Roles of conserved intracellular sequences regions for the proper expression of dopamine D(2) and D(3) receptors.
Roles of conserved intracellular sequences regions for the proper expression of dopamine D(2) and D(3) receptors.
复制标题
保守的细胞内序列区域对于多巴胺 D(2) 和 D(3) 受体正确表达的作用。
DOI：
10.1007/s12272-001-1205-6
复制
发表时间：
2008
影响因子：
6.7
通讯作者：
Kim,Kyeong-Man
中科院分区：
文献类型：
--
作者：
Cho,Eun-Young;Park,JaeH;Kim,Kyeong-Man
多巴胺D2受体和D3受体（D2 R，D3 R）在氨基酸组成和信号通路上具有高度同源性。事实上，迄今为止报道的所有信号传导途径在两种受体之间重叠，除了D3 R信号的效率比D2 R低2.5倍。以前的研究表明，D3 R的构象限制可能是负责与G蛋白偶联差。针对这一假设，在D2 R和D3 R之间的一些保守区域引入点突变，并研究其对受体表达的影响。在所检测的4个保守的胞内受体区域（第一胞内环的TTT基序、第二胞内环的SS基序、第三胞内环的YxxL和TxxS/xS基序）中，第一胞内环的Thr-Thr-Thr（TTT）基序或第三胞内环的LxxY基序的突变显著降低了D3 R的表达水平。TTT基序进一步单独或组合突变，以测试哪个残基对受体蛋白的表达起关键作用。在第一胞内环中，D2 R和D3 R之间的不同氨基酸被交换，以确定相邻的氨基酸残基是否负责D2 R和D3 R之间的差异。当单个苏氨酸残基突变时，前两个苏氨酸残基变得更重要。然而，所有三个完整的苏氨酸残基对于受体蛋白的适当表达是必需的。D3 R的第一环中三联体苏氨酸残基周围的相邻序列对于受体蛋白在质膜上的正确定位并不重要。D2 R具有比D3 R更灵活的整体构象，可以在胞内区域接受突变残基，这可能是D2 R和D3 R之间信号传导效率的定量差异的部分原因。
The dopamine D2receptor and D3receptor (D2R, D3R) have high homology in both their amino acid composition and signaling pathways. Virtually all signaling pathways reported thus far overlap between the two receptors with the exception that the D3R signals are 2∼5 times less efficient than D2R. Previous studies have suggested that conformational constraints of D3R might be responsible for the poor coupling with the G protein. To this hypothesis, point mutations were introduced into some of the conserved regions between D2R and D3R, and their effects on receptor expression were investigated. Among the four conserved intracellular receptor regions examined (TTT motif in the 1stintracellular loop, SS motif in the 2ndintracellular loop, YxxL and TxxS/xS motifs in the 3rdintracellular loop), a mutation of the Thr-Thr-Thr (TTT) motif in the first intracellular loop or the LxxY motif in the 3rdintracellular loop markedly decreased the level of D3R expression compared with D2R. The TTT motif was further mutated individually or in combination to test which residue plays a critical role on the expression of the receptor proteins. Different amino acids between D2R and D3R in the 1stintracellular loop were exchanged to determine if the adjacent amino acid residues are responsible for the differences between D2R and D3R. The first two threonine residues become more important when the individual threonine residue is mutated. However, all three intact threonine residues are essential for proper expression of the receptor proteins. The neighboring sequences around the triplet threonine residues in the 1stloop of D3R are not important for proper positioning of the receptor proteins on the plasma membrane. It was concluded that D2R has a more flexible overall conformation that can accept mutated residues in the intracellular region than D3R, which might be partly responsible for the quantitative differences in the signaling efficiency between D2R and D3R.
登录
查看更多内容
影响因子：
2.8
作者：
I. von Zabern;B. Hinsch;H. Przyklenk;G. Schmidt;W. Vogt
通讯作者：
W. Vogt
影响因子：
56.9
作者：
ALPER, CA;BALAVITCH, D
通讯作者：
BALAVITCH, D
通过胰蛋白酶激活的人因子 B 和眼镜蛇毒因子复合物激活人补体的热成分。
DOI：
--
发表时间：
1976
期刊：
Japanese Journal of Microbiology
影响因子：
--
作者：
A. Miyama;T. Kato;I. Minoda;T. Ueda;S. Kashiba
通讯作者：
S. Kashiba
DOI：
--
发表时间：
2009
期刊：
Hoppe-Seyler´s Zeitschrift für physiologische Chemie
影响因子：
--
作者：
W. Vogt;L. Dieminger;R. Lynen;G. Schmidt
通讯作者：
G. Schmidt
血清和眼镜蛇毒因子被动溶血：补体诱导膜损伤的新机制。
DOI：
10.1073/pnas.62.2.521
发表时间：
1969
影响因子：
11.1
作者：
R. Pickering;M. Wolfson;R. Good;H. Gewurz
通讯作者：
H. Gewurz