Signal transduction pathways regulated by mitogen-activated extracellular response kinase kinase kinase induce cell death
Signal transduction pathways regulated by mitogen-activated extracellular response kinase kinase kinase induce cell death
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DOI：
10.1074/jbc.271.6.3229
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发表时间：
1996-02-09
影响因子：
4.8
通讯作者：
Johnson, GL
中科院分区：
文献类型：
--
作者：
Johnson, NL;Gardner, AM;Johnson, GL
丝裂原激活/细胞外反应激酶激酶 (MEK) 激酶 (MEKK) 是一种丝氨酸-苏氨酸激酶，可调节顺序蛋白磷酸化途径，导致丝裂原激活蛋白激酶 (MAPK) 激活，包括 Jun 激酶 (JNK)/应激激活蛋白激酶 (SAPK) 家族的成员。在 Swiss 3T3 和 REF52 成纤维细胞中，活化的 MEKK 诱导细胞死亡，包括细胞质收缩、核浓缩和细胞凋亡特征的 DNA 碎片。活化的 MEKK 的表达增强了对紫外线照射的凋亡反应，表明 MEKK 调节的途径使细胞对凋亡刺激敏感。活化的 MEKK 的诱导表达刺激了 c-Myc 和 Elk-1 的反式激活。激活的 Raf（一种激活 MAPK 家族 ERK 成员的丝氨酸-苏氨酸蛋白激酶）会刺激 Elk-1 反式激活，但不会刺激 c-Myc；激活的 Raf 的表达不会诱导任何与 MEKK 介导的细胞死亡相关的细胞变化，因此，MEKK 选择性地调节有助于细胞凋亡反应的信号转导途径。
Mitogen-activated/extracellular response kinase kinase (MEK) kinase (MEKK) is a serine-threonine kinase that regulates sequential protein phosphorylation pathways, leading to the activation of mitogen-activated protein kinases (MAPK), including members of the Jun kinase (JNK)/stress-activated protein kinase (SAPK) family. In Swiss 3T3 and REF52 fibroblasts, activated MEKK induces cell death involving cytoplasmic shrinkage, nuclear condensation, and DNA fragmentation characteristic of apoptosis. Expression of activated MEKK enhanced the apoptotic response to ultraviolet irradiation, indicating that MEKK-regulated pathways sensitize cells to apoptotic stimuli. Inducible expression of activated MEKK stimulated the transactivation of c-Myc and Elk-1. Activated Raf, the serine-threonine pro tein kinase that activates the ERK members of the MAPK family, stimulated Elk-1 transactivation but not c-Myc; expression of activated Raf does not induce any of the cellular changes associated with MEKK-mediated cell death, Thus, MEKK selectively regulates signal transduction pathways that contribute to the apoptotic response.