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Perspectives
Unraveling Kinase Signaling Pathways with Chemical Genetic and Chemical Proteomic Approaches
Emmanuel Beillard and Owen N. Witte
volume 4 | issue 3
march 2005Pages: 434 - 437
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Protein kinases are involved in a wide variety of physiological and pathological processes. Small kinase inhibitor molecules are frequently used to dissect signaling pathways or to counteract oncogenic events. However, in many cases the precise role of a given inhibitor is not well understood. Besides a known primary target, potential secondary targets might be involved in the biological response to the drug. We describe recent advances in chemical genetics and chemical proteomics that allow a new comprehensive analysis of kinase signaling pathways. One approach consists of engineering the kinase pocket to design inhibitor sensitive and resistant alleles. A second strategy is to modify the kinase pocket to specifically accept radio-labeled ATP analogs, allowing the identification of direct downstream substrates after transphosphorylation. The third method takes advantage of recently improved inhibitor affinity chromatography to identify inhibitor targets by mass spectrometry. Ultimately, these new technologies will help define the actions of kinase inhibitors useful for human disease treatment.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.