Scaffolding by ERK3 regulates MK5 in development

The EMBO Journal
Stefanie SchumacherMatthias Gaestel

Abstract

Extracellular-regulated kinase 3 (ERK3, MAPK6) is an atypical member of the ERKs, lacking the threonine and tyrosine residues in the activation loop, carrying a unique C-terminal extension and being mainly regulated by its own protein stability and/or by autophosphorylation. Here we show that ERK3 specifically interacts with the MAPK-activated protein kinase 5 (MK5 or PRAK) in vitro and in vivo. Expression of ERK3 in mammalian cells leads to nuclear-cytoplasmic translocation and activation of MK5 and to phosphorylation of both ERK3 and MK5. Remarkably, activation of MK5 is independent of ERK3 enzymatic activity, but depends on its own catalytic activity as well as on a region in the C-terminal extension of ERK3. In mouse embryonic development, mRNA expression patterns of ERK3 and MK5 suggest spatiotemporal coexpression of both kinases. Deletion of MK5 leads to strong reduction of ERK3 protein levels and embryonic lethality at about stage E11, where ERK3 expression in wild-type mice is maximum, indicating a role of this signalling module in development.

References

Jun 15, 1992·FEBS Letters·F A GonzalezR J Davis
Oct 6, 1995·The Journal of Biological Chemistry·A RiesK Kühn
May 26, 1995·The Journal of Biological Chemistry·G ZhouJ E Dixon
Dec 1, 1994·Molecular and Cellular Biology·A X ZhuJ S Flier
Jun 17, 1998·The EMBO Journal·L NewJ Han
Apr 25, 2000·Molecular and Cellular Biology·P SaharinenO Silvennoinen
Jul 21, 2001·EMBO Reports·A NeiningerMatthias Gaestel
Mar 5, 2002·The Journal of Biological Chemistry·Mark K AbeM R Rosner
Dec 10, 2002·Science·G ManningS Sudarsanam
Jan 10, 2003·Nucleic Acids Research·Aron Marchler-BauerStephen H Bryant
Mar 18, 2003·Cellular Signalling·T Tanoue, Eisuke Nishida
Jun 14, 2003·The EMBO Journal·Annette F BaasH C Clevers
Jun 17, 2003·Molecular Biology of the Cell·L NewJiahuai Han
Aug 14, 2003·The Journal of Biological Chemistry·Catherine JulienSylvain Meloche
Oct 16, 2003·Molecular and Cellular Biology·Yu ShiMatthias Gaestel
Oct 18, 2003·Science·Feroz R PapaPeter Walter
Jun 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Philippe P Roux, John Blenis

Citations

Dec 24, 2005·Anatomy and Embryology·David E KlingJay J Schnitzer
Aug 11, 2012·Molecular and Cellular Biochemistry·Benoit BoivinBruce G Allen
Jan 20, 2006·Nature Reviews. Molecular Cell Biology·Matthias Gaestel
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
Jul 24, 2013·The Journal of Experimental Medicine·Kwan T ChowMark S Schlissel
Dec 27, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Efstratios KatsoulidisLeonidas C Platanias
Nov 30, 2011·Molecular and Cellular Biology·Naoto YoshizukaPeiqing Sun
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
Nov 1, 2011·Cell Communication and Signaling : CCS·Jens RauchWalter Kolch
Mar 14, 2009·PLoS Genetics·Beth A HollowayMary C Mullins
Jan 30, 2014·PloS One·Miriam MarquisNathalie Labrecque
Jun 15, 2011·World Journal of Biological Chemistry·Sergiy KostenkoUgo Moens
Dec 7, 2013·The International Journal of Biochemistry & Cell Biology·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
Sep 5, 2006·FEBS Letters·S F Gabby KrensB Ewa Snaar-Jagalska
Sep 21, 2010·Journal of Receptor and Signal Transduction Research·Sergiy KostenkoUgo Moens
Mar 8, 2013·Burns : Journal of the International Society for Burn Injuries·Wei WuMing Zhao
Jul 18, 2012·Journal of Molecular Signaling·Sergiy KostenkoUgo Moens
Apr 17, 2009·The EMBO Journal·Jessica SchwermannMatthias Gaestel
Mar 4, 2014·Journal of Cellular Physiology·Wei WangWeiwen Long
Apr 7, 2006·Molecular and Cellular Endocrinology·Gabriel F AnhêSilvana Bordin
Dec 20, 2005·Biochemical and Biophysical Research Communications·Maoyun SunJianxin Gu
Aug 9, 2005·The International Journal of Biochemistry & Cell Biology·Theresa MikalsenUgo Moens
Jun 17, 2011·The Biochemical Journal·Ratnesh K SrivastavRainer Niedenthal
May 23, 2014·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Byung Dae LeeHyo Deog Rim
Dec 13, 2006·Biochimica Et Biophysica Acta·Phillipe Coulombe, Sylvain Meloche
Jan 19, 2007·Biochimica Et Biophysica Acta·Joseph Avruch
Mar 3, 2017·Scientific Reports·Maria PeranderOle-Morten Seternes
Apr 23, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Sherin Ali NawaitoBruce G Allen
Apr 21, 2018·The Journal of Biological Chemistry·Chika TakahashiEisuke Nishida
Dec 21, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Saurabh SinghRobert M Greene
Mar 7, 2020·Genes & Development·Rabih El-MerahbiGrzegorz Sumara
Jun 16, 2019·International Journal of Molecular Sciences·Monserrat Olea-FloresNapoleón Navarro-Tito
Sep 16, 2006·The Journal of Biological Chemistry·Shashi KantMatthias Gaestel
Sep 24, 2017·IUBMB Life·Pramod Sahadevan, Bruce G Allen
Jan 14, 2020·Bio-protocol·Lobna Elkhadragy, Weiwen Long
Apr 21, 2006·The Journal of Biological Chemistry·Matthew P SaelzlerMark K Abe
Mar 23, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Sherin Ali NawaitoBruce G Allen
Sep 3, 2020·Biomolecules·Toufic Kassouf, Grzegorz Sumara
Sep 15, 2006·The Journal of Biological Chemistry·Espen AbergOle-Morten Seternes
Jan 15, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Denise HornVictor L Ruiz-Perez
Feb 10, 2018·Journal of Molecular Biology·Gustavo Martínez-NoëlPeter M Howley
Aug 21, 2019·Weiwen LongLobna Elkhadragy

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MAP-kinase-activated kinase 5
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