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The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt

Oncogene volume 28, pages 2365–2369 (2009)Cite this article

Abstract

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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Acknowledgements

We thank Dr Nikolay Neznanov for the Ets-reporter construct, Dr Channing Der for RIE-1 cells, Dr George Stark for the MEF cells and Dr Nissim Hay for various Akt-expressing constructs. This work was supported by the Howard Temin Award to ESK, NIH Grant HL071625 to TB and American Heart Association grant 0830326N to PRS.

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  1. P R Somanath and J Vijai: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Cardiology, The Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA

    P R Somanath & T Byzova

  2. Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA

    J Vijai, J V Kichina & E S Kandel

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  1. P R Somanath
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  2. J Vijai
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  3. J V Kichina
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  5. E S Kandel
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Correspondence to E S Kandel.

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Somanath, P., Vijai, J., Kichina, J. et al. The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt. Oncogene 28, 2365–2369 (2009). https://doi.org/10.1038/onc.2009.114

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