TRANSFORMATION OF MAMMALIAN-CELLS BY CONSTITUTIVELY ACTIVE MAP KINASE KINASE
TRANSFORMATION OF MAMMALIAN-CELLS BY CONSTITUTIVELY ACTIVE MAP KINASE KINASE
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DOI：
10.1126/science.8052857
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发表时间：
1994-08-12
期刊：
影响因子：
56.9
通讯作者：
AHN, NG
中科院分区：
文献类型：
--
作者：
MANSOUR, SJ;MATTEN, WT;AHN, NG
丝裂原活化蛋白（MAP）激酶激酶（MAPKK）在介导细胞对生长和分化因子反应的信号转导途径中激活MAP激酶。已经提出癌基因如ras、src、raf和mos通过延长MAPKK和信号传导途径下游组分的活化状态来转化细胞。为了验证这一假设，设计了组成型活性MAPKK突变体，其基础活性比未磷酸化的野生型激酶高400倍。这些突变体在哺乳动物细胞中的表达激活了AP-1调节的转录。该细胞形成转化灶，在软琼脂中有效生长，并且在裸鼠中具有高度致瘤性。这些发现表明MAPKK的组成性激活足以促进细胞转化。
Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras, src, raf, and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation.