title: Enzymatic activity of soluble and membrane tethered peptide pro-hormone convertase 1.
abstract: Pro-hormone convertases PC1 and PC2 perform endoproteolytic cleavages of precursors in peptide-containing secretory granules. PC1 and PC2 are soluble, secreted with bioactive peptides. Evolutionarily related PCs have membrane tethers, not secreted. We tethered PC1 to the transmembrane-cytoplasmic domains (CD) of a granule enzyme (peptidylglycine-alpha-amidating monooxygenase; PAM) and Golgi-localized PC8. The tethered PC1 is far more stable to elevated temperature and denaturants than soluble PC1, and more active. Both tethers allow PC1 to visit the cell surface transiently, cleaving soluble molecules outside the cell. Both membrane-bound PC1 chimeras cleave membrane PAM into soluble active fragments when PAM is expressed on adjacent cells.
authors.affiliation: Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Bruzzaniti
authors.forename: Richard E
authors.initials: RE
authors.lastname: Mains
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002384:Catalysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D004795:Enzyme Stability; D006728:Hormones / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010802:Phylogeny; D043484:Proprotein Convertases; D011817:Rabbits; D051381:Rats; D012995:Solubility; D013379:Substrate Specificity
chemical_list: D004792:Enzyme Precursors; D006728:Hormones; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases