Critical roles of the Raf/MEK/ERK pathway in apoptosis and drug resistance

James A. McCubrey, Fred E. Bertrand, Linda S. Steelman, Fumin Chang, David M. Terrian, Richard A. Franklin

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The Ras/Raf/MEK/ERK pathway plays a critical role in the transmission of signals from growth factor receptors to the nucleus to regulate gene expression. Components of this pathway (e.g., Ras and B-Raf) are frequently mutated in human cancer. Mutations at upstream receptors (e.g., epidermal growth factor receptor [EGFR] and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL), which transmit their signals through the Ras/Raf/MEK/ERK cascade were also frequently observed in human cancer. This pathway also interacts with other signaling pathways (e.g., PI3K/PTEN/Akt) to regulate cell growth. In some cells, mutation of PTEN may contribute to suppression of Raf/MEK/ERK because of the ability of Akt to phosphorylate and inactivate Raf-1. Other regulatory components of the Raf/MEK/ERK pathway (e.g., the Raf Kinase Inhibitor Protein, RKIP) may display altered expression during metastasis, which lead to activation of the pathway. This chapter describes the roles of the Raf/MEK/ERK pathway in signal transduction, prevention of apoptosis and induction of drug resistance.

Original languageEnglish (US)
Title of host publicationApoptosis, Cell Signaling, and Human Diseases
PublisherHumana Press
Pages101-134
Number of pages34
Volume2
ISBN (Print)1588296776, 9781588296771
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

Keywords

  • MAPK
  • Raf
  • apoptosis
  • cell cycle
  • drug resistance
  • signal transduction

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    McCubrey, J. A., Bertrand, F. E., Steelman, L. S., Chang, F., Terrian, D. M., & Franklin, R. A. (2007). Critical roles of the Raf/MEK/ERK pathway in apoptosis and drug resistance. In Apoptosis, Cell Signaling, and Human Diseases (Vol. 2, pp. 101-134). Humana Press. https://doi.org/10.1007/978-1-59745-199-4_5