Non-T cell activation linker (NTAL):: A transmembrane adaptor protein involved in immunoreceptor signaling
Non-T cell activation linker (NTAL):: A transmembrane adaptor protein involved in immunoreceptor signaling
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DOI：
10.1084/jem.20021405
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发表时间：
2002-12-16
影响因子：
15.3
通讯作者：
Horejsí, V
中科院分区：
文献类型：
--
作者：
Brdicka, T;Imrich, M;Horejsí, V
通过其抗原特异性T细胞受体（TCR）活化T淋巴细胞所必需的关键分子是跨膜衔接蛋白LAT（用于活化T细胞的接头）。在TCR接合后，LAT迅速酪氨酸磷酸化，然后充当组织多组分复合物的支架，该复合物对于诱导信号级联的进一步下游步骤是必不可少的。在这里，我们描述了一种新的跨膜衔接蛋白的鉴定和初步表征，该蛋白在结构上和进化上与LAT相关，并在B淋巴细胞、自然杀伤（NK）细胞、单核细胞和肥大细胞中表达，但不在静息T淋巴细胞中表达。这种新的跨膜接头蛋白，称为NTAL（非T细胞活化接头）是以前鉴定的WBSCR 5基因的产物，迄今为止功能未知。NTAL在与骨髓细胞的B细胞受体（BCR）或高亲和力Fc γ-和Fc ε-受体交联后迅速酪氨酸磷酸化，然后与细胞质信号分子Grb 2、Sos 1、Gab 1和c-Cb 1缔合。在LAT缺陷型T细胞系J.CaM2.5中表达的NTAL变得酪氨酸磷酸化，并在TCR/CD 3交联后挽救Erk 1/2的激活和细胞质钙水平的最小瞬时升高。因此，NTAL似乎是LAT在非T细胞中的结构和功能同源物。
A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non-T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcy- and Fcs-receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cb1. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non-T cells.