Homophilic PECAM-1(CD31) interactions prevent endothelial cell apoptosis but do not support cell spreading or migration.
PECAM-1 (CD31) is a highly abundant cell surface glycoprotein expressed on haemopoietic and endothelial cells. As well as mediating homophilic (PECAM-1/PECAM-1) adhesion, PECAM-1 can also bind the integrin alphavbeta3. Both PECAM-1 and alphavbeta3 have been shown to have roles in regulating angiogenesis, endothelial tube formation and in the case of alphavbeta3, endothelial cell apoptosis. In this study we show that despite being expressed at equivalent levels, endothelial alphavbeta3 is not a ligand for PECAM-1. Rather, PECAM-1 supports homophilic binding on HUVEC with similar characteristics to those we have previously reported for leukocytes and becomes tyrosine phosphorylated after homophilic PECAM-1 and integrin/fibronectin engagement. Immunoprecipitation studies show that in addition to SHP-2, tyrosine phosphorylated PECAM-1 can interact with at least four other phosphoproteins in pervanadate stimulated HUVEC. While PECAM-1/PECAM-1 interactions support robust endothelial cell adhesion, they do not support cell spreading or migration. In addition PECAM-1 homophilic adhesion rescues HUVEC from serum deprivation-induced apoptosis. Taken together our results indicate that PECAM-1 homophilic interactions play an important role in interendothelial cell adhesion, survival and signalling.
Bird
I N
IN
Cell Adhesion Laboratory, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
Taylor
V
V
Newton
J P
JP
Spragg
J H
JH
Simmons
D L
DL
Salmon
M
M
Buckley
C D
CD
D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000378:metabolism
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019030:Receptors, Vitronectin