Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology.
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.
Newman
Peter J
PJ
Blood Research Institute, The Blood Center of Southeastern Wisconsin, PO Box 2178, 638 N. 18th St, Milwaukee, Wis 53201, USA. pjnewman@bcsew.edu
Newman
Debra K
DK
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D015539:Platelet Activation / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
D016023:Integrins; D019408:Platelet Endothelial Cell Adhesion Molecule-1