title: Yapsin 1 immunoreactivity in {alpha}-cells of human pancreatic islets: implications for the processing of human proglucagon by mammalian aspartic proteases.
abstract: Yapsin 1 is an aspartic protease from Saccharomyces cerevisiae and belongs to a class of aspartic proteases that demonstrate specificity for basic amino acids. It is capable of processing prohormone substrates at specific basic residue cleavage sites, similar to that of the prohormone convertases, to generate bioactive peptide hormones. An antibody raised against yapsin 1 was previously shown to immunostain endocrine cells of rat pituitary and brain as well as lysates from bovine pituitary secretory granules demonstrating the existence of yapsin 1-like aspartic proteases in mammalian endocrine tissues, potentially involved in peptide hormone production. Here, we show the specific staining of yapsin 1 immunoreactivity in the α-cells of human pancreatic islets. No staining was observed in the β- or δ-cells, indicating a specificity of the staining for glucagon-producing and not insulin- or somatostatin-producing cells. Purified yapsin 1 was also shown to process proglucagon into glucagon in vitro, demonstrating that the prototypical enzyme of this subclass of enzymes can correctly process proglucagon to glucagon. These findings suggest the existence of a yapsin 1-like enzyme exclusively in the α-cells of the islets of Langerhans in humans, which may play a role in the production of glucagon in that tissue.
authors.affiliation: Section on Cellular Neurobiology, Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. cawleyn@mail.nih.gov
authors.forename: Niamh X
authors.initials: NX
authors.lastname: Cawley
authors.forename: Guida
authors.initials: G
authors.lastname: Portela-Gomes
authors.forename: Hong
authors.initials: H
authors.lastname: Lou
authors.forename: Y Peng
authors.initials: YP
authors.lastname: Loh
mesh_terms: D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D005934:Glucagon / Q000096:biosynthesis; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D052336:Proglucagon / Q000378:metabolism*
chemical_list: D052336:Proglucagon; D005934:Glucagon; D016282:Aspartic Acid Endopeptidases