Structure and Dynamic Regulation of Abl Kinases*
Copyright policy )Structure and Dynamic Regulation of Abl Kinases*
The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases. In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton. Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia. Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy. In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity.
- University of Pittsburgh United States
- Northeastern University United States
- Northwestern University United States
Fusion Proteins, bcr-abl, Molecular Conformation, Genes, abl, Models, Biological, Myristic Acid, Proto-Oncogene Mas, Gene Expression Regulation, Enzymologic, Piperazines, Protein Structure, Tertiary, Gene Expression Regulation, Neoplastic, src Homology Domains, Pyrimidines, Models, Chemical, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Benzamides, Mutation, Imatinib Mesylate, Humans, Protein Binding
Fusion Proteins, bcr-abl, Molecular Conformation, Genes, abl, Models, Biological, Myristic Acid, Proto-Oncogene Mas, Gene Expression Regulation, Enzymologic, Piperazines, Protein Structure, Tertiary, Gene Expression Regulation, Neoplastic, src Homology Domains, Pyrimidines, Models, Chemical, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Benzamides, Mutation, Imatinib Mesylate, Humans, Protein Binding
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