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


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
Number of pages34
ISBN (Print)1588296776, 9781588296771
StatePublished - Dec 1 2007
Externally publishedYes


  • 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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