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Type: Journal article
Title: Sphingosine kinase-1 associates with Integrin alpha(V)beta(3) to mediate endothelial cell survival
Author: Gamble, J.
Sun, W.
Li, X.
Hahn, C.
Pitson, S.
Vadas, M.
Bonder, C.
Citation: American Journal of Pathology, 2009; 175(5):2217-2225
Publisher: Amer Soc Investigative Pathology Inc
Issue Date: 2009
ISSN: 0002-9440
Statement of
Jennifer R. Gamble, Wai Y. Sun, Xiaochun Li, Christopher N. Hahn, Stuart M. Pitson, Mathew A. Vadas and Claudine S. Bonder
Abstract: Sphingosine kinase (SK)-1 promotes endothelial cell (EC) survival through the cell junction molecule CD31 (platelet endothelial cell adhesion molecule-1). The integrin vβ3 is also essential for EC survival; inhibition of vβ3 ligation promotes apoptosis. Herein we demonstrate that under basal conditions, SK-1, vβ3, and CD31 exist as a heterotrimeric complex. Under conditions that affect EC survival such as loss of contact with the extracellular matrix or growth factor activation, more of this heterotrimeric complex forms. Overexpression studies demonstrate a requirement for SK-1 phosphorylation at serine 225 for increased heterotrimeric complex formation, activation of vβ3, and EC survival signals, including Bcl-X and nuclear factor-B pathways. Moreover, β3 integrin depletion confirmed the requirement for this heterotrimeric complex in SK-1-mediated EC survival. Thus, with vβ3 integrin being identifiable primarily on angiogenic ECs and SK-1 being highly expressed in tumors, targeting SK-1 may affect multiple survival pathways, and its inhibition may be highly efficacious in controlling pathological EC survival.
Keywords: Cells, Cultured
Focal Adhesions
Endothelial Cells
Phosphotransferases (Alcohol Group Acceptor)
Integrin alphaVbeta3
Membrane Proteins
Proto-Oncogene Proteins
RNA, Small Interfering
Cell Survival
Apoptosis Regulatory Proteins
Focal Adhesion Protein-Tyrosine Kinases
Bcl-2-Like Protein 11
Platelet Endothelial Cell Adhesion Molecule-1
DOI: 10.2353/ajpath.2009.090076
Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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