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

EA Partridge, C Le Roy, GM Di Guglielmo, J Pawling… - Science, 2004 - science.org
EA Partridge, C Le Roy, GM Di Guglielmo, J Pawling, P Cheung, M Granovsky, IR Nabi
Science, 2004science.org
The Golgi enzyme β1, 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–β receptors at the cell surface and
delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma …
The Golgi enzyme β1,6 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–β 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.
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