| Literature DB >> 21700206 |
Matthew P Patricelli1, Tyzoon K Nomanbhoy, Jiangyue Wu, Heidi Brown, David Zhou, Jianming Zhang, Subadhra Jagannathan, Arwin Aban, Eric Okerberg, Chris Herring, Brian Nordin, Helge Weissig, Qingkai Yang, Jiing-Dwan Lee, Nathanael S Gray, John W Kozarich.
Abstract
Protein kinases are intensely studied mediators of cellular signaling, yet important questions remain regarding their regulation and in vivo properties. Here, we use a probe-based chemoprotemics platform to profile several well studied kinase inhibitors against >200 kinases in native cell proteomes and reveal biological targets for some of these inhibitors. Several striking differences were identified between native and recombinant kinase inhibitory profiles, in particular, for the Raf kinases. The native kinase binding profiles presented here closely mirror the cellular activity of these inhibitors, even when the inhibition profiles differ dramatically from recombinant assay results. Additionally, Raf activation events could be detected on live cell treatment with inhibitors. These studies highlight the complexities of protein kinase behavior in the cellular context and demonstrate that profiling with only recombinant/purified enzymes can be misleading.Entities:
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Year: 2011 PMID： 21700206 PMCID： PMC3142620 DOI： 10.1016/j.chembiol.2011.04.011
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521