Publication Date:
2004-10-02
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Partridge, Emily A -- Le Roy, Christine -- Di Guglielmo, Gianni M -- Pawling, Judy -- Cheung, Pam -- Granovsky, Maria -- Nabi, Ivan R -- Wrana, Jeffrey L -- Dennis, James W -- New York, N.Y. -- Science. 2004 Oct 1;306(5693):120-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15459394" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Line, Tumor
;
Cell Membrane/metabolism
;
Cell Movement
;
Cell Transformation, Neoplastic
;
*Endocytosis
;
Galectin 3/metabolism
;
Genetic Vectors
;
Glycosylation
;
Golgi Apparatus/enzymology
;
Growth Substances/metabolism/pharmacology
;
Macrophages, Peritoneal/physiology
;
Mammary Neoplasms, Animal/metabolism/pathology
;
Mice
;
Mice, Transgenic
;
N-Acetylglucosaminyltransferases/genetics/*metabolism
;
Neoplasm Metastasis
;
Phagocytosis
;
Polysaccharides/*metabolism
;
Receptor, Epidermal Growth Factor/*metabolism
;
Receptors, Cytokine/*metabolism
;
Receptors, Transforming Growth Factor beta/*metabolism
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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