The RAF–MEK–ERK mitogen-activated protein kinase (MAPK) cascade is aberrantly activated in a diverse set of human cancers and the RASopathy group of genetic developmental disorders. This protein kinase cascade is one of the most intensely studied cellular signaling networks and has been frequently targeted by the pharmaceutical industry, with more than 30 inhibitors either approved or under clinical evaluation. The ERK–MAPK cascade was originally depicted as a serial and linear, unidirectional pathway that relays extracellular signals, such as mitogenic stimuli, through the cytoplasm to the nucleus. However, we now appreciate that this three-tiered protein kinase cascade is a central core of a complex network with dynamic signaling inputs and outputs and autoregulatory loops. Despite our considerable advances in understanding the ERK–MAPK network, the ability of cancer cells to adapt to the inhibition of key nodes reveals a level of complexity that remains to be fully understood. In this review, we summarize important developments in our understanding of the ERK–MAPK network and identify unresolved issues for ongoing and future study.
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On the implications of the copper co-factor in lytic polysaccharide monooxygenase. A brief overview of structure, oxygen activation and application as bioindustrial process tools for decomposition of lignocellulose. Further information can be found in the review by Ipsen and colleagues (pages 531–540). Image provided by Katja Johansen.
Review Article|
February 05 2021
The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction
Jennifer E. Klomp
;
Jennifer E. Klomp
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
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Jeff A. Klomp
;
Jeff A. Klomp
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
2Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
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Channing J. Der
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
2Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
Correspondence: Channing J. Der (cjder@med.unc.edu)
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Publisher: Portland Press Ltd
Received:
October 13 2020
Revision Received:
December 30 2020
Accepted:
January 08 2021
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2021
Biochem Soc Trans (2021) 49 (1): 253–267.
Article history
Received:
October 13 2020
Revision Received:
December 30 2020
Accepted:
January 08 2021
Citation
Jennifer E. Klomp, Jeff A. Klomp, Channing J. Der; The ERK mitogen-activated protein kinase signaling network: the final frontier in RAS signal transduction. Biochem Soc Trans 26 February 2021; 49 (1): 253–267. doi: https://doi.org/10.1042/BST20200507
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