INTERACTION OF SHC WITH THE ZETA-CHAIN OF THE T-CELL RECEPTOR UPON T-CELL ACTIVATION

INTERACTION OF SHC WITH THE ZETA-CHAIN OF THE T-CELL RECEPTOR UPON T-CELL ACTIVATION
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DOI:
10.1126/science.8235613
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发表时间:
1993-11-05
期刊:
影响因子:
56.9
通讯作者:
BURAKOFF, SJ
BURAKOFF, SJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
RAVICHANDRAN, KS;LEE, KK;BURAKOFF, SJ

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shc 癌基因产物被 Src 家族激酶酪氨酸磷酸化,磷酸化后与衔接蛋白 Grb2(生长因子受体结合蛋白 2)相互作用。反过来,Grb2 与 Ras、mSOS 的鸟嘌呤核苷酸交换因子相互作用。由于多种 Src 家族激酶参与 T 细胞激活,并且 Shc 功能位于 Ras 上游,因此检查了 Shc 在 T 细胞信号传导中的作用。 Shc 通过 T 细胞受体 (TCR) 激活后在酪氨酸上磷酸化,随后与 Grb2 和 mSOS 相互作用。 Shc 的 Src 同源区 2 (SH2) 结构域直接与 TCR 的酪氨酸磷酸化 zeta 链相互作用。因此,Shc 可能将 TCR 激活与 Ras 信号通路偶联。
The shc oncogene product is tyrosine-phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb2 (growth factor receptor-bound protein 2). In turn, Grb2 interacts with the guanine nucleotide exchange factor for Ras, mSOS. Because several Src family kinases participate in T cell activation and Shc functions upstream of Ras, the role of Shc in T cell signaling was examined. Shc was phosphorylated on tyrosine after activation through the T cell receptor (TCR), and subsequently interacted with Grb2 and mSOS. The Src homology region 2 (SH2) domain of Shc directly interacted with the tyrosine-phosphorylated zeta chain of the TCR. Thus, Shc may couple TCR activation to the Ras signaling pathway.