Proteases and posttranslational processing of prohormones: a review.
Pioneering work on insulin and on lipotropin, published in 1967, led to the formulation of the hypothesis that biologically active peptides such as peptide hormones are derived from larger precursor molecules by enzymatic cleavage at basic amino acid pairs. Since then, an ever-increasing number of hormones and active peptides including neuropeptides have been found to be contained within the sequence of a larger precursor protein and are released by limited proteolytic cleavage. The hypothesis concerning the posttranslational maturation of precursor molecules into smaller active entities is now firmly established in many tissues (e.g., pituitary gland, pancreas) and for all kinds of organisms (e.g. mammals, fish), though the nature of the enzyme(s) responsible for this maturation process still remains unknown. This article presents current knowledge of the intracellular processing of precursor molecules, especially the conversion of prohormone to hormone. The discussion deals principally with the evidences concerning the localization of the maturation process mainly in the secretory granules, the role of basic amino acid pairs at the cleavage site, and the possible involvement of serine and (or) thiol endopeptidases in that process.
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D003594:Cytoplasmic Granules / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006728:Hormones / Q000096:biosynthesis*; D010281:Parathyroid Hormone / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000378:metabolism; D011333:Pro-Opiomelanocortin; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013045:Species Specificity
D006728:Hormones; D010281:Parathyroid Hormone; D010908:Pituitary Hormones, Anterior; D011498:Protein Precursors; C003219:proparathormone; D011333:Pro-Opiomelanocortin; D010447:Peptide Hydrolases