title: Proglucagons in vertebrates: Expression and processing of multiple genes in a bony fish.
abstract: In contrast to mammals, where a single proglucagon (PG) gene encodes three peptides: glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 (GLP-1; GLP-2), many non-mammalian vertebrates carry multiple PG genes. Here, we investigate proglucagon mRNA sequences, their tissue expression and processing in a diploid bony fish. Copper rockfish (Sebastes caurinus) express two independent genes coding for distinct proglucagon sequences (PG I, PG II), with PG II lacking the GLP-2 sequence. These genes are differentially transcribed in the endocrine pancreas, the brain, and the gastrointestinal tract. Alternative splicing identified in rockfish is only one part of this complex regulation of the PG transcripts: the system has the potential to produce two glucagons, four GLP-1s and a single GLP-2, or any combination of these peptides. Mass spectrometric analysis of partially purified PG-derived peptides in endocrine pancreas confirms translation of both PG transcripts and differential processing of the resulting peptides. The complex differential regulation of the two PG genes and their continued presence in this extant teleostean fish strongly suggests unique and, as yet largely unidentified, roles for the peptide products encoded in each gene.
authors.affiliation: Department of Biochemistry and Microbiology, and Department of Biology, University of Victoria, Victoria, BC, Canada. Electronic address: erbusby@uvic.ca.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Busby
authors.affiliation: Department of Biochemistry and Microbiology, and Department of Biology, University of Victoria, Victoria, BC, Canada.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mommsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005399:Fishes / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D009928:Organ Specificity; D052336:Proglucagon / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D012333:RNA, Messenger; D052336:Proglucagon
keywords: Alternative splicing; Differential expression; Endocrine pancreas; Intestine; Proglucagon; Teleost