Kuroyama Hiroyuki, Ikeda Tohru, Kasai Michiyuki, Yamasaki Sho, Tatsumi Masashi, Utsuyama Masanori, Saito Takashi, Hirokawa Katsuiku
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Biochem Biophys Res Commun. 2004 Mar 19;315(4):935-41. doi: 10.1016/j.bbrc.2004.01.127.
We identified a novel cDNA encoding truncated ZAP-70, which lacked the SH2 domain and a part of interdomain B, and named it truncated ZAP kinase (TZK). TZK was expressed in the thymus, spleen, and lymph nodes with ZAP-70. TZK was expressed in CD44+CD25- thymocytes up to mature T cells, but ZAP-70 was not expressed in CD44+CD25- or CD44+CD25+ thymocytes. ZAP-70 or TZK was transfected into P116 cells derived from a Jurkat T-cell line deficient in ZAP-70. The P116 cells with ZAP-70 induced the T-cell receptor-mediated signal transduction, but the cells expressing TZK did not. While ZAP-70 was accumulated at the immune synapse, TZK was not. Meanwhile, impaired phosphorylation of SLP-76, one of the substrates of ZAP-70, in P116 cells upon pervanadate stimulation was rescued in the cells expressing TZK. These findings show that TZK is a novel isoform of ZAP-70, which is expressed in pre-T-cell receptor-minus thymocytes and functions as a kinase not associated with T-cell receptor.
我们鉴定出一种编码截短型ZAP-70的新cDNA，其缺少SH2结构域和结构域B的一部分，我们将其命名为截短型ZAP激酶（TZK）。TZK与ZAP-70一起在胸腺、脾脏和淋巴结中表达。TZK在从CD44+CD25-胸腺细胞到成熟T细胞中均有表达，但ZAP-70在CD44+CD25-或CD44+CD25+胸腺细胞中不表达。将ZAP-70或TZK转染到源自缺乏ZAP-70的Jurkat T细胞系的P116细胞中。转染ZAP-70的P116细胞可诱导T细胞受体介导的信号转导，但表达TZK的细胞则不能。ZAP-70在免疫突触处聚集，而TZK则不然。同时，过氧钒酸盐刺激后P116细胞中ZAP-70的底物之一SLP-76的磷酸化受损，而在表达TZK的细胞中得以挽救。这些发现表明，TZK是ZAP-70的一种新型异构体，在缺乏前T细胞受体的胸腺细胞中表达，并且作为一种与T细胞受体无关的激酶发挥作用。
