Historical Background
Extracellular signal-regulated kinase 3 (ERK3) and ERK4 are atypical members of the mitogen-activated protein (MAP) kinase family of serine/threonine kinases. The ERK3 and ERK4 genes were originally identified in 1991 and 1992, by homology cloning with probes derived from the MAP kinase ERK1 (Gonzalez et al. 2002; Boulton et al. 1991). In human, ERK3 is encoded by the MAPK6 gene located on chromosome 15q21.2. The MAPK4 gene present on chromosome 18q21.1 encodes ERK4. The high sequence identity of ERK3 and ERK4 proteins and the similar organization of their genes indicate that the two proteins are true paralogs.
Structure of ERK3 and ERK4
ERK3 and ERK4 are related protein kinases of 100 and 70 kDa, respectively, that define a distinct subfamily of MAP kinases (Coulombe and Meloche 2007). They are characterized by the presence of a catalytic kinase...
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References
Aberg E, Perander M, Johansen B, Julien C, Meloche S, Keyse SM, et al. Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4. J Biol Chem. 2006;281:35499–510.
Boulton TG, Nye SH, Robbins DJ, Ip NY, Radzlejewska E, Morgenbesser SD, et al. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991;65:663–75.
Brand F, Schumacher S, Kant S, Menon MB, Simon R, Turgeon B, et al. The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. Mol Cell Biol. 2012;32:2467–78.
Coulombe P, Meloche S. Atypical mitogen-activated protein kinases: structure, regulation and functions. Biochim Biophys Acta. 2007;1773:1376–87.
Coulombe P, Rodier G, Pelletier S, Pellerin J, Meloche S. Rapid turnover of extracellular signal-regulated kinase 3 by the ubiquitin-proteasome pathway defines a novel paradigm of mitogen-activated protein kinase regulation during cellular differentiation. Mol Cell Biol. 2003;23:4542–58.
Déléris P, Trost M, Topisirovic I, Tanguay P-L, Borden KLB, Thibault P, et al. Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. J Biol Chem. 2011;286:6470–8.
Gonzalez FA, Raden DL, Rigby MR, Davis RJ. Heterogeneous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 2002;304:170–8.
Hansen CA, Bartek J, Jensen S. A functional link between the human cell cycle-regulatory phosphatase Cdc14A and the atypical mitogen-activated kinase Erk3. Cell Cycle. 2008;7:325–34.
Kant S, Schumacher S, Singh MK, Kispert A, Kotlyarov A, Gaestel M. Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5. J Biol Chem. 2006;281:35511–9.
Klinger S, Turgeon B, Levesque K, Wood GA, Aagaard-Tillery KM, Meloche S. Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality. Proc Natl Acad Sci USA. 2009;106:16710–5.
Long W, Foulds CE, Qin J, Liu J, Ding C, Lonard DM, et al. ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion. J Clin Invest. 2012;122:1869–80.
Marquis M, Daudelin JF, Boulet S, Sirois J, Crain K, Mathien S, et al. The catalytic activity of the mitogen-activated protein kinase extracellular signal-regulated kinase 3 is required to sustain CD4+ CD8+ thymocyte survival. Mol Cell Biol. 2014;34:3374–87.
Rodriguez J, Pilkington R, Munoz AG, Nguyen LK, Rauch N, Kennedy S, et al. Substrate-trapped interactors of PHD3 and FIH cluster in distinct signaling pathways. Cell Rep. 2016;14:2745–60.
Rousseau J, Klinger S, Rachalski A, Turgeon B, Déléris P, Vigneault E, et al. Targeted inactivation of Mapk4 in mice reveals specific nonredundant functions of Erk3/Erk4 subfamily mitogen-activated protein kinases. Mol Cell Biol. 2010;30:5752–63.
Schumacher S, Laass K, Kant S, Shi Y, Visel A, Gruber AD, et al. Scaffolding by ERK3 regulates MK5 in development. EMBO J. 2004;23:4770–9.
Seternes O-M, Mikalsen T, Johansen B, Michaelsen E, Armstrong CG, Morrice NA, et al. Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. EMBO J. 2004;23:4780–91.
Stöhr N, Köhn M, Lederer M, Glass M, Reinke C, Singer RH, et al. IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev. 2012;26:176–89.
Sun M, Wei Y, Yao L, Xie J, Chen X, Wang H, et al. Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3. Biochem Biophys Res Commun. 2006;340:209–14.
Tanguay P-L, Rodier G, Meloche S. C-terminal domain phosphorylation of ERK3 controlled by Cdk1 and Cdc14 regulates its stability in mitosis. Biochem J. 2010;428:103–11.
Wang W, Bian K, Vallabhaneni S, Zhang B, Wu RC, O’Malley BW, et al. ERK3 promotes endothelial cell functions by upregulating SRC-3/SP1-mediated VEGFR2 expression. J Cell Physiol. 2014;229:1529–37.
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Mathien, S., Soulez, M., Klinger, S., Meloche, S. (2018). Erk3 and Erk4. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_542
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DOI: https://doi.org/10.1007/978-3-319-67199-4_542
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