Platelet-endothelial cell adhesion molecule (PECAM)-1 first appeared in the literature in 1985, in reports by two different groups. These reports described a 145-kDa glycoprotein of unknown function that was constitutively expressed on the surface of platelets and endothelial cells (ECs) (1); and the 120-kDa target antigen of two murine monoclonal antibodies (mAbs), termed TM2 and TM3, that were derived by immunizing mice with the monocytic leukemia cell line, THP-1 (2). The TM-2/TM-3 antigen was found on all normal peripheral blood monocytes, neutrophils, granulocytes, platelets, and mitogen-activated lymphoblasts, as well as on blasts from various leukemia patients, especially those with leukemia of myeloid origin. Clustering by the 1989 CD Workshop of seven different CD31 mAbs having similar reactivity (3), together with cloning of its cDNA by three different laboratories in 1990 (4–6), permitted a unification of these previously disparate observations. Thereafter, PECAM-1 was assigned to the cell adhesion molecule (CAM) subfamily of immunoglobulin (Ig) gene superfamily receptors.

Human PECAM-1(Figure 115.1) is encoded by an approximately 70-kb gene (7) located at q23 of chromosome 17 (8). The gene is comprised of 16 exons, with exons 2 through 8 encoding the six extracellular Ig-like domains, exon 9 encoding the transmembrane domain, and exons 10 to 16 encoding a complex cytoplasmic domain that is subject to a rather large degree of alternative splicing (9). The cytoplasmic domain contains at least five serine and tyrosine phosphorylation sites, the most well-characterized of which are two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIMs) centered on tyrosine residues 663 and 686 (10). These ITIMs, following phosphorylation during a variety of cellular activation events, serve to recruit cytosolic signaling molecules, in particular the protein tyrosine phosphatase, SHP-2 (11,12).