In the present paper, we describe multiple levels of cross-talk between the PI3K (phosphoinositide 3-kinase)/Akt and Ras/MAPK (mitogen-activated protein kinase) signalling pathways. Experimental data and computer simulations demonstrate that cross-talk is context-dependent and that both pathways can activate or inhibit each other. Positive influence of the PI3K pathway on the MAPK pathway is most effective at sufficiently low doses of growth factors, whereas negative influence of the MAPK pathway on the PI3K pathway is mostly pronounced at high doses of growth factors. Pathway cross-talk endows a cell with emerging capabilities for processing and decoding signals from multiple receptors activated by different combinations of extracellular cues.
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February 2012
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Conference Article|
January 19 2012
Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance
Edita Aksamitiene;
Edita Aksamitiene
*Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, U.S.A.
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Anatoly Kiyatkin;
Anatoly Kiyatkin
*Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, U.S.A.
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Boris N. Kholodenko
Boris N. Kholodenko
1
*Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, U.S.A.
†Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland
1To whom correspondence should be addressed (email boris.kholodenko@ucd.ie).
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Publisher: Portland Press Ltd
Received:
May 26 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (1): 139–146.
Article history
Received:
May 26 2011
Citation
Edita Aksamitiene, Anatoly Kiyatkin, Boris N. Kholodenko; Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance. Biochem Soc Trans 1 February 2012; 40 (1): 139–146. doi: https://doi.org/10.1042/BST20110609
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