Guyonnet Dupérat V, Jacquelin B, Boisseau P, Arveiler B, Nurden A T
UMR 5533 CNRS, Hôpital Cardiologique, Pessac, France.
Blood. 1998 Jul 1;92(1):25-31.
The serine protease, thrombin, is both a potent agonist for platelet aggregation and a mitogen inducing the proliferation of other cell types. Many cellular responses to thrombin are mediated by a G-protein-coupled thrombin receptor (protease-activated receptor-1, PAR-1). This represents the prototype of a new family of proteolytically cleaved receptors that includes PAR-2 and the recently identified PAR-3. Like PAR-1, PAR-3 is a potential thrombin receptor. Their similar gene structure, mechanism of activation, and colocalization to 5q13 raises the question of a common evolutionary origin and of their belonging to a clustered gene family. Construction of a physical map of the 5q13 region by pulsed-field gel electrophoresis (PFGE) has allowed us to identify six potential CpG islands and to establish a linkage of the PAR genes. Southern blot analysis showed that they were in a cluster on a 560-kb Asc I fragment, in the order PAR-2, PAR-1, and PAR-3. PAR-1 and PAR-2 genes were contained within the identical 240-kb Not I fragment, thus confirming a tight linkage between them. The localization of other CpG islands suggested that more PAR-family genes may be present.
丝氨酸蛋白酶凝血酶既是血小板聚集的强效激动剂，也是诱导其他细胞类型增殖的促有丝分裂原。许多细胞对凝血酶的反应是由G蛋白偶联的凝血酶受体（蛋白酶激活受体-1，PAR-1）介导的。这代表了一个新的蛋白水解切割受体家族的原型，该家族包括PAR-2和最近发现的PAR-3。与PAR-1一样，PAR-3是一种潜在的凝血酶受体。它们相似的基因结构、激活机制以及在5q13上的共定位，引发了关于它们共同进化起源以及是否属于一个成簇基因家族的问题。通过脉冲场凝胶电泳（PFGE）构建5q13区域的物理图谱，使我们能够识别六个潜在的CpG岛，并建立PAR基因的连锁关系。Southern印迹分析表明，它们在一个560 kb的Asc I片段上成簇，顺序为PAR-2、PAR-1和PAR-3。PAR-1和PAR-2基因包含在相同的240 kb Not I片段内，从而证实了它们之间的紧密连锁。其他CpG岛的定位表明可能存在更多的PAR家族基因。
