Skip to main content

Erk3 and Erk4

  • Reference work entry
Encyclopedia of Signaling Molecules
  • 183 Accesses

Synonyms

Mapk4 (Erk4); Mapk6 (Erk3)

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 (Boulton et al. 1991; Gonzalez et al. 1992). 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. It is noteworthy that MAPK6 and MAPK4 are the only MAP kinase genes that are restricted to the vertebrate lineage.

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...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • Aberg E, Perander M, Johansen B, Julien C, Meloche S, Keyse SM, Seternes OM. Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4. J Biol Chem. 2006;281:35499–510.

    Article  PubMed  CAS  Google Scholar 

  • Anhe GF, Torrao AS, Nogueira TC, Caperuto LC, Amaral ME, Medina MC, Azevedo-Martins AK, Carpinelli AR, Carvalho CR, Curi R, Boschero AC, Bordin S. ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion. Mol Cell Endocrinol. 2006;251:33–41.

    Article  PubMed  CAS  Google Scholar 

  • Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska E, Morgenbesser SD, DePinho RA, Panayotatos N, Cobb MH, Yancopoulos GD. 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.

    Article  PubMed  CAS  Google Scholar 

  • Cheng M, Boulton TG, Cobb MH. ERK3 is a constitutively nuclear protein kinase. J Biol Chem. 1996;271:8951–8.

    Article  PubMed  CAS  Google Scholar 

  • Coulombe P, Meloche S. Atypical mitogen-activated protein kinases: structure, regulation and functions. Biochim Biophys Acta. 2007;1773:1376–87.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Deleris P, Rousseau J, Coulombe P, Rodier G, Tanguay PL, Meloche S. Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5. J Cell Physiol. 2008;217:778–88.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez FA, Raden DL, Rigby MR, Davis RJ. Heterogenous expression of four MAP kinase isoforms in human tissues. FEBS Lett. 1992;304:170–8.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Julien C, Coulombe P, Meloche S. Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. J Biol Chem. 2003;278:42615–24.

    Article  PubMed  CAS  Google Scholar 

  • 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;281:35511–19.

    Article  PubMed  CAS  Google Scholar 

  • 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;106:16710–15.

    Article  PubMed  CAS  Google Scholar 

  • Perander M, Aberg E, Johansen B, Dreyer B, Guldvik IJ, Outzen H, Keyse SM, Seternes OM. The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5. Biochem J. 2008;411:613–22.

    Article  PubMed  CAS  Google Scholar 

  • Rousseau J, Klinger S, Rachalski A, Turgeon B, Deleris P, Vigneault E, Poirier-Heon JF, Davoli MA, Mechawar N, El Mestikawy S, Cermakian N, Meloche S. Targeted inactivation of Mapk4 in mice reveals specific non-redundant unctions of Erk3/Erk4 subfamily mitogen-activated protein kinases. Mol Cell Biol. 2010;30:5752–63.

    Article  PubMed  CAS  Google Scholar 

  • Schumacher S, Laass K, Kant S, Shi Y, Visel A, Gruber AD, Kotlyarov A, Gaestel M. Scaffolding by ERK3 regulates MK5 in development. EMBO J. 2004;23:4770–9.

    Article  PubMed  CAS  Google Scholar 

  • Seternes OM, Mikalsen T, Johansen B, Michaelsen E, Armstrong CG, Morrice NA, Turgeon B, Meloche S, Moens U, Keyse SM. Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. EMBO J. 2004;23:4780–91.

    Article  PubMed  CAS  Google Scholar 

  • Sun M, Wei Y, Yao L, Xie J, Chen X, Wang H, Jiang J, Gu J. Identification of extracellular signal-regulated kinase 3 as a new interaction partner of cyclin D3. Biochem Biophys Res Commun. 2006;340:209–14.

    Article  PubMed  CAS  Google Scholar 

  • Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, Xie C, Chen J, Deng Q, Yamout M, Dong MQ, Frangou CG, Yates 3rd JR, Wright PE, Han J. PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007;128:295–308.

    Article  PubMed  CAS  Google Scholar 

  • Tanguay PL, 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.

    Article  PubMed  CAS  Google Scholar 

  • Turgeon B, Saba-El-Leil MK, Meloche S. Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa. Biochem J. 2000;346(Pt 1):169–75.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sonia Klinger .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this entry

Cite this entry

Klinger, S., Meloche, S. (2012). Erk3 and Erk4. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_542

Download citation

Publish with us

Policies and ethics