Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity

Xia Lei, Fujun Shi, Debapriya Basu, Afroza Huq, Sophie Routhier, Robert Day, Weijun Jin

Research output: Contribution to journalArticle

Abstract

Angiopoietin-like protein 4 (ANGPTL4) has been associated with a variety of diseases. It is known as an endogenous inhibitor of lipoprotein lipase (LPL), and it modulates lipid deposition and energy homeostasis. ANGPTL4 is cleaved by unidentified protease(s), and the biological importance of this cleavage event is not fully understood with respect to its inhibitory effect on LPL activity. Here, we show that ANGPTL4 appears on the cell surface as the full-length form, where it can be released by heparin treatment in culture and in vivo. ANGPTL4 protein is then proteolytically cleaved into several forms by proprotein convertases (PCs). Several PCs, including furin, PC5/6, paired basic amino acid-cleaving enzyme 4, and PC7, are able to cleave human ANGPTL4 at a consensus site. PC-specific inhibitors block the processing of ANGPTL4. Blockage of ANGPTL4 cleavage reduces its inhibitory effects on LPL activity and decreases its ability to raise plasma triglyceride levels. In summary, the cleavage of ANGPTL4 by these PCs modulates its inhibitory effect on LPL activity.

Original languageEnglish (US)
Pages (from-to)15747-15756
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number18
DOIs
StatePublished - May 6 2011
Externally publishedYes

Fingerprint

Angiopoietins
Proprotein Convertases
Lipoprotein Lipase
Processing
Proteins
Furin
Heparin
Triglycerides
Homeostasis
Peptide Hydrolases
Lipids
Plasmas

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity. / Lei, Xia; Shi, Fujun; Basu, Debapriya; Huq, Afroza; Routhier, Sophie; Day, Robert; Jin, Weijun.

In: Journal of Biological Chemistry, Vol. 286, No. 18, 06.05.2011, p. 15747-15756.

Research output: Contribution to journalArticle

Lei, Xia ; Shi, Fujun ; Basu, Debapriya ; Huq, Afroza ; Routhier, Sophie ; Day, Robert ; Jin, Weijun. / Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 18. pp. 15747-15756.
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