Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 9, Pages 6515-6521Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.073106
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Funding
- National Institutes of Health [HL57345]
- Systems Glycobiology Research Project
- RIKEN
- Japan Foundation for Applied Enzymology
- Yamada Science Foundation
- Ministry of Education, Science, Sports and Culture of Japan [18570141]
- Grants-in-Aid for Scientific Research [18570141] Funding Source: KAKEN
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Antiangiogenesis therapies are now part of the standard repertoire of cancer therapies, but the mechanisms for the proliferation and survival of endothelial cells are not fully understood. Although endothelial cells are covered with a glycocalyx, little is known about how endothelial glycosylation regulates endothelial functions. Here, we show that alpha 2,6-sialic acid is necessary for the cell-surface residency of platelet endothelial cell adhesion molecule ( PECAM), a member of the immunoglobulin superfamily that plays multiple roles in cell adhesion, mechanical stress sensing, antiapoptosis, and angiogenesis. As a possible underlying mechanism, we found that the homophilic interactions of PECAM in endothelial cells were dependent on alpha 2,6-sialic acid. We also found that the absence of alpha 2,6-sialic acid down-regulated the tyrosine phosphorylation of PECAM and recruitment of Src homology 2 domain-containing protein-tyrosine phosphatase 2 and rendered the cells more prone to mitochondrion-dependent apoptosis, as evaluated using PECAM-deficient endothelial cells. The present findings open up a new possibility that modulation of glycosylation could be one of the promising strategies for regulating angiogenesis.
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