α2,6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule (PECAM) Regulates Its Homophilic Interactions and Downstream Antiapoptotic Signaling

• Published in: The Journal of biological chemistry Vol. 285; no. 9; p. 6515
• Main Authors: Shinobu Kitazume, Rie Imamaki, Kazuko Ogawa, Yusuke Komi, Satoshi Futakawa, Soichi Kojima, Yasuhiro Hashimoto, Jamey D. Marth, James C. Paulson, Naoyuki Taniguchi
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 26-02-2010
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.073106

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 α2,6-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 α2,6-sialic acid. We
also found that the absence of α2,6-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.