The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt.
The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt.
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DOI：
10.1038/onc.2009.114
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发表时间：
2009-06-25
期刊：
影响因子：
8
通讯作者：
Kandel, E. S.
中科院分区：
文献类型：
--
作者：
Somanath, P. R.;Vijai, J.;Kichina, J. V.;Byzova, T.;Kandel, E. S.
关键词：
蛋白激酶B(Protein Kinase B，又称Akt)的活性在人类恶性肿瘤中普遍升高，在肿瘤转化中起关键作用。Akt和丝裂原活化蛋白激酶级联反应之间的关系仍然存在争议，而丝裂原活化蛋白激酶级联反应也经常与肿瘤发生有关。我们在这里报告了Akt和CRAF在致癌转化中合作的例子，伴随着细胞外信号调节的丝裂原活化蛋白激酶活性的提高。Akt对细胞外信号调节激酶的影响依赖于p21激活的激酶(PAK)的状态。重要的是，PAK功能的破坏不仅使Akt的激活与细胞外信号调节激酶的激活解偶联，而且极大地降低了Akt作为转化癌基因的能力。对于Akt过度活跃的恶性肿瘤，我们的观察支持PAK-1作为潜在的治疗干预靶点的作用。
The activity of protein kinase B, also known as Akt, is commonly elevated in human malignancies and plays a crucial role in oncogenic transformation. The relationship between Akt and the mitogen-activated protein kinase cascade, which is also frequently associated with oncogenesis, remains controversial. We report here examples of cooperation between Akt and cRaf in oncogenic transformation, which was accompanied by elevated activity of extracellular signal-regulated mitogen-activated protein kinases. The effect of Akt on extracellular signal-regulated kinases depended on the status of p21-activated kinase (PAK). Importantly, disruption of the function of PAK not only uncoupled the activation of Akt from that of extracellular signal-regulated kinases, but also greatly reduced the capacity of Akt to act as a transforming oncogene. For the malignancies with hyperactive Akt, our observations support the role for PAK-1 as a potential target for therapeutic intervention.
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