title: Processing of secretogranin II by prohormone convertases: importance of PC1 in generation of secretoneurin.
abstract: Secretoneurin is a recently characterized neuropeptide present in the primary amino acid sequence of secretogranin II. We investigated the proteolytic processing of secretogranin II by prohormone convertases in vivo in a cellular system using the vaccinia virus system. Both PC1 and PC2 can cleave the secretogranin II precursor at sites of pairs of basic amino acids to yield intermediate-sized fragments. Other convertases like PACE4, PC5 and furin were not active. For the formation of the free neuropeptide secretoneurin a different pattern was found. Only PC1 but none of the other convertases tested including PC2 were capable of generating secretoneurin. Our results demonstrate that the prohormone convertases PC1 and PC2 are involved in proteolytic processing of secretogranin II. The neuropeptide secretoneurin can only be generated by PC1 suggesting tissue-specific processing of secretogranin II in neurons expressing different subsets of the prohormone convertases.
authors.affiliation: Department of Pharmacology, University of Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Hoflehner
authors.forename: U
authors.initials: U
authors.lastname: Eder
authors.forename: A
authors.initials: A
authors.lastname: Laslop
authors.forename: N G
authors.initials: NG
authors.lastname: Seidah
authors.forename: R
authors.initials: R
authors.lastname: Fischer-Colbrie
authors.forename: H
authors.initials: H
authors.lastname: Winkler
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002417:Cattle; D002864:Chromogranins; D066298:In Vitro Techniques; D051379:Mice; D008970:Molecular Weight; D009479:Neuropeptides / Q000378:metabolism*; D010449:Peptide Mapping; D045664:Proprotein Convertase 1; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D053381:Secretogranin II
chemical_list: D002864:Chromogranins; D009479:Neuropeptides; D011498:Protein Precursors; D011506:Proteins; D053381:Secretogranin II; C081159:secretoneurin; D043484:Proprotein Convertases; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1; D016282:Aspartic Acid Endopeptidases