processed to generate secreted alpha amidating enzyme.