Quail Sulf1 function requires asparagine-linked glycosylation

J Biol Chem. 2007 Nov 23;282(47):34492-9. doi: 10.1074/jbc.M706744200. Epub 2007 Sep 12.

Abstract

The heparan sulfate endosulfatases Sulf1 and Sulf2 are cell-surface enzymes that control growth factor signaling through regulation of the 6-O-sulfation states of cell-surface and matrix heparan sulfate proteoglycans. Here, we report that quail Sulf1 (QSulf1) is an asparagine-linked glycosylated protein. Domain mapping studies in combination with a protein glycosylation prediction program identified multiple asparagine-linked glycosylation sites in the enzymatic and C-terminal domains. Glycosylation inhibitor studies revealed that glycosylation of QSulf1 is essential for its enzymatic activity, membrane targeting, and secretion. Furthermore, N-glycanase cleavage of asparagine-linked sites in native QSulf1 provided direct evidence that these N-linked glycosylation sites are specifically required for QSulf1 heparin binding and its 6-O-desulfation activity, revealing that N-linked glycosylation has a key role in the control of sulfatase enzymatic function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / metabolism
  • Cell Line
  • Cell Membrane / enzymology*
  • Gene Expression
  • Glycosylation
  • Heparin / metabolism
  • Heparitin Sulfate / metabolism*
  • Humans
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / pharmacology
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology*
  • Protein Structure, Tertiary / physiology
  • Quail / genetics
  • Quail / metabolism*
  • Recombinant Proteins
  • Signal Transduction / physiology*
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism*

Substances

  • Recombinant Proteins
  • Asparagine
  • Heparin
  • Heparitin Sulfate
  • Sulfotransferases
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase