The prohormone convertases PC1 and PC2 mediate distinct endoproteolytic cleavages in a strict temporal order during proopiomelanocortin biosynthetic processing

• Published in: The Journal of biological chemistry Vol. 268; no. 3; pp. 1763 - 1769
• Main Authors: Zhou, A, Bloomquist, B T, Mains, R E
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25.01.1993
• Subjects: Adrenocorticotropic Hormone - metabolism; alpha-MSH - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; beta-Endorphin - metabolism; beta-Lipotropin - metabolism; Biological and medical sciences; Brain - enzymology; Cell Line; cleavage; enzymatic activity; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Gene Expression; Hydrolases; Kinetics; Melanocyte-Stimulating Hormones - metabolism; Mice; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - metabolism; Pituitary Gland - enzymology; Pro-Opiomelanocortin - biosynthesis; Pro-Opiomelanocortin - genetics; processing; prohormone convertase PC1; prohormone convertase PC2; proopiomelanocortin; Proprotein Convertase 1; Proprotein Convertase 2; Proprotein Convertases; Rats; RNA, Messenger - metabolism; Serine Endopeptidases - genetics; Serine Endopeptidases - metabolism; synthesis; Transfection; Vertebrata; Mammalia; Molecular processing; Rat; Enzyme; Rodentia; Proopiocortin; Pituitary gland; Biosynthesis; Brain (vertebrata)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)53918-1

Two subtilisin-like endoproteases called PC1 and PC2 are distributed in a tissue-specific manner in the pituitary and in the brain. AtT-20 cells and corticotropes of the anterior pituitary express primarily PC1 and perform a limited number of cleavages of the proopiomelanocortin (POMC) precursor during biosynthesis. Melanotropes of the intermediate pituitary express both PC1 and PC2 and perform a more extensive set of cleavages during the biosynthetic processing of POMC. To investigate the role of PC2 in the biosynthetic processing of POMC, AtT-20 mouse corticotropes were stably transfected with a full length PC2 cDNA. The AtT-20 cells expressing PC2 acquired the ability to perform all the additional cleavages seen in the intermediate pituitary, but did not acquire the ability to alpha-N-acetylate the product peptides. The kinetics of the earliest steps in biosynthetic processing were unaltered by the expression of PC2, and the changes due to PC2 expression were seen only in the middle and late steps in biosynthetic processing. Thus, both the identity of the final product peptides and the kinetics of the processing steps in the AtT-20 cells expressing PC2 fit the patterns expected for melanotropes of the intermediate pituitary.