Article
Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF.
Cell - 19 Mar 2004
Wan Paul T C, Garnett Mathew J, Roe S Mark, Lee Sharlene, Niculescu-Duvaz Dan, Good Valerie M, Jones C Michael, Marshall Christopher J, Springer Caroline J, Barford David, Marais Richard
Abstract excerpt
Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase activity and signal to ERK in vivo. Surprisingly, three mutants have reduced kinase activity towards MEK in vitro but, by activating C-RAF in vivo, signal to ERK in cells. The structures of wild...
Topics
- Allosteric Regulation
- Animals
- Catalytic Domain
- Cell Transformation, Neoplastic
- Enzyme Inhibitors
- Gene Expression Regulation, Enzymologic
- MAP Kinase Kinase 1
- MAP Kinase Signaling System
- Mice
- Mitogen-Activated Protein Kinase Kinases
- Mitogen-Activated Protein Kinases
- Models, Molecular