Universität zu Köln

Schjoldager, Katrine T. -B. G., Vester-Christensen, Malene B., Bennett, Eric Paul, Levery, Steven B., Schwientek, Tilo, Yin, Wu, Blixt, Ola ORCID: 0000-0003-4143-6276 and Clausen, Henrik (2010). O-Glycosylation Modulates Proprotein Convertase Activation of Angiopoietin-like Protein 3 POSSIBLE ROLE OF POLYPEPTIDE GalNAc-TRANSFERASE-2 IN REGULATION OF CONCENTRATIONS OF PLASMA LIPIDS. J. Biol. Chem., 285 (47). S. 36293 - 36304. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

The angiopoietin-like protein 3 (ANGPTL3) is an important inhibitor of the endothelial and lipoprotein lipases and a promising drug target. ANGPTL3 undergoes proprotein convertase processing (RAPR(224) down arrow TT) for activation, and the processing site contains two potential GalNAc O-glycosylation sites immediately C-terminal (TT226). We developed an in vivo model system in CHO ldlD cells that was used to show that O-glycosylation in the processing site blocked processing of ANGPTL3. Genome-wide SNP association studies have identified the polypeptide GalNAc-transferase gene, GALNT2, as a candidate gene for low HDL and high triglyceride blood levels. We hypothesized that the GalNAc-T2 transferase performed critical O-glycosylation of proteins involved in lipid metabolism. Screening of a panel of proteins known to affect lipid metabolism for potential sites glycosylated by GalNAc-T2 led to identification of Thr(226) adjacent to the proprotein convertase processing site in ANGPTL3. We demonstrated that GalNAc-T2 glycosylation of Thr(226) in a peptide with the RAPR(224) down arrow TT processing site blocks in vitro furin cleavage. The study demonstrates that ANGPTL3 activation is modulated by O-glycosylation and that this step is probably controlled by GalNAc-T2.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schjoldager, Katrine T. -B. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vester-Christensen, Malene B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bennett, Eric Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Levery, Steven B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwientek, Tilo UNSPECIFIED UNSPECIFIED UNSPECIFIED Yin, Wu UNSPECIFIED UNSPECIFIED UNSPECIFIED Blixt, Ola UNSPECIFIED orcid.org/0000-0003-4143-6276 UNSPECIFIED Clausen, Henrik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-492424
DOI:	10.1074/jbc.M110.156950
Journal or Publication Title:	J. Biol. Chem.
Volume:	285
Number:	47
Page Range:	S. 36293 - 36304
Date:	2010
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FAMILIAL TUMORAL CALCINOSIS; ALPHA-D-GALACTOSAMINE; POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; BRAIN NATRIURETIC PEPTIDE; STRUCTURAL-CHARACTERIZATION; LINKED GLYCOSYLATION; LIPID CONCENTRATIONS; ENDOTHELIAL LIPASE; HDL METABOLISM; CELL-ADHESION Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49242