The JNK cascade as a biochemical switch in mammalian cells: Ultrasensitive and all-or-none responses

The JNK cascade as a biochemical switch in mammalian cells: Ultrasensitive and all-or-none responses
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DOI:
10.1016/s0960-9822(03)00083-6
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发表时间:
2003-02-18
期刊:
影响因子:
9.2
通讯作者:
Ferrell, JE
Ferrell, JE
中科院分区:
生物学1区
文献类型:
--
作者:
Bagowski, CP;Besser, J;Ferrell, JE

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JNK蛋白是广泛表达的、进化上保守的MAP激酶,其参与应激反应[1,2]。最近,研究表明非洲爪蟾卵母细胞中的JNK级联反应对分级的瞬时刺激表现出持续的全或无反应[3]。在这里,我们研究了哺乳动物细胞中JNK级联反应的特征。JNK对山梨醇和茴香霉素的稳态反应在HeLa细胞、HEK 293细胞和Jurkat T细胞中被发现是高度超敏感的。JNK反应也是可逆的,而不是持续的,就像在卵母细胞中一样。Jurkat细胞响应于佛波醇肉豆蔻酸酯乙酸酯(PMA)激活其JNK,并且对整个Jurkat细胞群体的响应进行分级。然而,PMA处理的Jurkat细胞亚群的分析显示,JNK和CD69(一种T细胞表面活化标志物)的稳态应答基本上是全或无的。这些研究表明,JNK级联反应通常表现出开关样的反应,以各种刺激。
JNK proteins are ubiquitously expressed, evolutionarily conserved MAP kinases that are involved in stress responses [1, 2]. Recently, it was shown that the JNK cascade in Xenopus oocytes exhibits sustained, all-or-none responses to graded, transient stimuli [3]. Here, we have examined the character of the JNK cascade's response in mammalian cells. The steady-state responses of JNK to sorbitol and anisomycin were found to be highly ultrasensitive in HeLa cells, HEK 293 cells, and Jurkat T cells. The JNK responses were also reversible, not sustained, as was the case in oocytes. Jurkat cells activated their JNK in response to phorbol myristate acetate (PMA), and the response of the entire population of Jurkat cells was graded. However, analysis of subpopulations of the PMA-treated Jurkat cells revealed that the steady-state responses of both JNK and CD69, a T cell surface activation marker, were essentially all-or-none in character. These studies show that the JNK cascade commonly exhibits switch-like responses to a variety of stimuli.