The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia

Leukemia. 2002 Apr;16(4):486-507. doi: 10.1038/sj.leu.2402460.

Abstract

The Raf/MEK/ERK (MAPK) signal transduction cascade is a vital mediator of a number of cellular fates including growth, proliferation and survival, among others. The focus of this review centers on the MAPK signal transduction pathway, its mechanisms of activation, downstream mediators of signaling, and the transcription factors that ultimately alter gene expression. Furthermore, negative regulators of this cascade, including phosphatases, are discussed with an emphasis placed upon chemotherapeutic intervention at various points along the pathway. In addition, mounting evidence suggests that the PI3K/Akt pathway may play a role in the effects elicited via MAPK signaling; as such, potential interactions and their possible cellular ramifications are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Drug Design
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / enzymology
  • MAP Kinase Kinase Kinase 1*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Signal Transduction / drug effects*
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • ras Proteins