Regulation of Cytokine Receptors by Golgi N-Glycan Processing and Endocytosis
Abstract
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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Certain branched glycans can affect a variety of biological functions.
“Beyond their effects on protein structure per se, certain branched glycans can affect a variety of biological functions.”
From Biological roles of glycans (2017) · cites this paper as [605]
There are reports of regulation of cytokine receptors by modulation of endocytosis rates by the type of glycan structure and branching.
“Thus, there are reports of regulation of cytokine receptors by modulation of endocytosis rates by the type of glycan structure and branching (605)”
From Biological roles of glycans (2017) · cites this paper as [605]
Cites
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“Thus, there are reports of regulation of cytokine receptors by modulation of endocytosis rates by the type of glycan structure and branching (605), and N-glycan number and degree of branching can cooperate to regulate cell proliferation and differentiation (606) as 10 A Varki”
BackgroundSignaling Receptors for TGF-β Family Members
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“This also refers to the regulation of cytokine receptors and modulation of endocytosis rates, resulting in the control of cell proliferation and differentiation, as well as clearance from the circulation [48].”
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- Authors
- Partridge, E. A., Le Roy, C., Di Guglielmo, G. M., Pawling, J., Cheung, P., Granovsky, M., Nabi, I. R., Wrana, J. L., & Dennis, J. W.
- Affiliations
- Mount Sinai Hospital (CA)
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.
- Corresponding author
- Dennis, James W.
- Venue
- Science
- Published
- 2004-10
- Volume
- 306
- Issue
- 5693
- Pages
- 120-124
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2066545420
- Cited by
- 735
- References
- 4
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 22 · 2023: 42 · 2022: 21 · 2021: 41 · 2020: 31 · 2019: 24 · 2018: 39 · 2017: 25 · 2016: 41 · 2015: 52 · 2014: 50 · 2013: 26 · 2012: 51
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Immunology and Microbiology › Immunology › Galectins and Cancer Biology
- Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
- Keywords
- MGAT5, N-glycan processing, galectin-3, poly-N-acetyllactosamine, cytokine receptors, epidermal growth factor receptor, TGF-beta receptor, receptor internalization, cytokine signaling, breast cancer, epithelial-mesenchymal transition, metastasis, leukocyte signaling, phagocytosis, leukocyte transmigration
- MeSH terms
- Animals, Cell Membrane, Cell Movement, Cell Transformation, Neoplastic, Endocytosis, Genetic Vectors, Glycosylation, Golgi Apparatus, Growth Substances, Mice, Transgenic, Neoplasm Metastasis, Phagocytosis, Polysaccharides, Signal Transduction, Mammary Neoplasms, Animal, N-Acetylglucosaminyltransferases, Macrophages, Peritoneal, Receptors, Cytokine, Receptors, Transforming Growth Factor beta, Galectin 3, Cell Line, Tumor, Mice, ErbB Receptors
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