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| Spotlight on Molecular Targeted Therapy |
| The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia |
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| J T Lee Jr1 and J A McCubrey1,2 |
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1Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
2Leo Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC, USA
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Correspondence to: J A McCubrey, Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858 USA; Fax: 252 816 3104 |
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| 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. Leukemia (2002) 16, 486-507. DOI: 10.1038/sj/leu/2402460 |
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| Keywords |
| Ras; Raf; MEK; ERK; phosphatase; transcription factor; inhibitors; IL-3; signal transduction; leukemia; oncogenes; PI3K; Akt |
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| Received 21 December 2001; accepted 16 January 2002 |
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| April 2002, Volume 16, Number 4, Pages 486-507 |
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