Evidence for MEK-independent pathways regulating the prolonged activation of the ERK-MAP kinases
Evidence for MEK-independent pathways regulating the prolonged activation of the ERK-MAP kinases
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DOI：
10.1038/sj.onc.1201000
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发表时间：
1997-04-10
期刊：
影响因子：
8
通讯作者：
Blenis, J
中科院分区：
文献类型：
--
作者：
Grammer, TC;Blenis, J
丝裂原活化蛋白激酶（MAPK）ERK-1和ERK-2被多种癌基因和细胞外刺激物激活。MAPK参与生长因子/细胞因子受体Ras、Raf和MEK下游的信号级联。然而，MAPK激活比简单的线性途径更复杂，并且这里提出的证据支持多个时间上不同的途径会聚在MAPK上的模型，所述多个时间上不同的途径被各种刺激和细胞类型差异地利用。除了MEK依赖的MAPK激活，我们提供的证据MEK的独立调节的MAPK。我们的研究结果表明，磷脂酰肌醇-3-激酶（PI（3）K）或传统的蛋白激酶C亚型（cPKCs）部分有助于MEK依赖性激活。重要的是，我们还发现，PI 3 K和cPKCs发挥了重要作用，MEK独立的，延长MAPK激活血小板源性生长因子信号。这一发现是令人感兴趣的，因为其他人已经将MAPK的维持激活与细胞增殖和分化的调节相关联。
The mitogen-activated protein kinases (MAPKs) ERK-1 and ERK-2 are activated by a wide variety of oncogenes and extracellular stimuli. The MAPKs participate in a signalling cascade downstream of growth factor/cytokine receptors, Ras, Raf, and MEK. However, MAPK activation is more complicated than a simple linear pathway, and the evidence presented here supports a model of multiple, temporally distinct pathways converging on MAPK which are differentially utilized by various stimuli and cell types. In addition to MEK-dependent MAPK activation, we provide evidence for MEK-independent regulation of the MAPKs. Our results suggest that phosphatidylinositol-3-kinases (PI(3)K) or conventional protein kinase C isoforms (cPKCs) partially contribute to MEK-dependent activation. Importantly, we also find that PI3K and cPKCs play a major role in the MEK-independent, prolonged MAPK activation by platelet-derived growth factor signalling. This finding is of interest as the maintained activation of MAPK has been correlated by others to the regulation of cell proliferation and differentiation.