Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets.
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the recruitment of signaling proteins that bind by way of Src-homology domain 2 interactions. Proteins that have been implicated in the negative regulation of cellular activation by ITIM-bearing receptors include the tyrosine phosphatases SHP-1 and SHP-2. Tyrosine phosphorylation of immunoreceptor tyrosine-based activatory motif (ITAM)-bearing receptors such as the collagen receptor GPVI-Fc receptor gamma-chain complex on platelets leads to activation. Increasing evidence suggests that ITIM- and ITAM-containing receptors may act antagonistically when expressed on the same cell. In this study it is demonstrated that cross-linking PECAM-1 inhibits the aggregation and secretion of platelets in response to collagen and the GPVI-selective agonist convulxin. In these experiments thrombin-mediated platelet aggregation and secretion were also reduced, albeit to a lesser degree than for collagen, suggesting that PECAM-1 function may not be restricted to the inhibition of ITAM-containing receptor pathways. PECAM-1 activation also inhibited platelet protein tyrosine phosphorylation stimulated by convulxin and thrombin; this was accompanied by inhibition of the mobilization of calcium from intracellular stores. These data suggest that PECAM-1 may play a role in the regulation of platelet function in vivo.
Cicmil
Milenko
M
School of Animal and Microbial Sciences, University of Reading, United Kingdom.
Thomas
Joanne M
JM
Leduc
Mireille
M
Bon
Cassian
C
Gibbins
Jonathan M
JM
D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D003432:Cross-Linking Reagents; D003435:Crotalid Venoms / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D037181:Lectins, C-Type; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology
D000906:Antibodies; D003432:Cross-Linking Reagents; D003435:Crotalid Venoms; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019000:Phosphotyrosine; C028890:convulxin; D003094:Collagen; D013917:Thrombin; D002118:Calcium