CAST, a novel CD3ε-binding protein transducing activation signal for interleukin-2 production in T cells
CAST, a novel CD3ε-binding protein transducing activation signal for interleukin-2 production in T cells
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DOI：
10.1074/jbc.274.26.18173
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发表时间：
1999-06-25
影响因子：
4.8
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Yamazaki, T;Hamano, Y;Saito, T
通过T细胞受体（TCR）CD 3复合物的抗原识别将信号转导到T细胞中，其调节T细胞的活化、功能和分化。TCR-CD 3复合物由以CD 3 ζ和CD 3 ζ为代表的两个信号传导模块组成。通过CD 3 zeta的信号转导已经被广泛分析，但是通过CD 3 zeta的信号转导，这在未成熟胸腺细胞发育中也是至关重要的，仍然没有被清楚地理解。我们分离了编码一种新的CD 3 ε结合蛋白CAST的cDNA。CAST在体内和体外与CD 3 β特异性相互作用，但不与CD 3 ζ或FcR γ通过CD 3 β的独特膜近端区域相互作用。CAST由包括单个酪氨酸的512个氨基酸组成，并且在TCR刺激时经历酪氨酸磷酸化。两种显性阴性类型的CAST，一个最小的CD 3 ε-结合域和酪氨酸突变体的过表达，强烈抑制NFAT激活和白细胞介素-2的产生。这些结果表明，CAST作为预先形成的TCR复合物的组分，并在TCR刺激时转导活化信号，并代表了通过含CD 3 ε的TCR信号传导模块的新信号传导途径。
Antigen recognition through T cell receptor (TCR)CD3 complex transduces signals into T cells, which regulate activation, function, and differentiation of T cells. The TCR-CD3 complex is composed of two signaling modules represented by CD3 zeta and CD3 epsilon. Signaling through CD3 zeta has been extensively analyzed, but that via CD3 epsilon, which is also crucial in immature thymocyte development, is still not clearly understood. We isolated cDNA encoding a novel CD3 epsilon-binding protein CAST. CAST specifically interacts in vivo and in vitro with CD3 epsilon but not with CD3 zeta or FcR gamma via a unique membrane-proximal region of CD3 epsilon. CAST is composed of 512 amino acids including a single tyrosine and undergoes tyrosine phosphorylation upon TCR stimulation. Overexpression of two dominant-negative types of CAST, a minimum CD3 epsilon-binding domain and a tyrosine-mutant, strongly suppressed NFAT activation and interleukin-2 production. These results demonstrate that CAST serves as a component of preformed TCR complex and transduces activation signals upon TCR stimulation and represents a new signaling pathway via the CD3 epsilon-containing TCR signaling module.