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Xa因子受体EPR-1

Xa receptor EPR-1.

作者信息

Altieri D C

机构信息

Boyer Center for Molecular Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06536, USA.

出版信息

FASEB J. 1995 Jul;9(10):860-5. doi: 10.1096/fasebj.9.10.7615156.

Abstract

Cellular inflammatory responses and early mechanisms of vascular injury are invariably associated with activation of blood coagulation and deposition of insoluble fibrin. This process occurs on vascular cell surfaces through the ability of the coagulation protease factor Xa to generate thrombin. However, experimental evidence accumulated during the past decade underscores how prothrombin activation is only one of the biological consequences of factor Xa assembly on vascular cells. Instead, binding of factor Xa to leukocytes, endothelium, and smooth muscle cells triggers complex pathways of intracellular signal transduction that participate, directly or indirectly, in the regulation of cellular growth. One of the cellular binding sites for factor Xa, designated effector cell protease receptor-1 (EPR-1), has recently emerged as a novel potential regulator of factor Xa-mediated mitogenic signaling. For its activation-dependent phenotype on leukocyte subsets, its ability to costimulate lymphocyte proliferation through release of intracellular second messengers, and its regulated cellular expression by alternative mRNA splicing, EPR-1 may influence vascular cell growth and aberrantly contribute to the earliest pathogenetic processes of vascular diseases.

摘要

细胞炎症反应和血管损伤的早期机制总是与血液凝固的激活和不溶性纤维蛋白的沉积相关。这个过程通过凝血蛋白酶因子Xa在血管细胞表面生成凝血酶的能力而发生。然而,过去十年积累的实验证据强调了凝血酶原激活只是因子Xa在血管细胞上组装的生物学后果之一。相反,因子Xa与白细胞、内皮细胞和平滑肌细胞的结合触发了细胞内信号转导的复杂途径,这些途径直接或间接地参与细胞生长的调节。因子Xa的细胞结合位点之一,称为效应细胞蛋白酶受体-1(EPR-1),最近已成为因子Xa介导的促有丝分裂信号的新型潜在调节剂。由于其在白细胞亚群上的激活依赖性表型、通过释放细胞内第二信使共刺激淋巴细胞增殖的能力以及通过可变mRNA剪接调节细胞表达,EPR-1可能影响血管细胞生长,并异常地促成血管疾病的最早发病过程。

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