ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes, is up-regulated after vascular injury

ESDN, a novel neuropilin-like membrane protein cloned from vascular cells with the longest secretory signal sequence among eukaryotes, is up-regulated after vascular injury
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DOI:
10.1074/jbc.m105293200
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发表时间:
2001-09-07
影响因子:
4.8
通讯作者:
Tashiro, K
Tashiro, K
中科院分区:
生物学2区
文献类型:
--
作者:
Kobuke, K;Furukawa, Y;Tashiro, K

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用信号序列捕获法从原代培养的人冠状动脉细胞中分离到一个新的cDNA,命名为ESDN((e)条内皮细胞下和(s)条平滑肌细胞下-(d)条内皮细胞下-(n)条Europilin-like分子下)。ESDN是真核生物中具有最长可切割分泌信号序列的I型跨膜蛋白。ESDN含有一个CUB结构域和一个凝血因子V/VIII同源结构域,这使我们想起了神经纤毛蛋白的结构。ESDN还具有LCCL结构域,其由鲎因子C和Coch共享。还鉴定了小鼠和大鼠对应物,揭示了与人ESDN> 84%的氨基酸同一性。人类ESDN基因定位在D3 S1552和D3 S1271之间。北方印迹分析显示ESDNmRNA在多种组织中表达,尤其在培养的血管平滑肌细胞中表达量较高。ESDN的表达上调血小板衍生生长因子-BB刺激的血管平滑肌细胞在体外和球囊损伤的颈动脉在体内的新生内膜。在293 T细胞中过表达ESDN抑制其溴脱氧尿苷摄取。此外,ESDN蛋白在啮齿类动物的神经束中强烈表达。因此,ESDN被认为在调节血管细胞生长中起作用,并且可能在包括神经系统在内的其他组织中具有多种功能,如神经纤毛蛋白。
A novel cDNA has been isolated from primary culture of human coronary arterial cells by a signal sequence trap method, and designated ESDN ((e) under bar ndothelial and (s) under bar mooth muscle cell-(d) under bar erived (n) under bar europilin-like molecule). ESDN is a type-I transmembrane protein with the longest cleavable secretory signal sequence among eukaryotes. ESDN contains a CUB domain and a coagulation factor V/VIII homology domain, which reminds us of the structure of neuropilins. ESDN also harbors an LCCL domain, which is shared by Limulus factor C and Coch. Mouse and rat counterparts were also identified revealing > 84% amino acid identity with human ESDN. The human ESDN gene was mapped between D3S1552 and D3S1271. Northern blot analysis showed that ESDN mRNA was expressed in various tissues; particularly highly expressed in cultured vascular smooth muscle cells. The ESDN expression was up-regulated in platelet-derived growth factor-BB-stimulated vascular smooth muscle cells in vitro and neointima of the balloon-injured carotid artery in vivo. Overexpression of ESDN in 293T cells suppressed their bromodeoxyuridine uptake. In addition, ESDN protein was strongly expressed in nerve bundles in rodents. Thus, ESDN is considered to play a role in regulation of vascular cell growth and may have a wide variety of functions in other tissues including the nervous system, like neuropilins.