O-fucose Modifications of Epidermal Growth Factor-Like Repeats and Thrombospondin Type 1 Repeats: Unusual Modifications in Unusual Places

Cell Mol Life Sci. 2003 Feb;60(2):241-50. doi: 10.1007/s000180300019.

Abstract

Recent discoveries revealing that carbohydrate modifications play critical roles in a wide variety of biological processes have brought wide recognition to the field of glycobiology. Growing attention has focused on the function of unusual O-linked carbohydrate modifications such as O-fucose. O-fucose modifications have been described in several different protein contexts, including epidermal growth factor-like repeats and thrombospondin type 1 repeats. The O-fucose modifications on thrombospondin type 1 repeats have only recently been described, but the site of modification occurs in a region proposed to play a role in cell adhesion. O-fucose modifications on epidermal growth factor-like repeats have been described as important players in several signal transduction systems. For instance, Notch, a cell-surface signaling receptor required for many developmental events, bears multiple O-fucose saccharides on the epidermal growth factor-like repeat of its extracellular domain. The O-fucose moieties serve as a substrate for the beta1,3 N-acetylglucosaminyltransferase activity of Fringe, a known modifier of Notch function. The alteration of O-fucose structures by Fringe influences the ability of Notch ligands to activate the receptor and provides a means to regulate Notch signaling. Thus, O-fucose and Fringe provide a clear example of how carbohydrate modifications can have direct functional consequences on the proteins they modify.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / metabolism*
  • Forecasting
  • Fucose / chemistry
  • Fucose / metabolism*
  • Glycosylation
  • Glycosyltransferases / metabolism
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Models, Biological
  • Thrombospondin 1 / chemistry
  • Thrombospondin 1 / metabolism*

Substances

  • Membrane Proteins
  • Thrombospondin 1
  • Fucose
  • Epidermal Growth Factor
  • Glycosyltransferases