The role of PECAM-1 in vascular cell biology.
Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1) is a 130-kDa integral membrane glycoprotein found on the surface of human platelets and leukocytes, and at the intercellular junctions of endothelial cells. PECAM-1 is a member of the immunoglobulin (Ig) gene superfamily, with six Ig-like loops in the extracytoplasmic domain, a 19-residue transmembrane domain, and a 118-amino acid cytoplasmic tail that contains potential sites for phosphorylation and lipid modification that could potentially modulate its adhesive properties and/or subcellular distribution. Antibodies to PECAM-1 interfere with the ability of endothelial cells to form normal cellular junctions, suggesting that PECAM-1 functions in forming or stabilizing the vascular bed. Anti-PECAM-1 antibodies also have been reported to block neutrophil and monocyte chemotaxis in response to lipopolysaccaride, suggesting that PECAM-1 may play a role in leukocyte motility. PECAM-1-transfected murine L cells, but not untransfected L cells, aggregate in a calcium- and PECAM-1-dependent manner, demonstrating directly that PECAM-1 functions as a cell-cell adhesion molecule. PECAM-1 becomes highly phosphorylated in response to cellular activation and, coincident with phosphorylation, associates with the cytoskeleton of activated, but not resting platelets. The engagement of PECAM-1 with the platelet cytoskeleton enables it to move large distances within the plane of the membrane and may similarly account for the ability of PECAM-1 to localize to the intercellular borders of endothelial cells once cell-cell contact has been achieved. Finally, engagement of PECAM-1 causes up-regulation of integrin function on leukocytes, implicating PECAM-1 as a trigger molecule that may regulate leukocyte trafficking through the vessel wall.
Newman
P J
PJ
Platelet Molecular Biology Laboratory, Blood Research Institute, Milwaukee, Wisconsin 53233.
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007739:L Cells; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011487:Protein Conformation; D014162:Transfection
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D002118:Calcium