A Bcr/Abl Kinase Antagonist for Chronic Myelogenous Leukemia: a Promising Path for Progress Emerges

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Abstract
Protein kinases catalyze the transfer of the γ-phosphate of adenosine triphosphate (ATP) to protein acceptors. Over the past 40 years, we have learned that protein phosphorylation is a central regulatory strategy to alter cellular function. Proteins can be phosphorylated on serine, threonine, tyrosine, and rarely histidine residues. However, tyrosine kinases have come to be understood as critical regulators of cell proliferation, invasion, metastasis, and cell survival. Tyrosine kinases exist as two major classes. In receptor tyrosine kinases, including platelet-derived growth factor receptor, epidermal growth factor receptor, and its homologue the c-erbB2 oncogene product, the kinase activity is actually part of the receptor, which has one extracellular domain to bind molecules promoting proliferation at the cell surface, a second domain that traverses the cell membrane, and an intracellular catalytic domain that acts to cause tyrosine phosphorylation. Nonreceptor tyrosine kinases exist in the cytoplasm, but they can be recruited to distinct subcellular locations after receipt of various cellular signals. Tyrosine kinases phosphorylate proteins that change cell function, either by directly activating or inhibiting “downstream” kinases, or by creating tyrosine phosphates that serve as “scaffold” sites for the assembly of regulatory molecules ( 1 ).