Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Extracellular Signal-Regulated Kinases 1 and 2

Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_2070-2

Synonyms

Definition

The extracellular signal-regulated kinases (ERKs) 1 and 2 (also referred to as mitogen-activated protein kinases 1 and 2; MAPK1/2) constitute major regulators of cell proliferation and survival and also regulate motility, differentiation, and senescence. They phosphorylate a multitude of cytoplasmic and nuclear substrates, including transcription factors. Mutations or overexpression of upstream ERK activators are implicated in oncogene-induced signaling in a wide variety of tumors. Inhibitors of ERK activation are used in cancer therapy.

Characteristics

The ERK Activation Cascade

ERKs 1 and 2 are activated through dual phosphorylation by a kinase cascade involving the upstream signaling entities RAS (rat sarcoma proto-oncogene), RAF (rat fibrosarcoma proto-oncogene), and MEK1/2 (MAPK/ERKs 1 and 2) (Fig. 1). There are three forms of RAS, KRAS (Kirsten RAS), HRAS (Harvey...

Keywords

Human Epidermal Growth Factor Receptor Papillary Thyroid Carcinoma Focal Adhesion Kinase BRAF Mutation Serum Response Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Deschênes-Simard X, Kottakis F, Meloche S, Ferbeyre G (2014) ERKs in cancer: friends or foes? Cancer Res 74:412–419CrossRefPubMedGoogle Scholar
  2. Keyse SM (2008) Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev 27:253–261CrossRefPubMedGoogle Scholar
  3. Lito P, Rosen N, Solit DB (2013) Tumor adaptation and resistance to RAF inhibitors. Nat Med 19:1401–1409CrossRefPubMedGoogle Scholar
  4. Mendoza MC, Er EE, Blenis J (2011) The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci 36:320–328PubMedCentralCrossRefPubMedGoogle Scholar
  5. Roskoski R Jr (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66:105–143CrossRefPubMedGoogle Scholar

See Also

  1. (2012) Phorbol ester. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin, p 2865. doi:10.1007/978-3-642-16483-5_4522Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Department of PathologyCopenhagen University HospitalHvidovreDenmark