Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5

Journal of Cellular Physiology
Paul DélérisSylvain Meloche

Abstract

Mitogen-activated protein (MAP) kinases are typical examples of protein kinases whose enzymatic activity is mainly controlled by activation loop phosphorylation. The classical MAP kinases ERK1/ERK2, JNK, p38 and ERK5 all contain the conserved Thr-Xxx-Tyr motif in their activation loop that is dually phosphorylated by members of the MAP kinase kinases family. Much less is known about the regulation of the atypical MAP kinases ERK3 and ERK4. These kinases display structural features that distinguish them from other MAP kinases, notably the presence of a single phospho-acceptor site (Ser-Glu-Gly) in the activation loop. Here, we show that ERK3 and ERK4 are phosphorylated in their activation loop in vivo. This phosphorylation is exerted, at least in part, in trans by an upstream cellular kinase. Contrary to classical MAP kinases, activation loop phosphorylation of ERK3 and ERK4 is detected in resting cells and is not further stimulated by strong mitogenic or stress stimuli. However, phosphorylation can be modulated indirectly by interaction with the substrate MAP kinase-activated protein kinase 5 (MK5). Importantly, we found that activation loop phosphorylation of ERK3 and ERK4 stimulates their intrinsic catalytic activity and is r...Continue Reading

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Citations

Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sonia KlingerSylvain Meloche
May 29, 2009·The Journal of Biological Chemistry·Espen AbergOle-Morten Seternes
Feb 15, 2011·The Journal of Biological Chemistry·Alina De la Mota-PeynadoAlexander Beeser
Jan 27, 2012·Genes & Development·Nadine StöhrStefan Hüttelmaier
Mar 5, 2011·Microbiology and Molecular Biology Reviews : MMBR·Marie Cargnello, Philippe P Roux
Apr 17, 2012·The Journal of Clinical Investigation·Weiwen LongBert W O'Malley
Jan 30, 2014·PloS One·Miriam MarquisNathalie Labrecque
Jun 15, 2011·World Journal of Biological Chemistry·Sergiy KostenkoUgo Moens
Mar 22, 2014·International Journal of Molecular Sciences·Inger LindinIngebrigt Sylte
Sep 17, 2013·Theoretical Biology & Medical Modelling·Inger LindinAina Westrheim Ravna
Jul 18, 2012·Journal of Molecular Signaling·Sergiy KostenkoUgo Moens
Mar 4, 2014·Journal of Cellular Physiology·Wei WangWeiwen Long
Dec 19, 2014·Immunology·Julien SiroisNathalie Labrecque
Jun 17, 2011·The Biochemical Journal·Ratnesh K SrivastavRainer Niedenthal
Mar 20, 2010·The Biochemical Journal·Pierre-Luc TanguaySylvain Meloche
Jun 3, 2014·Journal of Ethnopharmacology·Konstantin RozenbergTovit Rosenzweig
Mar 3, 2017·Scientific Reports·Maria PeranderOle-Morten Seternes
Sep 21, 2010·Journal of Receptor and Signal Transduction Research·Sergiy KostenkoUgo Moens
Sep 25, 2017·IUBMB Life·Pramod Sahadevan, Bruce G Allen
Jun 16, 2019·International Journal of Molecular Sciences·Monserrat Olea-FloresNapoleón Navarro-Tito
Oct 30, 2020·International Journal of Molecular Sciences·Martin SchröderApirat Chaikuad
Sep 15, 2020·Bioorganic & Medicinal Chemistry Letters·Ulrich GrädlerChristina Esdar

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