Genetic analysis of SH2D4A, a novel adapter protein related to T cell-specific adapter and adapter protein in lymphocytes of unknown function, reveals a redundant function in T cells.
Genetic analysis of SH2D4A, a novel adapter protein related to T cell-specific adapter and adapter protein in lymphocytes of unknown function, reveals a redundant function in T cells.
复制标题
DOI：
10.4049/jimmunol.181.3.2019
复制
发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
King, Philip D.
中科院分区：
文献类型：
--
作者：
Lapinski, Philip E.;Oliver, Jennifer A.;Kamen, Lynn A.;Hughes, Elizabeth D.;Saunders, Thomas L.;King, Philip D.
T细胞特异性接头蛋白（TSAd）和淋巴细胞中未知功能的接头蛋白（ALX）是两种相关的含有src-同源性-2（SH 2）结构域的信号转导接头分子，它们都被证明在T细胞中调节TCR信号转导。TSAd是T细胞中正常TCR诱导的IL-2和其他细胞因子合成所需的，并且至少部分地通过在TCR信号级联开始时促进LCK蛋白酪氨酸激酶的活化而起作用。相比之下，ALX通过尚未确定的机制作为TCR诱导的IL-2合成的负调节剂发挥作用。在此，我们报告了一种新的T细胞表达的衔接蛋白命名为SH 2D 4A，它含有一个SH 2结构域，是高度同源的TSAd和ALX SH 2结构域，并与这些适配器共享其他结构特征。为了检测SH 2D 4A在T细胞中的功能，我们通过胚胎干细胞中的同源重组产生了SH 2D 4A缺陷小鼠。在这些小鼠中发现T细胞发育、稳态、增殖和功能都是正常的。此外，人T细胞中SH 2D 4A表达的敲低不影响其功能。我们得出结论，与TSAd和ALX相反，SH 2D 4A在T细胞中不参与TCR信号转导。
T cell-specific adapter protein (TSAd) and adapter protein in lymphocytes of unknown function (ALX) are two related src-homology-2 (SH2) domain-containing signaling adapter molecules that have both been shown to regulate TCR signal transduction in T cells. TSAd is required for normal TCR-induced synthesis of IL-2 and other cytokines in T cells and acts at least in part by promoting activation of the LCK protein tyrosine kinase at the outset of the TCR signaling cascade. By contrast, ALX functions as a negative-regulator of TCR-induced IL-2 synthesis through as yet undetermined mechanisms. Herein, we report a novel T cell-expressed adapter protein named SH2D4A that contains an SH2 domain that is highly homologous to the TSAd and ALX SH2 domains and which shares other structural features with these adapters. To examine the function of SH2D4A in T cells we produced SH2D4A-deficient mice by homologous recombination in embryonic stem cells. T cell development, homeostasis, proliferation and function were all found to be normal in these mice. Furthermore, knockdown of SH2D4A expression in human T cells did not impact upon their function. We conclude that in contrast to TSAd and ALX, SH2D4A is dispensable for TCR signal transduction in T cells.
登录
查看更多内容
影响因子：
--
作者：
Charles, Michael A.;Saunders, Thomas L.;Gordon, David F.
通讯作者：
Gordon, David F.
DOI：
10.1084/jem.20051637
发表时间：
2006-02-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Marti, F;King, PD
通讯作者：
King, PD
影响因子：
5.3
作者：
Perchonock, Claire E.;Fernando, Melissa C.;Shapiro, Virginia Smith
通讯作者：
Shapiro, Virginia Smith
DOI：
10.1084/jem.190.11.1657
发表时间：
1999-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Rajagopal K;Sommers CL;Decker DC;Mitchell EO;Korthauer U;Sperling AI;Kozak CA;Love PE;Bluestone JA
通讯作者：
Bluestone JA