Open AccessPreferential apelin‐13 production by the proprotein convertase PCSK3 is implicated in obesity
Author(s) -
Shin Kyungsoo,
Pandey Aditya,
Liu Xiang-Qin,
Anini Younes,
Rainey Jan K.
Publication year - 2013
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2013.08.001
Subject(s) - proprotein convertase , furin , apelin , prohormone convertase , kexin , gene isoform , adipose tissue , chemistry , endocrinology , medicine , proprotein convertases , subtilisin , biochemistry , biology , hormone , prohormone , enzyme , gene , receptor , lipoprotein , cholesterol , ldl receptor
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.