Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule.
Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule.
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DOI：
10.1038/gene.2008.91
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发表时间：
2009-03
影响因子：
5
通讯作者：
Hurley, C. K.
中科院分区：
文献类型：
--
作者：
VandenBussche, C. J.;Mulrooney, T. J.;Frazier, W. R.;Dakshanamurthy, S.;Hurley, C. K.
使用流式细胞术，荧光显微镜，和受体糖基化状态的检查，我们证明，整个KIR基因座（KIR 2DS 3）-以前假定为表面表达-似乎有一点可观的表面表达转染细胞。这种表型在由三种等位基因变体编码的受体中被注意到，包括常见的KIR 2DS 3 *001等位基因。在两个不同的细胞系中比较KIR 2DS 3的表面表达与更好地研究的KIR 2DS 1分子的表面表达，突变分析鉴定了显著改变细胞表面上存在的分子比例的多个多态性氨基酸残基。需要同时取代定位于前导肽（残基-18、-7）、第二结构域（残基123、150）和跨膜区（残基234）的五个残基以将KIR 2DS 3恢复到KIR 2DS 1的表达水平。KIR 2DS 1到KIR 2DS 3残基的相应同时取代导致表面表达显著降低。分子建模用于预测这些取代如何促成这种表型。受体表面表达的改变可能会影响免疫细胞信号传导的平衡，从而影响对病原体或恶性肿瘤的反应特征。
Using flow cytometry, fluorescent microscopy, and examination of receptor glycosylation status, we demonstrate that an entire KIR locus (KIR2DS3) – previously assumed to be surface expressed – appears to have little appreciable surface expression in transfected cells. This phenotype was noted for receptors encoded by three allelic variants including the common KIR2DS3*001 allele. Comparing the surface expression of KIR2DS3 to that of the better-studied KIR2DS1 molecule in two different cell lines, mutational analysis identified multiple polymorphic amino acid residues that significantly alter the proportion of molecules present on the cell surface. Simultaneous substitution of five residues localized to the leader peptide (residues -18, -7), second domain (residues 123, 150) and transmembrane region (residue 234) was required to restore KIR2DS3 to the expression level of KIR2DS1. Corresponding simultaneous substitutions of KIR2DS1 to the KIR2DS3 residues resulted in dramatically decreased surface expression. Molecular modeling was used to predict how these substitutions contribute to this phenotype. Alterations in receptor surface expression are likely to affect the balance of immune cell signaling impacting the characteristics of the response to pathogens or malignancy.
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影响因子：
64.5
作者：
Lau, Ken S.;Partridge, Emily A.;Dennis, James W.
通讯作者：
Dennis, James W.
影响因子：
6.4
作者：
Drescher, B;Witte, T;Schmidt, RE
通讯作者：
Schmidt, RE
影响因子：
9.8
作者：
Feng J;Call ME;Wucherpfennig KW
通讯作者：
Wucherpfennig KW
DOI：
10.1084/jem.20050499
发表时间：
2005-04-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rajagopalan S;Long EO
通讯作者：
Long EO
影响因子：
64.8
作者：
Fan, QR;Mosyak, L;Wiley, DC
通讯作者：
Wiley, DC