Immune Functions in Mice Lacking Clnk, an SLP-76-Related Adaptor Expressed in a Subset of Immune Cells
Immune Functions in Mice Lacking Clnk, an SLP-76-Related Adaptor Expressed in a Subset of Immune Cells
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缺乏 Clnk（一种在免疫细胞亚群中表达的 SLP-76 相关接头）的小鼠中的免疫功能
DOI：
10.1128/mcb.24.13.6067-6075.2004
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发表时间：
2004
影响因子：
5.3
通讯作者：
A. Veillette
中科院分区：
文献类型：
--
作者：
O. Utting;B. Sedgmen;T. Watts;Xiaoshun Shi;R. Rottapel;A. Iulianella;D. Lohnes;A. Veillette
SLP-76免疫细胞特异性接头家族由三个不同的成员组成，分别是SLP-76、Blnk和Clnk。它们与免疫受体（如抗原受体和Fc受体）偶联的信号通路有关。先前对基因靶向小鼠和缺陷细胞系的研究表明，SLP-76在t细胞的发育和激活中起着核心作用。此外，它是正常肥大细胞和血小板活化所必需的。相反，Blnk是b细胞发育和激活所必需的。虽然Clnk的确切功能尚不清楚，但据报道，Clnk在肥大细胞，自然杀伤细胞（NK）细胞和先前激活的t细胞中选择性表达。此外，Clnk的异位表达在slp -76缺陷的t细胞系中被证明可以挽救t细胞受体介导的信号转导，这表明Clnk与它的近亲一样，参与免疫受体信号的正向调节。据报道，Clnk对免疫受体信号传导的刺激作用也发生在转染的b细胞和嗜碱性白血病细胞系中。在这里，我们试图通过clink缺陷小鼠的产生来解决clink在免疫细胞中的生理作用。我们的研究结果表明，Clnk对于T细胞、肥大细胞和NK细胞的正常分化和功能是必不可少的。因此，不像它的亲戚，Clnk对正常的免疫功能不是必需的。
ABSTRACT The SLP-76 family of immune cell-specific adaptors is composed of three distinct members named SLP-76, Blnk, and Clnk. They have been implicated in the signaling pathways coupled to immunoreceptors such as the antigen receptors and Fc receptors. Previous studies using gene-targeted mice and deficient cell lines showed that SLP-76 plays a central role in T-cell development and activation. Moreover, it is essential for normal mast cell and platelet activation. In contrast, Blnk is necessary for B-cell development and activation. While the precise function of Clnk is not known, it was reported that Clnk is selectively expressed in mast cells, natural killer (NK) cells, and previously activated T-cells. Moreover, ectopic expression of Clnk was shown to rescue T-cell receptor-mediated signal transduction in an SLP-76-deficient T-cell line, suggesting that, like its relatives, Clnk is involved in the positive regulation of immunoreceptor signaling. Stimulatory effects of Clnk on immunoreceptor signaling were also reported to occur in transfected B-cell and basophil leukemia cell lines. Herein, we attempted to address the physiological role of Clnk in immune cells by the generation of Clnk-deficient mice. The results of our studies demonstrated that Clnk is dispensable for normal differentiation and function of T cells, mast cells, and NK cells. Hence, unlike its relatives, Clnk is not essential for normal immune functions.
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SLP-76 缺陷会损害肥大细胞中高亲和力 IgE 受体的信号传导。
DOI：
--
发表时间：
1999
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Pivniouk,VI;Martin,TR;Lu-Kuo,JM;Katz,HR;Oettgen,HC;Geha,RS
通讯作者：
Geha,RS
影响因子：
56.9
作者：
Clements, JL;Yang, B;Koretzky, GA
通讯作者：
Koretzky, GA
影响因子：
56.9
作者：
Pappu, R;Cheng, AM;Chan, AC
通讯作者：
Chan, AC
影响因子：
56.9
作者：
Yablonski, D;Kuhne, MR;Weiss, A
通讯作者：
Weiss, A