Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption
Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption
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DOI：
10.1126/science.282.5395.1911
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发表时间：
1998-12-04
期刊：
影响因子：
56.9
通讯作者：
Johnson, GL
中科院分区：
文献类型：
--
作者：
Yujiri, T;Sather, S;Johnson, GL
有针对性地破坏编码MEK激酶1 （MEKK1）的基因，MEKK1是一种丝裂原活化蛋白激酶（MAPK）激酶，定义了其在调节MAPK通路和细胞存活中的功能。小鼠MEKK1（-/-）胚胎干细胞对微管破坏和冷应激的c-Jun氨基末端激酶（INK）反应缺失或改变，但在热休克、大霉素和紫外线照射下正常激活JNK。在MEKK1（-/-）细胞中，JNK的激活丧失，细胞外信号调节蛋白激酶（ERK）的激活减少，以响应高渗透压和血清因子。MEKK1表达的缺失导致细胞对高渗透压和微管破坏的更大凋亡反应。当被改变细胞形状和细胞骨架的特定应激激活时，MEKK1发出信号以保护细胞免于凋亡。
Targeted disruption of the gene encoding MEK kinase 1 (MEKK1), a mitogen-activated protein kinase (MAPK) kinase kinase, defined its function in the regulation of MAPK pathways and cell survival. MEKK1(-/-) embryonic stem cells from mice had Lost or altered responses of the c-Jun amino-terminal kinase (INK) to microtubule disruption and cold stress but activated JNK normally in response to heat shock, anisomycin, and ultraviolet irradiation. Activation of JNK was Lost and that of extracellular signal-regulated protein kinase (ERK) was diminished in response to hyperosmolarity and serum factors in MEKK1(-/-) cells. Loss of MEKK1 expression resulted in a greater apoptotic response of cells to hyperosmolarity and microtubule disruption. When activated by specific stresses that alter cell shape and the cytoskeleton, MEKK1 Signals to protect cells from apoptosis.