Article
Autoinhibition of Bcr-Abl through its SH3 domain.
Molecular cell - 1 Jul 2003
Smith Kristen M, Yacobi Rinat, Van Etten Richard A
Abstract excerpt
Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt oligomerization, but restored by an SH3 point mutation that blocks ligand binding or a...
Topics
- 3T3 Cells
- Alanine
- Amino Acid Sequence
- Animals
- Binding Sites
- Catalytic Domain
- Cell Transformation, Neoplastic
- Enzyme Inhibitors
- Eukaryotic Cells
- Feedback, Physiological
- Fusion Proteins, bcr-abl
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Mice
- Mice, Inbred BALB C
- Models, Molecular
- Mutation
- Phosphorylation