Title : 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
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)↓TT) for activation, and the processing site contains two potential GalNAc O-glycosylation sites immediately C-terminal (TT(226))
- 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)↓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
Output (sent_index, trigger,
protein,
sugar,
site):
- 2. contains, , -, two potential GalNAc O-glycosylation sites immediately C-terminal (TT(226)), site
- 3. O-glycosylation, , -, -, site
- 5. O-glycosylation, , proteins, -, -
- 6. Thr, , -, -, site
- 6. glycosylated, , -, -, sites
- 7. Thr, , -, GalNAc-T2 glycosylation, Thr(226)
- 7. glycosylation, , -, -, Thr(226)
- 7. glycosylation, , -, a peptide, peptide
Output(Part-Of) (sent_index,
protein,
site):
- 6. ANGPTL3, Thr(226)
- 7. -, site
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 7. ANGPTL3, -, Thr(226)
- 7. ANGPTL3, GalNAc-T2 glycosylation, Thr(226)