Grammer T C, Blenis J
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Oncogene. 1997 Apr 10;14(14):1635-42. doi: 10.1038/sj.onc.1201000.
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.
丝裂原活化蛋白激酶（MAPKs）中的ERK-1和ERK-2可被多种癌基因和细胞外刺激激活。MAPKs参与生长因子/细胞因子受体、Ras、Raf和MEK下游的信号级联反应。然而，MAPK的激活比简单的线性途径更为复杂，此处提供的证据支持一种模型，即多种在时间上不同的途径汇聚于MAPK，各种刺激和细胞类型对其有不同的利用方式。除了MEK依赖的MAPK激活外，我们还提供了MAPKs的MEK非依赖调节的证据。我们的结果表明，磷脂酰肌醇-3-激酶（PI(3)K）或传统蛋白激酶C亚型（cPKCs）部分参与了MEK依赖的激活。重要的是，我们还发现PI3K和cPKCs在血小板衍生生长因子信号传导导致的MEK非依赖、持久的MAPK激活中起主要作用。这一发现很有意义，因为其他人已将MAPK的持续激活与细胞增殖和分化的调节联系起来。
