DIFFERENTIAL ACTIVATION OF ERK AND JNK MITOGEN-ACTIVATED PROTEIN-KINASES BY RAF-1 AND MEKK
DIFFERENTIAL ACTIVATION OF ERK AND JNK MITOGEN-ACTIVATED PROTEIN-KINASES BY RAF-1 AND MEKK
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DOI：
10.1126/science.7992057
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发表时间：
1994-12-09
期刊：
影响因子：
56.9
通讯作者：
KARIN, M
中科院分区：
文献类型：
--
作者：
MINDEN, A;LIN, A;KARIN, M
生长因子激活丝裂原活化蛋白激酶（MAPK），包括细胞外信号调节激酶（ERK）和Jun激酶（JNK）。虽然从生长因子受体到ERK的信号级联反应已经相对较好地理解，但导致JNK活化的途径更加模糊。表皮生长因子（EGF）或神经生长因子（NGF）激活JNK依赖于H-Ras激活，而肿瘤坏死因子α（TNF-α）激活JNK则不依赖于Ras。Ras激活两种蛋白激酶Raf-1和MEK（MAPK或ERK激酶）激酶（MEKK）。Raf-1直接参与ERK的激活，但不参与JNK的激活，而MEKK参与JNK的激活，但仅在过表达后才引起ERK的激活。这些结果表明存在两种不同的Ras依赖性MAPK通路-一种由Raf-1启动导致ERK活化，另一种由MEKK启动导致JNK活化。
Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor alpha (TNF-alpha) was Ras-independent. Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. These results demonstrate the existence of two distinct Ras-dependent MAPK cascades-one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation.