In Situ Kinase Profiling Reveals Functionally Relevant Properties of Native Kinases
| Autor: | Helge Weissig, Nathanael S. Gray, Chris Herring, Arwin Aban, David Zhou, Heidi E. Brown, Eric Okerberg, Subadhra Jagannathan, John W. Kozarich, Qingkai Yang, Jianming Zhang, Jiing Dwan Lee, Tyzoon K. Nomanbhoy, Jiangyue Wu, Brian E. Nordin, Matthew P. Patricelli |
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| Rok vydání: | 2011 |
| Předmět: |
Clinical Biochemistry
Dasatinib MAP Kinase Kinase 5 Mitogen-activated protein kinase kinase Biochemistry Article Adenosine Triphosphate Cell Line Tumor Drug Discovery Humans ASK1 c-Raf Protein Kinase Inhibitors Molecular Biology Pharmacology MAP kinase kinase kinase biology Cyclin-dependent kinase 2 General Medicine Recombinant Proteins Cell biology Thiazoles Pyrimidines Mitogen-activated protein kinase biology.protein Molecular Medicine raf Kinases Cyclin-dependent kinase 9 Kinase binding Protein Kinases Protein Binding |
| Zdroj: | Chemistry & Biology. 18:699-710 |
| ISSN: | 1074-5521 |
| Popis: | 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 more than 200 kinases in native cell proteomes and reveal new 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 upon 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. |
| Databáze: | OpenAIRE |
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