Suppression of tumor-related glycosylation of cell surface receptors by the 16-kDa membrane subunit of vacuolar H+-ATPase.
The glycosylation of integrins and other cell surface receptors is altered in many transformed cells. Notably, an increase in the number of beta1,6-branched N-linked oligosaccharides correlates strongly with invasive growth of cells. An ectopic expression of the Golgi enzyme N-acetylglucosaminyltransferase V (GlcNAc-TV), which forms beta1,6 linkages, promotes metastasis of a number of cell types. It is shown here that the 16-kDa transmembrane subunit (16K) of vacuolar H(+)-ATPase suppresses beta1,6 branching of beta(1) integrin and the epidermal growth factor receptor. Overexpression of 16K inhibits cell adhesion and invasion. 16K contains four hydrophobic membrane-spanning alpha-helices, and its ability to influence glycosylation is localized primarily within the second and fourth membrane-spanning alpha-helices. 16K also interacts directly with the transmembrane domain of beta(1) integrin, but its effects on glycosylation were independent of its binding to beta(1) integrin. These data link cell surface tumor-related glycosylation to a component of the enzyme responsible for acidification of the exocytic pathway.
Skinner
M A
MA
Department of Molecular Biology and Genetics, University of Guelph, Guelph, Ontario N1G 2W1, Canada. mskinner@uoguelph.ca
Wildeman
A G
AG
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*
D017931:DNA Primers; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D011956:Receptors, Cell Surface; D066246:ErbB Receptors; D025262:Vacuolar Proton-Translocating ATPases