Processing of adrenocorticotropin by two proteases in bovine intermediate lobe secretory vesicle membranes. A distinct acidic, tetrabasic residue-specific calcium-activated serine protease and a PC2-like enzyme.

摘要: Adrenocorticotropin (ACTH) is cleaved at the tetrabasic residue site, in pituitary intermediate lobe secretory vesicles, to yield ACTH1-17 and corticotropin-like peptide (CLIP). then converted alpha-melanocyte-stimulating hormone (N-AcACTH1-13NH2) by first removing Lys15-Lys16-Arg17 residues, followed amidation of COOH terminus acetylation NH2 terminus. Bovine vesicle membranes were screened for proteolytic enzyme activity that will cleave residues ACTH. Two activities with pH optima 5.0-6.0 7.5-8.0 detected. The acidic, ACTH-converting ACTH1-39 between Arg17-Arg18 bond CLIP, but did not paired basic pro-opiomelanocortin. This was characterized as a Ca(2+)-activated serine protease unique specificity ACTH1-39. neutral preferentially generated small extent ACTH1-16 from ACTH1-24. Ca(2+)-dependent inhibited or aspartic inhibitors. significantly immunodepleted antiserum raised against bovine PC2/PC3, together studies, suggests PC2-like protease. optimum, distinct subcellular localization acidic indicate function this vivo conversion vesicles which have an internal pH.