title: Post-translational modifications of heterologously expressed cholecystokinin in Saccharomyces cerevisiae.
abstract: The vertebrate neuroendocrine peptide cholecystokinin (CCK) is subjected to numerous post-translational modifications upon maturation to bioactive CCK. However, the current knowledge of the proteolytic processing of proCCK, as reviewed here, is not complete. We have chosen Saccharomyces cerevisiae as a model to study these endoproteolytic processing events. Expression of proCCK as a fusion protein to the prepro leader peptide of alpha-mating factor directed the protein through the secretory pathway and resulted in nanomolar concentrations of secreted glycine-extended CCK. The CCK peptides showed many correlations to the known endoproteolytic processing products of proCCK in endocrine cells. Especially the processing to the abundant form, CCK-22, was investigated and it is suggested that a novel enzyme is responsible for its production. Thus, yeast may be used to study the proteolysis of proCCK with the aim to identify mammalian homologues involved in maturation of CCK.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark. lajo@biobase.dk
authors.forename: L
authors.initials: L
authors.lastname: Jønson
authors.forename: A H
authors.initials: AH
authors.lastname: Johnsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; C060249:procholecystokinin; C042082:preprocholecystokinin; D002766:Cholecystokinin