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单一C基序-1/淋巴细胞趋化因子受体XCR1的鉴定

Identification of single C motif-1/lymphotactin receptor XCR1.

作者信息

Yoshida T, Imai T, Kakizaki M, Nishimura M, Takagi S, Yoshie O

机构信息

Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566-0022, Japan.

出版信息

J Biol Chem. 1998 Jun 26;273(26):16551-4. doi: 10.1074/jbc.273.26.16551.

Abstract

Single C motif-1 (SCM-1)/lymphotactin is a member of the chemokine superfamily, but retains only the 2nd and 4th of the four cysteine residues conserved in other chemokines. In humans, there are two highly homologous SCM-1 genes encoding SCM-1alpha and SCM-1beta with two amino acid substitutions. To identify a specific receptor for SCM-1 proteins, we produced recombinant SCM-1alpha and SCM-1beta by the baculovirus expression system and tested them on murine L1.2 cells stably expressing eight known chemokine receptors and three orphan receptors. Both proteins specifically induced migration in cells expressing an orphan receptor, GPR5. The migration was chemotactic and suppressed by pertussis toxin, indicating coupling to a Galpha type of G protein. Both proteins also induced intracellular calcium mobilization in GPR5-expressing L1.2 cells with efficient mutual cross desensitization. SCM-1alpha bound specifically to GPR5-expressing L1.2 cells with a Kd of 10 nM. By Northern blot analysis, GPR5 mRNA of about 5 kilobases was detected strongly in placenta and weakly in spleen and thymus among various human tissues. Identification of a specific receptor for SCM-1 would facilitate our investigation on its biological function. Following the set rule for the chemokine receptor nomenclature, we propose to designate GPR5 as XCR1 from XC chemokine receptor-1.

摘要

单C基序-1(SCM-1)/淋巴细胞趋化因子是趋化因子超家族的成员,但仅保留了其他趋化因子中保守的四个半胱氨酸残基中的第二个和第四个。在人类中,有两个高度同源的SCM-1基因,它们编码SCM-1α和SCM-1β,两者有两个氨基酸替换。为了鉴定SCM-1蛋白的特异性受体,我们通过杆状病毒表达系统制备了重组SCM-1α和SCM-1β,并在稳定表达八种已知趋化因子受体和三种孤儿受体的小鼠L1.2细胞上对它们进行了测试。两种蛋白都能特异性地诱导表达孤儿受体GPR5的细胞迁移。这种迁移是趋化性的,并被百日咳毒素抑制,表明它与Gα型G蛋白偶联。两种蛋白还能在表达GPR5的L1.2细胞中诱导细胞内钙动员,并具有有效的相互交叉脱敏作用。SCM-1α以10 nM的解离常数特异性结合表达GPR5的L1.2细胞。通过Northern印迹分析,在各种人类组织中,约5千碱基的GPR5 mRNA在胎盘中被强烈检测到,在脾脏和胸腺中则较弱。鉴定SCM-1的特异性受体将有助于我们对其生物学功能的研究。按照趋化因子受体命名的既定规则,我们建议将GPR5命名为XC趋化因子受体-1(XCR1)。

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