Identification of the physiological substrates of PDIp, a pancreas-specific protein-disulfide isomerase family member

Takushi Fujimoto, Orie Nakamura, Michiko Saito, Akio Tsuru, Masaki Matsumoto, Kenji Kohno, Kenji Inaba, Hiroshi Kadokura

研究成果: Article査読

11 被引用数 (Scopus)


About 20 members of the protein-disulfide isomerase (PDI) family are present in the endoplasmic reticulum of mammalian cells. They are thought to catalyze thiol–disulfide exchange reactions within secretory or membrane proteins to assist in their folding or to regulate their functions. PDIp is a PDI family member highly expressed in the pancreas and known to bind estrogen in vivo and in vitro. However, the physiological functions of PDIp remained unclear. In this study, we set out to identify its physiological substrates. By combining acid quenching and thiol alkylation, we stabilized and purified the complexes formed between endogenous PDIp and its target proteins from the mouse pancreas. MS analysis of these complexes helped identify the disulfide-linked PDIp targets in vivo, revealing that PDIp interacts directly with a number of pancreatic digestive enzymes. Interestingly, when pancreatic elastase, one of the identified proteins, was expressed alone in cultured cells, its proenzyme formed disulfide-linked aggregates within cells. However, when pancreatic elastase was co-expressed with PDIp, the latter prevented the formation of these aggregates and enhanced the production and secretion of proelastase in a form that could be converted to an active enzyme upon trypsin treatment. These findings indicate that the main targets of PDIp are digestive enzymes and that PDIp plays an important role in the biosynthesis of a digestive enzyme by assisting with the proper folding of the proenzyme within cells.

ジャーナルJournal of Biological Chemistry
出版ステータスPublished - 2018 11月 30

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学


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