Johnson N L, Gardner A M, Diener K M, Lange-Carter C A, Gleavy J, Jarpe M B, Minden A, Karin M, Zon L I, Johnson G L
Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
J Biol Chem. 1996 Feb 9;271(6):3229-37. doi: 10.1074/jbc.271.6.3229.
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 protein 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.
丝裂原活化/细胞外反应激酶激酶（MEK）激酶（MEKK）是一种丝氨酸-苏氨酸激酶，它调节一系列蛋白质磷酸化途径，导致丝裂原活化蛋白激酶（MAPK）的激活，包括Jun激酶（JNK）/应激激活蛋白激酶（SAPK）家族的成员。在瑞士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、核浓缩以及凋亡特有的DNA片段化。活化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MEKK的可诱导表达刺激了c-Myc和Elk-1的反式激活。活化的Raf，即激活MAPK家族ERK成员的丝氨酸-苏氨酸蛋白激酶，刺激了Elk-1的反式激活，但不刺激c-Myc；活化Raf的表达不会诱导与MEKK介导的细胞死亡相关的任何细胞变化。因此，MEKK选择性地调节有助于凋亡反应的信号转导途径。
