on April 10, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print April 10, 2003, doi: 10.1161/01.ATV.0000071347.69358.D9
Published online before print April 10, 2003, doi: 10.1161/01.ATV.0000071347.69358.D9
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Submitted on February 25, 2003
Accepted on March 24, 2003
Signal Transduction Pathways Mediated by PECAM-1. New Roles for an Old Molecule in Platelet and Vascular Cell Biology
Peter J. Newman and Debra K. Newman *
From the Blood Research Institute, The Blood Center of Southeastern Wisconsin (P.J.N., D.K.N.), and the Departments of Pharmacology (P.J.N.), Cellular Biology (P.J.N.), and Microbiology (D.K.N.) and Cardiovascular Center (P.J.N.), Medical College of Wisconsin, Milwaukee, Wis.
* To whom correspondence should be addressed. E-mail: pjnewman{at}bcsew.edu.
Abstract--Recent studies of platelet-endothelial cell adhesion molecule-1 (PECAM-1 [CD31])-deficient mice have revealed that this molecule plays an important role in controlling the activation and survival of cells on which it is expressed. In this review, we focus on the complex cytoplasmic domain of PECAM-1 and describe what is presently known about its structure, posttranslational modifications, and binding partners. In addition, we summarize findings that implicate PECAM-1 as an inhibitor of cellular activation via protein tyrosine kinase-dependent signaling pathways, an activator of integrins, and a suppressor of cell death via pathways that depend on damage to the mitochondria. The challenge of future research will be to bridge our understanding of the functional and biochemical properties of PECAM-1 by establishing mechanistic links between signals transduced by the PECAM-1 cytoplasmic domain and discrete cellular responses.
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