Commentary 2.p65

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a 130-kDa member of the immunoglobulin superfamily of cell adhesion molecules. It is characterised by the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic domain that led to its recent assignment to the Ig-ITIM family of inhibitory receptors. PECAM-1 is expressed on the surface of circulating platelets, monocytes, neutrophils, particular T-cell subsets and endothelial cell intercellular junctions. PECAM-1 plays an important role in the adhesion of leukocytes by modulating the affinity of integrins and in their transendothelial migration. PECAM-1 is also involved in transmitting signals into the cell following its engagement, leading to negative regulation of platelet-collagen interactions. PECAM-1 has been shown to become phosphorylated at tyrosine residues Y663 and Y686 in response to many stimuli. When phosphorylated, these tyrosine residues support the binding of the Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2), and may lead to alterations in binding characteristics of PECAM-1. In addition to its role in vascular cell adhesion, there is growing evidence that PECAM-1 can transduce signals that suppress programmed cell death which is thought to be via its ability to inhibit cytochrome C release from mitochondria after exposure of cells to a wide range of cytotoxic stimuli.