Straus D B, Weiss A
Department of Medicine, University of California, San Francisco 94143.
J Exp Med. 1993 Nov 1;178(5):1523-30. doi: 10.1084/jem.178.5.1523.
Recent work indicates that signaling events resulting from stimulation of the T cell antigen receptor (TCR) can be initiated by the CD3 complex (gamma, delta, epsilon) as well as the zeta chains of the receptor. To help characterize the signaling function of CD3 we examined its associated tyrosine kinase activity since induction of tyrosine phosphorylation is one of the earliest signaling events. Our results indicate that at least two kinases, lck and ZAP-70, contribute to the CD3-associated kinase activity. A likely target of this activity is the CD3 complex itself since we observed that TCR stimulation resulted in rapid tyrosine phosphorylation of the CD3 epsilon and delta chains. To examine the function of the CD3 epsilon chain in particular, we constructed a chimera that fused the extracellular and transmembrane domains of CD8 to the cytoplasmic domain of CD3 epsilon. This chimera demonstrated that CD3 epsilon was independently capable of associating with proteins having tyrosine kinase activity, including ZAP-70. Our results show that the kinase activity that associates with the CD3 complex has characteristics that are quite similar to the previously characterized zeta-associated kinase activity. This finding suggests that both these components of the TCR initiate signaling events using a common mechanism. However, differences in their signaling function could result from recognition of distinct substrates.
近期研究表明，T细胞抗原受体（TCR）受刺激引发的信号事件可由CD3复合体（γ、δ、ε链）以及受体的ζ链启动。为了帮助阐明CD3的信号功能，我们检测了其相关的酪氨酸激酶活性，因为酪氨酸磷酸化的诱导是最早的信号事件之一。我们的结果表明，至少有两种激酶，即lck和ZAP - 70，参与了与CD3相关的激酶活性。这种活性的一个可能靶点是CD3复合体本身，因为我们观察到TCR刺激导致CD3 ε链和δ链迅速发生酪氨酸磷酸化。为了特别研究CD3 ε链的功能，我们构建了一种嵌合体，将CD8的胞外和跨膜结构域与CD3 ε链的胞质结构域融合。这种嵌合体表明，CD3 ε链能够独立地与具有酪氨酸激酶活性的蛋白质结合，包括ZAP - 70。我们的结果表明，与CD3复合体相关的激酶活性具有与先前鉴定的ζ链相关激酶活性非常相似的特征。这一发现表明，TCR的这两个组分利用共同的机制启动信号事件。然而，它们信号功能的差异可能源于对不同底物的识别。
