权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Analysis of CS5 co-receptor molecule that specifically inhibits chemotaxis of polymorphonuclear leukocytes

特异性抑制多形核白细胞趋化性的CS5共受体分子分析

基本信息

批准号：
12470058
负责人：
YAMAMOTO Tetsuro
金额：
$ 7.62万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470058/
关键词：
ribosomal protein leukocyte chemotaxis C5a receptor apoptosis transglutaminase inflammation antagonist C5a 光アフィニティ標識

项目摘要

The cross-linked dimer of RP S19 attracted monocytes as an agonist of C5a receptor. On the other hand, the same molecule inhibited the chemotaxis of polymorphonuclear leukocytes (PMN) as an antagonist of the C5a receptor. We initially identified the ligand moieties of the RP S19 dimer to the C5a receptor of monocytes. The RP S19 dimer bound to the C5a receptor by a two-step mechanism. The first ligand and second ligand moieties were identified to be-Lys41-His42-Lys43- and -Leu131-Asp132-Arg133-, respectively.Next, we identified a switch moiety on the RPS19 dimer molecule, which converted the agonist function to the antagonist in the C5a receptor-mediated chemotaxis of PMN. The switch moiety was identified to be from Ile134 to Lys144 (IAGQVAAANKK), which was present following to the second ligand moiety.We made a hypothesis that PMN had a molecule near the C5a receptor, which negatively regulated the intracellular signaling raised by the activated C5a receptor. Then we have been trying to identify the co-receptor molecule. We have prepared a subtraction cDNA library between a PMN cDNA pool and a monocyte cDNA pool. We have tried to prepare an analogue peptide with the second ligand moiety and the switch moiety that bore a fluorescence-labeled photosensitive chemical modifier. However, we have not succeeded to identify the co-receptor molecule of the PMN C5a receptor.

RPS19的交联二聚体作为C5a受体的激动剂吸引了单核细胞。另一方面，该分子作为C5a受体的拮抗剂，可抑制多形核白细胞的趋化作用。我们初步鉴定了RPS19二聚体与单核细胞C5a受体的配基部分。RPS19二聚体通过两步机制与C5a受体结合。第一和第二配体部分分别为-Lys41-His42-Lys43-和-Leu131-Asp132-Arg133-。其次，我们在RPS19二聚体分子上发现了一个开关部分，它在C5a受体介导的PMN趋化中将激动剂功能转化为拮抗剂作用。该开关部分是从Ile134到Lys144(IAGQVAAANKK)，位于第二配体部分之后。我们假设PMN在C5a受体附近有一个分子，它负调控激活的C5a受体引发的细胞内信号转导。然后，我们一直在努力识别共同受体分子。我们构建了一个介于PMN文库和单核细胞文库之间的消减文库。我们试图制备一种带有第二配体部分和带有荧光标记的光敏化学修饰剂的开关部分的模拟肽。然而，我们还没有成功地鉴定出PMN C5a受体的联合受体分子。