The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia.
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.
Lee
J T
JT
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA.
McCubrey
J A
JA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology; D048728:MAP Kinase Kinase Kinase 1; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D018631:ras Proteins