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MAP Kinase Mediated Activation of RSK1 and MK2 Substrate Kinases

63 Pages Posted: 10 Mar 2020 Publication Status: Published

See all articles by Péter Sok

Péter Sok

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Gergő Gógl

Eötvös Loránd University - Department of Biochemistry; University of Strasbourg - Institute of Genetics and of Molecular and Cellular Biology (IGBMC)

Ganesan Kumar

University of Arizona

Anita Alexa

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Neha Singh

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Klára Kirsch

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Anna Sebő

Research Center for Natural Sciences - Biomolecular Interactions Research Group

László Drahos

Research Center for Natural Sciences

Zoltán Gáspári

Peter Pazmany Catholic University

Wolfgang Peti

University of Arizona

Attila Remenyi

Research Center for Natural Sciences - Biomolecular Interactions Research Group

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Abstract

Mitogen activated protein kinases (MAPKs) control essential eukaryotic signaling pathways. While much has been learned about MAPK activation, much less is known about substrate recruitment and specificity. MAPK substrates may be other kinases that are crucial to promote a further diversification of the signaling outcomes. Here, we used a variety of molecular and cellular tools to understand the recruitment of two substrate kinases, RSK1 and MK2, to three MAPKs (ERK2, p38α, ERK5). Unexpectedly, we identified that the formation of specific, structurally and functionally distinct heterodimers allows for different signaling outcomes. Furthermore, we show that small molecule inhibitors likely affect the specific quaternary arrangements of kinase heterodimers and thus affect downstream signaling. Overall, our results demonstrate that MAPKs use heterodimer specific strategies to promote different cellular processes that may be exploited in MAPK based drug development.

Keywords: MAP kinase, protein kinase complex, SAXS, X-ray crystallography, NMR

Suggested Citation

Sok, Péter and Gógl, Gergő and Kumar, Ganesan and Alexa, Anita and Singh, Neha and Kirsch, Klára and Sebő, Anna and Drahos, László and Gáspári, Zoltán and Peti, Wolfgang and Remenyi, Attila, MAP Kinase Mediated Activation of RSK1 and MK2 Substrate Kinases. Available at SSRN: https://ssrn.com/abstract=3547608 or http://dx.doi.org/10.2139/ssrn.3547608
This version of the paper has not been formally peer reviewed.

Péter Sok

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Hungary

Gergő Gógl

Eötvös Loránd University - Department of Biochemistry ( email )

Budapest
Hungary

University of Strasbourg - Institute of Genetics and of Molecular and Cellular Biology (IGBMC) ( email )

1 rue Laurent Fries
Illkirch, 67404
France

Ganesan Kumar

University of Arizona

Department of History
Tucson, AZ 85721
United States

Anita Alexa

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Hungary

Neha Singh

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Hungary

Klára Kirsch

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Hungary

Anna Sebő

Research Center for Natural Sciences - Biomolecular Interactions Research Group

Hungary

László Drahos

Research Center for Natural Sciences

Hungary

Zoltán Gáspári

Peter Pazmany Catholic University

Szentkirályi utca 28
Budapest
Hungary

Wolfgang Peti

University of Arizona

Department of History
Tucson, AZ 85721
United States

Attila Remenyi (Contact Author)

Research Center for Natural Sciences - Biomolecular Interactions Research Group ( email )

Hungary

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