Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

ERK1/ERK2

Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_470

Synonyms

Historical Background

Several years prior to ERK1 and ERK2 cloning, respectively, in 1990 and 1991 (Boulton et al. 1991), the close correlation between mitogen action and the increased double phosphorylation of two proteins of 41 and 43 kDa on a phosphotyrosine residue and a phosphothreonine/phosphoserine was revealed by two-dimensional polyacrylamide-gel electrophoresis (reviewed in Chambard et al. [2007]). Because of the sustained phosphorylation during the critical part of G0/G1 phase of the cell cycle, these two proteins known as p41 and p43 were suspected of playing a key role in cell cycle entry. Finally ERK1 was purified and cloned as a protein that phosphorylates microtubules-associated protein2 (MAPK2)...

This is a preview of subscription content, log in to check access

References

  1. Boulton TG, Nye SH, Robbins DJ, Ip NY, Radziejewska 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(4):663–75.PubMedCrossRefGoogle Scholar
  2. Burack WR, Shaw AS. Live cell imaging of ERK and MEK: simple binding equilibrium explains the regulated nucleocytoplasmic distribution of ERK. J Biol Chem. 2005;280(5):3832–7.PubMedCrossRefGoogle Scholar
  3. Cagnol S, Chambard JC. ERK and cell death: mechanisms of ERK-induced cell death–apoptosis, autophagy and senescence. FEBS J. 2010;277(1):2–21.PubMedCrossRefGoogle Scholar
  4. Chambard JC, Lefloch R, Pouyssegur J, Lenormand P. ERK implication in cell cycle regulation. Biochim Biophys Acta. 2007;1773(8):1299–310.PubMedCrossRefGoogle Scholar
  5. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. N Engl J Med. 2011 Jun 5. [Epub ahead of print].Google Scholar
  6. Dankort D, Curley DP, Cartlidge RA, Nelson B, Karnezis AN, Damsky Jr WE, et al. Braf(V600E) cooperates with Pten loss to induce metastatic melanoma. Nat Genet. 2009;41(5):544–52.PubMedCrossRefGoogle Scholar
  7. Dhomen N, Reis-Filho JS, da Rocha Dias S, Hayward R, Savage K, Delmas V, et al. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009;15(4):294–303.PubMedCrossRefGoogle Scholar
  8. Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, Copeland TD, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor [see comments]. Science. 1998;280(5364):734–7.PubMedCrossRefGoogle Scholar
  9. Ebisuya M, Kondoh K, Nishida E. The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. J Cell Sci. 2005;118(14):2997–3002.PubMedCrossRefGoogle Scholar
  10. Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science. 2009;324(5929):938–41.PubMedCrossRefGoogle Scholar
  11. Fujioka A, Terai K, Itoh RE, Aoki K, Nakamura T, Kuroda S, et al. Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. J Biol Chem. 2006;281(13):8917–26.PubMedCrossRefGoogle Scholar
  12. Hu S, Xie Z, Onishi A, Yu X, Jiang L, Lin J, et al. Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009;139(3):610–22.PubMedCrossRefGoogle Scholar
  13. Kelleher 3rd RJ, Govindarajan A, Jung HY, Kang H, Tonegawa S. Translational control by MAPK signaling in long-term synaptic plasticity and memory. Cell. 2004;116(3):467–79.PubMedCrossRefGoogle Scholar
  14. Keyse SM. kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev. 2008;27(2):253–61.PubMedCrossRefGoogle Scholar
  15. Kosako H, Yamaguchi N, Aranami C, Ushiyama M, Kose S, Imamoto N, et al. Phosphoproteomics reveals new ERK MAP kinase targets and links ERK to nucleoporin-mediated nuclear transport. Nat Struct Mol Biol. 2009;16(10):1026–35.PubMedCrossRefGoogle Scholar
  16. Lee T, Hoofnagle AN, Kabuyama Y, Stroud J, Min X, Goldsmith EJ, et al. Docking motif interactions in MAP kinases revealed by hydrogen exchange mass spectrometry. Mol Cell. 2004;14(1):43–55.PubMedCrossRefGoogle Scholar
  17. Lee SJ, Pfluger PT, Kim JY, Nogueiras R, Duran A, Pages G, et al. A functional role for the p62-ERK1 axis in the control of energy homeostasis and adipogenesis. EMBO Rep. 2010;11(3):226–32.PubMedCrossRefGoogle Scholar
  18. Lefloch R, Pouyssegur J, Lenormand P. Total ERK1/2 activity regulates cell proliferation. Cell Cycle. 2009;8(5):705–11.PubMedCrossRefGoogle Scholar
  19. Lidke DS, Huang F, Post JN, Rieger B, Wilsbacher J, Thomas JL, et al. ERK nuclear translocation is dimerization-independent but controlled by the rate of phosphorylation. J Biol Chem. 2010;285(5):3092–4102.PubMedCrossRefGoogle Scholar
  20. Murphy LO, Blenis J. MAPK signal specificity: the right place at the right time. Trends Biochem Sci. 2006;31(5):268–75.PubMedCrossRefGoogle Scholar
  21. Pages G, Lenormand P, L'Allemain G, Chambard JC, Meloche S, Pouyssegur J. Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation. Proc Natl Acad Sci U S A 1993;90(18):8319–23.PubMedCrossRefGoogle Scholar
  22. Pratilas CA, Taylor BS, Ye Q, Viale A, Sander C, Solit DB, et al. (V600E)BRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway. Proc Natl Acad Sci USA. 2009;106(11):4519–24.PubMedCrossRefGoogle Scholar
  23. Pullikuth AK, Catling AD. Extracellular signal-regulated kinase promotes Rho-dependent focal adhesion formation by suppressing p190A RhoGAP. Mol Cell Biol. 2010;30(13):3233–48.PubMedCrossRefGoogle Scholar
  24. Samuels IS, Karlo JC, Faruzzi AN, Pickering K, Herrup K, Sweatt JD, et al. Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci. 2008;28(27):6983–95.PubMedCrossRefGoogle Scholar
  25. Srinivasan R, Zabuawala T, Huang H, Zhang J, Gulati P, Fernandez S, et al. Erk1 and Erk2 regulate endothelial cell proliferation and migration during mouse embryonic angiogenesis. PLoS ONE. 2009;4(12):e8283.PubMedCrossRefGoogle Scholar
  26. Torii S, Yamamoto T, Tsuchiya Y, Nishida E. ERK MAP kinase in G cell cycle progression and cancer. Cancer Sci. 2006;97(8):697–702.PubMedCrossRefGoogle Scholar
  27. Voisin L, Saba-El-Leil MK, Julien C, Fremin C, Meloche S. Genetic demonstration of a redundant role of extracellular signal-regulated kinase 1 (ERK1) and ERK2 mitogen-activated protein kinases in promoting fibroblast proliferation. Mol Cell Biol. 2010;30(12):2918–32.PubMedCrossRefGoogle Scholar
  28. Vomastek T, Iwanicki MP, Burack WR, Tiwari D, Kumar D, Parsons JT, et al. Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction. Mol Cell Biol. 2008;28(22):6954–66.PubMedCrossRefGoogle Scholar
  29. von Kriegsheim A, Baiocchi D, Birtwistle M, Sumpton D, Bienvenut W, Morrice N, et al. Cell fate decisions are specified by the dynamic ERK interactome. Nat Cell Biol. 2009;11(12):1458–64.CrossRefGoogle Scholar
  30. Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, Macconaill LE, Hahn WC, Meyerson M, Garraway LA. Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling. J Clin Oncol 2011 Mar 7. [Epub ahead of print].Google Scholar
  31. Watanabe K, Tanimura S, Uchiyama A, Sakamoto T, Kawabata T, Ozaki K, Kohno M. Blockade of the extracellular signal-regulated kinase pathway enhances the therapeutic efficacy of microtubule-destabilizing agents in human tumor xenograft models. Clin Cancer Res 2011;16(4):1170–8.CrossRefGoogle Scholar
  32. Yamamoto T, Ebisuya M, Ashida F, Okamoto K, Yonehara S, Nishida E. Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. Curr Biol. 2006;16(12):1171–82.PubMedCrossRefGoogle Scholar
  33. Yazicioglu MN, Goad DL, Ranganathan A, Whitehurst AW, Goldsmith EJ, Cobb MH. Mutations in ERK2 binding sites affect nuclear entry. J Biol Chem. 2007;282(39):28759–67.PubMedCrossRefGoogle Scholar
  34. Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006;24(1):21–44.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Institute of Developmental Biology and Cancer, CNRS UMR6543Université de NiceNiceFrance