Proteomic analysis of kinase inhibitor selectivity and function.
Small molecule inhibitors of protein kinases have become highly popular tools in signal transduction research, despite the fact that rather limited data about their respective selectivities have been available. We established an efficient chemical proteomics method to characterize the cellular targets of the widely used inhibitor SB 203580, which was deemed to be rather specific for p38 kinase. Our results revealed several protein kinases as high affinity targets of SB 203580 and therefore imply a far more complicated cellular mode of action of this inhibitor than previously assumed. This raises the important question whether a lack of selectivity is inherent to many other "specific" inhibitors of protein kinases and warrants their evaluation employing experimental approaches adapted from our described proteomic technique.
Godl
Klaus
K
Axxima Pharmaceuticals AG, Max-Lebsche-Platz 32, München, Germany.
Daub
Henrik
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002846:Chromatography, Affinity; D004330:Drosophila; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D020543:Proteome; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D020543:Proteome; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580