Skip to main content

Mek

  • Reference work entry
  • First Online:
  • 65 Accesses

Synonyms

MAP2K1/2; MAPK kinase 1/2 (MAPKK1/2); Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinases 1/2 (MEK1/2); MKK1/2; p45MAPKK; PRKMK1/2

Historical Background

The transmission of extracellular signals to their intracellular targets is mediated by a network of interacting proteins that governs a large number of cellular processes including proliferation, differentiation, stress response, and apoptosis. One of the central components in the transmission network is the ERK cascade, which is composed of sequential phosphorylation and activation of the protein kinases Raf, MEK, ERK, and MAPKAPKs. In turn, the latter two components of the cascade phosphorylate a large number of regulatory proteins, culminating in the induction and regulation of proper downstream cellular processes. This cascade was identified in the late 1980s and early 1990s of the previous century by several research groups that studied growth factor receptor signaling. At that...

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Ahn NG, Seger R, Bratlien RL, Diltz CD, Tonks NK, Krebs EG. Multiple components in an epidermal growth factor-stimulated protein kinase cascade. In vitro activation of myelin basic protein/microtubule-associated protein-2 kinase. J Biol Chem. 1991;266:4220–7.

    CAS  PubMed  Google Scholar 

  • Bendetz-Nezer S, Seger R. Full molecular page of MEK1. AfCS/Nature SignalGateway. 2005; https://doi.org/10.1038/mp.a001505.01.

    Article  Google Scholar 

  • Burgermeister E, Seger R. MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma. Cell Cycle. 2007;6:1539–48.

    Article  CAS  PubMed  Google Scholar 

  • Catalanotti F, Reyes G, Jesenberger V, Galabova-Kovacs G, et al. A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal. Nat Struct Mol Biol. 2009;16:294–303.

    Article  CAS  PubMed  Google Scholar 

  • Chuderland D, Konson A, Seger R. Identification and characterization of a general nuclear translocation signal in signaling proteins. Mol Cell. 2008;31:850–61.

    Article  CAS  PubMed  Google Scholar 

  • Fukuda M, Gotoh I, Adachi M, Gotoh Y, Nishida E. A novel regulatory mechanism in the mitogen-activated protein (MAP) kinase cascade. Role of nuclear export signal of MAP kinase kinase. J Biol Chem. 1997;272:32642–8.

    Article  CAS  PubMed  Google Scholar 

  • Gomez N, Cohen P. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature. 1991;353:170–3.

    Article  CAS  PubMed  Google Scholar 

  • Kyriakis JM, App H, Zhang FX, Banerjee P, Brautigan DL, et al. Raf-1 activates MAP kinase–kinase. Nature. 1992;358:417–21.

    Article  CAS  PubMed  Google Scholar 

  • Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, et al. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat Struct Mol Biol. 2004;11:1192–7.

    Article  CAS  PubMed  Google Scholar 

  • Perry RL, Parker MH, Rudnicki MA. Activated MEK1 binds the nuclear MyoD transcriptional complex to repress transactivation. Mol Cell. 2001;8:291–301.

    Article  CAS  PubMed  Google Scholar 

  • Rubinfeld H, Hanoch T, Seger R. Identification of a cytoplasmic-retention sequence in ERK2. J Biol Chem. 1999;274:30349–52.

    Article  CAS  PubMed  Google Scholar 

  • Sebolt-Leopold JS, Dudley DT, Herrera R, Van Becelaere K, Wiland A, et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999;5:810–6.

    Article  PubMed  CAS  Google Scholar 

  • Seger R, Krebs EG. The MAPK signaling cascade. FASEB J. 1995;9:726–35.

    Article  CAS  PubMed  Google Scholar 

  • Shaul YD, Gibor G, Plotnikov A, Seger R. Specific phosphorylation and activation of ERK1c by MEK1b: a unique route in the ERK cascade. Genes Dev. 2009;23:1779–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Takekawa M, Tatebayashi K, Saito H. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. Mol Cell. 2005;18:295–306.

    Article  CAS  PubMed  Google Scholar 

  • Tanoue T, Adachi M, Moriguchi T, Nishida E. A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol. 2000;2:110–6.

    Article  CAS  PubMed  Google Scholar 

  • Yao Z, Seger R. The ERK signaling cascade–views from different subcellular compartments. Biofactors. 2009;35:407–16.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the Israel Science Foundation. RS is an incumbent of the Yale S. Lewine and Ella Miller Lewine professorial chair for cancer research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rony Seger .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Procaccia, S., Seger, R. (2018). Mek. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_424

Download citation

Publish with us

Policies and ethics