Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Mitogen-Activated Protein Kinases

  • Sylvain MelocheEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_193


Historical Background

Mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that play a key role in transducing chemical and physical extracellular signals into a variety of intracellular responses. These protein kinases are among the most highly studied signaling molecules, as reflected by the more than 97,000 papers on “MAP kinase” listed in PubMed as of August 2016. This chapter provides a broad overview of the different subfamilies of MAP kinases. Each subfamily will then be treated in more detail in individual chapters of this encyclopedia.

The discovery of MAP kinases goes back to 1987 when Ray and Sturgill reported the identification of a novel insulin-stimulated serine/threonine kinase activity from extracts of 3T3-L1 adipocytes that was capable of phosphorylating microtubule-associated protein-2 in vitro (Ray and Sturgill 1987). As a result, the enzyme was called microtubule-associated...

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  1. Ahn NG, Seger R, Krebs EG. The mitogen-activated protein kinase activator. Curr Opin Cell Biol. 1992;4:992–9.CrossRefPubMedGoogle Scholar
  2. Anderson NG, Maller JL, Tonks NK, Sturgill TW. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature. 1990;343:651–3.CrossRefPubMedGoogle Scholar
  3. Avruch J. MAP kinase pathways: the first twenty years. Biochim Biophys Acta. 2007;1773:1150–60.CrossRefPubMedGoogle Scholar
  4. Ben-Shachar S, Ou Z, Shaw CA, Belmont JW, Patel MS, Hummel M, Amato S, Tartaglia N, Berg J, Sutton VR, Lalani SR, Chinault AC, Cheung SW, Lupski JR, Patel A. 22q11.2 distal deletion: a recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome. Am J Hum Genet. 2008;82:214–21.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Boulton TG, Yancopoulos GD, Gregory JS, Slaughter C, Moomaw C, Hsu J, Cobb MH. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science. 1990;249:64–7.CrossRefPubMedGoogle Scholar
  6. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75:50–83.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Coulombe P, Meloche S. Atypical mitogen-activated protein kinases: structure, regulation and functions. Biochim Biophys Acta. 2007;1773:1376–87.CrossRefPubMedGoogle Scholar
  8. Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010;1802:396–405.CrossRefPubMedGoogle Scholar
  9. Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012;92:689–737.CrossRefPubMedGoogle Scholar
  10. Lawrence MC, Jivan A, Shao C, Duan L, Goad D, Zaganjor E, Osborne J, McGlynn K, Stippec S, Earnest S, Chen W, Cobb MH. The roles of MAPKs in disease. Cell Res. 2008;18:436–42.CrossRefPubMedGoogle Scholar
  11. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.PubMedGoogle Scholar
  12. Rauen KA. The RASopathies. Annu Rev Genomics Hum Genet. 2013;14:355–69.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Ray LB, Sturgill TW. Rapid stimulation by insulin of a serine/threonine kinase in 3T3-L1 adipocytes that phosphorylates microtubule-associated protein 2 in vitro. Proc Natl Acad Sci USA. 1987;84:1502–6.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Ray LB, Sturgill TW. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Proc Natl Acad Sci USA. 1988;85:3753–7.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Rossomando AJ, Payne DM, Weber MJ, Sturgill TW. Evidence that pp42, a major tyrosine kinase target protein, is a mitogen-activated serine/threonine protein kinase. Proc Natl Acad Sci USA. 1989;86:6940–3.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Samatar AA, Poulikakos PI. Targeting RAS-ERK signaling in cancer: promises and challenges. Nat Rev Drug Discov. 2014;13:928–42.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007;7:295–308.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999;79:143–80.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of Research in Immunology and CancerUniversité de MontréalMontrealCanada
  2. 2.Department of Pharmacology and Molecular Biology ProgramUniversité de MontréalMontrealCanada