The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors.
This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.
Weinstein-Oppenheimer
C R
CR
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Brody Building of Medical Sciences 5N98C, Greenville, NC 27858, USA.
Blalock
W L
WL
Steelman
L S
LS
Chang
F
F
McCubrey
J A
JA
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D020929:Mitogen-Activated Protein Kinase Kinases / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000494:pharmacology*; D019908:Proto-Oncogene Proteins c-raf / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D018631:ras Proteins / Q000502:physiology
D000970:Antineoplastic Agents; D006133:Growth Substances; D008024:Ligands; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins