Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis

Science. 2004 Oct 1;306(5693):120-4. doi: 10.1126/science.1102109.


The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement
  • Cell Transformation, Neoplastic
  • Endocytosis*
  • ErbB Receptors / metabolism*
  • Galectin 3 / metabolism
  • Genetic Vectors
  • Glycosylation
  • Golgi Apparatus / enzymology
  • Growth Substances / metabolism
  • Growth Substances / pharmacology
  • Macrophages, Peritoneal / physiology
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Transgenic
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Neoplasm Metastasis
  • Phagocytosis
  • Polysaccharides / metabolism*
  • Receptors, Cytokine / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction


  • Galectin 3
  • Growth Substances
  • Polysaccharides
  • Receptors, Cytokine
  • Receptors, Transforming Growth Factor beta
  • poly-N-acetyllactosamine
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
  • ErbB Receptors