LIGATION OF THE T-CELL RECEPTOR COMPLEX RESULTS IN ACTIVATION OF THE RAS/RAF-1/MEK/MAPK CASCADE IN HUMAN T-LYMPHOCYTES
LIGATION OF THE T-CELL RECEPTOR COMPLEX RESULTS IN ACTIVATION OF THE RAS/RAF-1/MEK/MAPK CASCADE IN HUMAN T-LYMPHOCYTES
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DOI：
10.1172/jci117209
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发表时间：
1994-05-01
影响因子：
15.9
通讯作者：
GELFAND, EW
中科院分区：
文献类型：
--
作者：
FRANKLIN, RA;TORDAI, A;GELFAND, EW
使用针对 T 细胞受体复合物的抗体刺激 T 细胞会导致丝裂原相关蛋白激酶 (MAPK) 的激活。在其他细胞类型中已描述了两种可导致 MAPK 激活的途径。这些途径之一涉及 Ras 的激活，从而导致 Raf-1 的激活，以及随后的 MEK（MAPK 或 ERK 激酶）的激活。检查了 T 细胞中该通路对抗 CD3 或佛波醇肉豆蔻酸酯 (PMA) 介导的 MAPK 激活的贡献。我们在导致 MAPK 激活的途径中检测到 Raf-1 和 MEK 对其底物（Raf-1 的 MEK 和 MEK 的 MAPK）的激酶活性。用抗 CD3 抗体或 PMA 刺激 T 细胞会导致 Ras 和 Raf-1 快速激活。 MEK 对激酶活性或失活重组 MAPK 的活性在刺激后也会增加。此外，这些细胞中 MAPK 和 p90(rsk) 均被激活。我们认为，T 细胞受体复合物连接刺激的 T 淋巴细胞中 Ras/Raf-1/MEK 级联反应会激活 MAPK 并随后激活核糖体 S6 激酶 (p90(rsk))。
Stimulation of T cells with antibodies directed towards the T cell receptor complex results in the activation of mitogen-associated protein kinase (MAPK). Two pathways have been described in other cell types that can lead to MAPK activation. One of these pathways involves the activation of Ras, leading to the activation of Raf-1, and the subsequent activation of MEK (MAPK or ERK kinase). The contribution of this pathway in T cells for anti-CD3 or phorbol myristate acetate (PMA)-mediated MAPK activation was examined. We detected the kinase activities of Raf-1 and MEK towards their substrates (MEK for Raf-1 and MAPK for MEK) in this pathway leading to the activation of MAPK. Stimulation of the T cells with either anti-CD3 antibody or PMA resulted in a rapid activation of both Ras and Raf-1. MEK activity towards kinase-active or -inactive recombinant MAPK also increased upon stimulation. In addition, both MAPK and p90(rsk) were activated in these cells. We suggest that activation of MAPK and the subsequent activation of ribosomal S6 kinase (p90(rsk)) occurs by the Ras/Raf-1/MEK cascade in T lymphocytes stimulated by ligation of the T cell receptor complex.