CD28 and the tyrosine kinase Lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein Rap1
CD28 and the tyrosine kinase Lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein Rap1
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DOI：
10.1128/mcb.20.22.8409-8419.2000
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发表时间：
2000-11-01
影响因子：
5.3
通讯作者：
Stork, PJS
中科院分区：
文献类型：
--
作者：
Carey, KD;Dillon, TJ;Stork, PJS
通过激活T细胞受体（TCR）来实现T细胞增殖需要同时参与辅助共刺激分子以实现完全激活。研究最充分的共刺激分子CD28，部分通过增强TCR到有丝分裂原活化蛋白激酶级联的信号来达到这些效果。我们在这里表明，tcr介导的MAP激酶细胞外信号调节激酶（ERKs）的刺激受到Ras拮抗剂Rap1的激活的限制。CD28通过阻断Rap1的作用增加ERK信号。CD28抑制Rap1激活是因为它选择性地刺激外源性Rap1 GTPase活性。CD28刺激Rap1 GTPase活性的能力依赖于酪氨酸激酶Lck。我们的研究结果表明，CD28介导的Rap1 gtpase激活蛋白的激活可以帮助解释CD28共刺激过程中ERKs的增加。
Proliferation of T cells via activation of the T-cell receptor (TCR) requires concurrent engagement of accessory costimulatory molecules to achieve full activation. The best-studied costimulatory molecule, CD28, achieves these effects, in part, by augmenting signals from the TCR to the mitogen-activated protein (MAP) kinase cascade. We show here that TCR-mediated stimulation of MAP kinase extracellular-signal-regulated kinases (ERKs) is limited by activation of the Ras antagonist Rap1. CD28 increases ERK signaling by blocking Rap1 action. CD28 inhibits Rap1 activation because it selectively stimulates an extrinsic Rap1 GTPase activity. The ability of CD28 to stimulate Rap1 GTPase activity was dependent on the tyrosine kinase Lck. Our results suggest that CD28-mediated Rap1 GTPase-activating protein activation can help explain the augmentation of ERKs during CD28 costimulation.