title: Preferential apelin-13 production by the proprotein convertase PCSK3 is implicated in obesity.
abstract: The peptide hormone apelin is translated as a 77-residue preproprotein, truncated to the 55-residue proapelin and, subsequently, to 13-36-residue bioactive isoforms named apelin-13 to -36. Proapelin is hypothesized to be cleaved to apelin-36 and then to the shorter isoforms. However, neither the mechanism of proapelin processing nor the endoproteases involved have been determined. We show direct cleavage of proapelin to apelin-13 by proprotein convertase subtilisin/kexin 3 (PCSK3, or furin) in vitro, with no production of longer isoforms. Conversely, neither PCSK1 nor PCSK7 has appreciable proapelin cleavage activity. Furthermore, we show that both proapelin and PCSK3 transcript expression levels are increased in adipose tissue with obesity and during adipogenesis, suggesting that PCSK3 is responsible for proapelin processing in adipose tissue.
authors.affiliation: Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Shin
authors.forename: Aditya
authors.initials: A
authors.lastname: Pandey
authors.forename: Xiang-Qin
authors.initials: XQ
authors.lastname: Liu
authors.forename: Younes
authors.initials: Y
authors.lastname: Anini
authors.forename: Jan K
authors.initials: JK
authors.lastname: Rainey
keywords: (q)PCR, (quantitative) polymerase chain reaction; Adipocyte differentiation; Furin; MALDI-MS, matrix assisted laser desorption ionization mass spectrometry; PCSK, proprotein convertase subtilisin/kexin; Proapelin; Prohormone processing; Proprotein convertase/subtisilin kexin 3; RP-HPLC, reverse phase high performance liquid chromatography; RT-PCR, reverse transcription-PCR; TEV, tobacco etch virus