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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jackson, D. E. Search for Related Content PubMed Articles by Jackson, D. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2003, Vol. 102, No. 1, pp. 3-4 PECAM-1/CD31 provides survival signals to suppress apoptosis In this issue, Gao and colleagues (page 169) report their interesting findings that the absence of platelet endothelial cell adhesion molecule 1 (PECAM-1) leads to enhanced susceptibility of murine endothelial cells and human T lymphocytes to apoptosis following x-ray irradiation or staurosporine treatment. Specifically, the cytoprotective effects of PECAM-1 were shown to suppress the intrinsic mitochondrial-dependent Bax-induced cytochrome c release, caspase activation, and nuclear fragmentation. The ability of PECAM-1 to deliver survival signals to suppress Bax-induced apoptosis required the outside-in signaling properties of PECAM-1, including homophilic contact binding, intact immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and, in part, recruitment and activation of the protein-tyrosine phosphatase, SHP-2. The authors propose that the formation of the PECAM-1/SHP-2 signaling complex may affect signal transduction pathways that modulate either the location and/or activation state of pre-existing pro- and antiapoptotic components of the cell-death pathway. While the concept that homophilic engagement of PECAM-1 can result in the transduction of survival signals in vascular endothelial cells and in macrophage phagocytosis has been previously demonstrated (Noble et al, J Immunol. 1999;162:1376-1383; Brown et al, Nature. 2002;418:200-203), these workers attempt to define the complex molecular mechanisms by which PECAM-1 may exert cytoprotective effects in suppression of apoptosis. They show that PECAM-1 can negatively regulate intrinsic mitochondrial-dependent Bax-mediated apoptosis by preventing a post–Bax-translocation event, but not extrinsic Fas-mediated apoptosis. This cytoprotective effect of the PECAM-1/SHP-2 signaling pathway does not appear to involve phosphatidylinositol-3 (PI-3) kinase–serine/threonine kinase (Akt), or integrin activation. Further studies will be required to unravel the importance of PECAM-1 ITIM (inhibitory) and ITSM (switch)–signaling properties, the spatial-temporal organization of signaling complexes, and subcellular compartmentalization that lead to modulation of pre-existing signaling circuits, including the cell-death machinery. Denise E. Jackson Austin Research Institute CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis Cunji Gao, Weiyong Sun, Melpo Christofidou-Solomidou, Motoshi Sawada, Debra K. Newman, Carmen Bergom, Steven M. Albelda, Shigemi Matsuyama, and Peter J. Newman Blood 2003 102: 169-179. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jackson, D. E. Search for Related Content PubMed Articles by Jackson, D. E. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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