van Oers N S, von Boehmer H, Weiss A
Department of Medicine, University of California, San Francisco 94143, USA.
J Exp Med. 1995 Nov 1;182(5):1585-90. doi: 10.1084/jem.182.5.1585.
The pre-T cell receptor (TCR) complex regulates early T cell development and consists of a heterodimer of the TCR-beta subunit in association with the pre-TCR-alpha chain. Notably, in contrast to alpha/beta-expressing T cells, several studies suggested that the TCR-zeta chain is not stably associated with this pre-TCR complex. To examine the proximal signaling processes mediated by the pre-TCR complex and the role of the TCR-zeta chain in these processes, we stimulated pre-TCR-expressing cells and analyzed the interactions of the TCR/CD3 invariant chains with the Syk/ZAP-70 family of protein tyrosine kinases. Stimulation of the pre-TCR complex led to the tyrosine phosphorylation of the CD3 epsilon and TCR-zeta chains, as well as the phosphorylation and association of ZAP-70 and Syk with phosphorylated CD3 epsilon and TCR-zeta. These results demonstrate that the pre-TCR complex is functionally coupled to the TCR-zeta subunit and to the ZAP-70 and Syk protein tyrosine kinases.
前T细胞受体(TCR)复合物调节早期T细胞发育,由TCR-β亚基与前TCR-α链的异二聚体组成。值得注意的是,与表达α/β的T细胞不同,多项研究表明TCR-ζ链并不稳定地与该前TCR复合物相关联。为了研究前TCR复合物介导的近端信号转导过程以及TCR-ζ链在这些过程中的作用,我们刺激表达前TCR的细胞,并分析TCR/CD3恒定链与Syk/ZAP-70家族蛋白酪氨酸激酶的相互作用。前TCR复合物的刺激导致CD3ε和TCR-ζ链的酪氨酸磷酸化,以及ZAP-70和Syk与磷酸化的CD3ε和TCR-ζ的磷酸化和结合。这些结果表明,前TCR复合物在功能上与TCR-ζ亚基以及ZAP-70和Syk蛋白酪氨酸激酶偶联。