Skip to main content
SpringerLink
Log in

MAP Kinase-Activated Protein Kinase 5 (MK5)

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 182 Accesses

Synonyms

MAPKAP kinase 5; MAPKAPK 5; PRAK

Historical Background

Murine and human MK5 cDNAs were initially isolated in 1998 in two independent screens for proteins with sequence homology to MK2 (New et al. 1998; Ni et al. 1998). The novel 54-kDa kinase ubiquitously expressed in all tissues displayed 45% amino acid identity to MK2. Both groups showed that MK5 could be phosphorylated and activated in vitro by the p38 MAP kinase, as detected by 32P incorporation into a substrate peptide (KKRPQRATSNVFS) or Hsp25 (HSPB1). New et al. named this kinase as p38-regulated and activated kinase or PRAK to emphasize its integration into the p38 pathway. More recently, MK5 has also been shown to interact with the atypical MAP kinases, ERK3 (MAPK6) and ERK4 (MAPK4), and these kinases are also involved in the phosphorylation and activation of MK5 (Schumacher et al. 2004; Seternes et al. 2004; Aberg et al. 2006; Kant et al. 2006). An MK5 gene does not appear to be present in either C. elegans or Drosophila...

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

Access this chapter

Log in via an institution

Institutional subscriptions

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. doi:10.1074/jbc.M606225200.

    Article  CAS  PubMed  Google Scholar 

  • 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. doi:10.1128/MCB.06633-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chow KT, Timblin GA, McWhirter SM, Schlissel MS. MK5 activates Rag transcription via Foxo1 in developing B cells. J Exp Med. 2013;210:1621–34. doi:10.1084/jem.20130498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De la Mota-Peynado A, Chernoff J, Beeser A. Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity. J Biol Chem. 2011;286:13603–11. doi:10.1074/jbc.M110.181743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deleris P, Trost M, Topisirovic I, Tanguay PL, Borden KL, 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. doi:10.1074/jbc.M110.181529.

    Article  CAS  PubMed  Google Scholar 

  • Dingar D, Benoit MJ, Mamarbachi AM, Villeneuve LR, Gillis MA, Grandy S, et al. Characterization of the expression and regulation of MK5 in the murine ventricular myocardium. Cell Signal. 2010;22:1063–75. doi:10.1016/j.cellsig.2010.02.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dwyer SF, Gelman IH. Cross-phosphorylation and interaction between Src/FAK and MAPKAP5/PRAK in early focal adhesions controls cell motility. J Cancer Biol Res. 2014;2(1):1045.

    Google Scholar 

  • Gaestel M. MAPKAP kinases - MKs - two’s company, three’s a crowd. Nat Rev Mol Cell Biol. 2006;7:120–30. doi:10.1038/nrm1834.

    Article  CAS  PubMed  Google Scholar 

  • Gerits N, Mikalsen T, Kostenko S, Shiryaev A, Johannessen M, Moens U. Modulation of F-actin rearrangement by the cyclic AMP/cAMP-dependent protein kinase (PKA) pathway is mediated by MAPK-activated protein kinase 5 and requires PKA-induced nuclear export of MK5. J Biol Chem. 2007a;282:37232–43. doi:10.1074/jbc.M704873200.

    Article  CAS  PubMed  Google Scholar 

  • Gerits N, Van Belle W, Moens U. Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity. Behav Brain Funct. 2007b;3:58. doi:10.1186/1744-9081-3-58.

    Article  PubMed  PubMed Central  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;281:35511–9. doi:10.1074/jbc.M606693200.

    Article  CAS  PubMed  Google Scholar 

  • Kostenko S, Jensen KL, Moens U. Phosphorylation of heat shock protein 40 (Hsp40/DnaJB1) by mitogen-activated protein kinase-activated protein kinase 5 (MK5/PRAK). Int J Biochem Cell Biol. 2014;47:29–37. doi:10.1016/j.biocel.2013.11.004.

    Article  CAS  PubMed  Google Scholar 

  • Kostenko S, Shiryaev A, Gerits N, Dumitriu G, Klenow H, Johannessen M, et al. Serine residue 115 of MAPK-activated protein kinase MK5 is crucial for its PKA-regulated nuclear export and biological function. Cell Mol Life Sci. 2011;68:847–62. doi:10.1007/s00018-010-0496-2.

    Article  CAS  PubMed  Google Scholar 

  • Kress TR, Cannell IG, Brenkman AB, Samans B, Gaestel M, Roepman P, et al. The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis. Mol Cell. 2011;41:445–57. doi:10.1016/j.molcel.2011.01.023.

    Article  CAS  PubMed  Google Scholar 

  • New L, Jiang Y, Zhao M, Liu K, Zhu W, Flood LJ, et al. PRAK, a novel protein kinase regulated by the p38 MAP kinase. EMBO J. 1998;17:3372–84. doi:10.1093/emboj/17.12.3372.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ni H, Wang XS, Diener K, Yao Z. MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated protein kinase, is a substrate of the extracellular-regulated kinase (ERK) and p38 kinase. Biochem Biophys Res Commun. 1998;243:492–6. doi:10.1006/bbrc.1998.8135.

    Article  CAS  PubMed  Google Scholar 

  • Ronkina N, Johansen C, Bohlmann L, Lafera J, Menon MB, Tiedje C, et al. Comparative analysis of two gene-targeting approaches challenges the tumor-suppressive role of the protein kinase MK5/PRAK. PLoS One. 2015;10:e0136138. doi:10.1371/journal.pone.0136138.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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. doi:10.1038/sj.emboj.7600467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seternes OM, Johansen B, Hegge B, Johannessen M, Keyse SM, Moens U. Both binding and activation of p38 mitogen-activated protein kinase (MAPK) play essential roles in regulation of the nucleocytoplasmic distribution of MAPK-activated protein kinase 5 by cellular stress. Mol Cell Biol. 2002;22:6931–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seternes OM, 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. doi:10.1038/sj.emboj.7600489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi Y, Kotlyarov A, Laabeta K, Gruber AD, Butt E, Marcus K, et al. Elimination of protein kinase MK5/PRAK activity by targeted homologous recombination. Mol Cell Biol. 2003;23:7732–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shiryaev A, Kostenko S, Dumitriu G, Moens U. Septin 8 is an interaction partner and in vitro substrate of MK5. World J Biol Chem. 2012;3:98–109. doi:10.4331/wjbc.v3.i5.98.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, et al. PRAK is essential for ras-induced senescence and tumor suppression. Cell. 2007;128:295–308. doi:10.1016/j.cell.2006.11.050.

    Article  CAS  PubMed  Google Scholar 

  • Tak H, Jang E, Kim SB, Park J, Suk J, Yoon YS, et al. 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007;19:2379–87. doi:10.1016/j.cellsig.2007.07.016.

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Liu J, Li X, Zhong Y, Zhong T, Liu Y, et al. PRAK interacts with DJ-1 and prevents oxidative stress-induced cell death. Oxidative Med Cell Longev. 2014;2014:735618. doi:10.1155/2014/735618.

    Google Scholar 

  • Toska K, Kleppe R, Armstrong CG, Morrice NA, Cohen P, Haavik J. Regulation of tyrosine hydroxylase by stress-activated protein kinases. J Neurochem. 2002;83:775–83.

    Article  CAS  PubMed  Google Scholar 

  • Yi T, Zhai B, Yu Y, Kiyotsugu Y, Raschle T, Etzkorn M, et al. Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci USA. 2014;111:E2182–90. doi:10.1073/pnas.1404943111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng H, Seit-Nebi A, Han X, Aslanian A, Tat J, Liao R, et al. A posttranslational modification cascade involving p38, Tip60, and PRAK mediates oncogene-induced senescence. Mol Cell. 2013;50:699–710. doi:10.1016/j.molcel.2013.04.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng M, Wang YH, Wu XN, Wu SQ, Lu BJ, Dong MQ, et al. Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nat Cell Biol. 2011;13:263–72. doi:10.1038/ncb2168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Physiological Chemistry, Hannover Medical School (MHH), Carl-Neuberg str-1, 30625, Hannover, Germany

    Manoj B. Menon & Alexey Kotlyarov

Authors
  1. Manoj B. Menon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexey Kotlyarov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manoj B. Menon .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Menon, M.B., Kotlyarov, A. (2016). MAP Kinase-Activated Protein Kinase 5 (MK5). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_321-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_321-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation