Switched at birth: a new family for PECAM-1

Platelet endothelial cell adhesion molecule-1 (PECAM-1, or CD31) is a 130-kDa member of the immunoglobulin (Ig) superfamily that is expressed on the surface of circulating platelets, monocytes, neutrophils, and particular T-cell subsets. It is also a major constituent of the endothelial cell intercellular junction, where up to an estimated one million molecules are concentrated. Because of this cellular expression pattern, PECAM-1 is implicated in several functions, including transendothelial migration of leukocytes, angiogenesis, and integrin activation (for a review of the biology of PECAM-1, see ref. 1). When the cDNA sequence for PECAM-1 was determined more than eight years ago (2), it was originally assigned to the growing family of Ig-like cell adhesion molecules (Ig-CAMs). This classification was the result of the sequence similarity of PECAM-1's extracellular Ig domains to those of other Ig-CAMs characterized at that time, including carcinoembryonic antigen (CEA), intercellular adhesion molecule-1 (ICAM-1), and neural cell adhesion molecule (NCAM). Recent observations however, suggest that we may have been following the wrong half of the molecule and that PECAM-1 may not be a member of the Ig-CAM family after all.