Nanda Nisha, Phillips David R
Portola Pharmaceuticals Inc., 270 E. Grand Avenue, South San Francisco, CA 94080, USA.
Blood Cells Mol Dis. 2006 Mar-Apr;36(2):228-31. doi: 10.1016/j.bcmd.2005.12.026. Epub 2006 Feb 13.
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.
血小板聚集是一个动态过程，能够通过激活信号级联反应来指导自身的生长和稳定性，这些信号级联反应会导致各种二级激动剂的表达和分泌。最近使用蛋白质组学和基因组学策略的数据表明，血小板聚集过程中的信号通路由两种同源性粘附分子CD84和CD150（信号淋巴细胞激活分子）以及一种含表皮生长因子的新型受体PEAR1触发，它们以血小板聚集依赖性方式发生酪氨酸磷酸化（N. 南达、P. 安德烈、M. 包等人，《血小板聚集通过信号淋巴细胞激活分子家族受体信号传导诱导血小板聚集体稳定性》，《血液》106 (2005) 3028 - 3034，N. 南达、M. 包、H. 林等人，《血小板内皮聚集受体1（PEAR1），一种含新型表皮生长因子重复序列的跨膜受体，参与血小板接触诱导的激活》，《生物化学杂志》280 (2005) 24680 - 24689）。对缺乏信号淋巴细胞激活分子的小鼠的分析揭示了体外血小板聚集的整体缺陷以及体内动脉血栓形成过程的延迟。数据表明，这些聚集共受体可能在“血小板突触”中发挥作用，并且可能是抗血栓药物研发的新靶点。
