Novel targets for antithrombotic drug discovery.
Platelet aggregation is a dynamic entity, capable of directing its own growth and stability via the activation of signaling cascades that lead to the expression and secretion of various secondary agonists. Recent data using proteomics and genomics strategies have established that signaling pathways during platelet aggregation are triggered by two homophilic adhesion molecules, CD84 and CD150 (SLAM), and by a novel EGF-containing receptor, PEAR1, which are tyrosine-phosphorylated in a platelet-aggregation-dependent fashion (N. Nanda, P. Andre, M. Bao et al., Platelet aggregation induces platelet aggregate stability via SLAM family receptor signaling, Blood 106 (2005) 3028-3034, N. Nanda, M. Bao, H. Lin et al., Platelet Endothelial Aggregation Receptor 1 (PEAR1), a novel epidermal growth factor repeat-containing transmembrane receptor, participates in platelet contact-induced activation, J. Biol. Chem. 280 (2005) 24680-24689). Analysis of SLAM-deficient mice revealed an overall defect in platelet aggregation in vitro and a delayed arterial thrombotic process in vivo. The data indicate that these aggregation co-receptors may function in a "platelet synapse" and may be novel targets for antithrombotic drug discovery.
Portola Pharmaceuticals Inc., 270 E. Grand Avenue, South San Francisco, CA 94080, USA.
Nisha
N
Nanda
David R
DR
Phillips
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D016503:Drug Delivery Systems; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010974:Platelet Aggregation; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; C498970:CD84 protein, human; D005343:Fibrinolytic Agents; C502809:PEAR1 protein, human; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1