In situ kinase profiling reveals functionally relevant properties of native kinases.
In situ kinase profiling reveals functionally relevant properties of native kinases.
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DOI：
10.1016/j.chembiol.2011.04.011
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发表时间：
2011-06-24
影响因子：
--
通讯作者：
Kozarich JW
中科院分区：
文献类型：
--
作者：
Patricelli MP;Nomanbhoy TK;Wu J;Brown H;Zhou D;Zhang J;Jagannathan S;Aban A;Okerberg E;Herring C;Nordin B;Weissig H;Yang Q;Lee JD;Gray NS;Kozarich JW
蛋白激酶是细胞信号传导的介质，但关于它们的调节和体内特性仍存在重要问题。在这里，我们使用基于探针的化学蛋白质组学平台来分析几种经过充分研究的激酶抑制剂对天然细胞蛋白质组中200多种激酶的作用，并揭示其中一些抑制剂的新生物靶点。在天然和重组激酶抑制谱之间，特别是对于Raf激酶，鉴定了几个显著的差异。本文所示的天然激酶结合谱密切反映了这些抑制剂的细胞活性，即使抑制谱与重组试验结果存在显著差异。此外，Raf激活事件可以在用抑制剂处理活细胞后检测到。这些研究强调了细胞环境中蛋白激酶行为的复杂性，并证明仅用重组/纯化酶进行分析可能会产生误导。
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.
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影响因子：
64.5
作者：
Heidorn SJ;Milagre C;Whittaker S;Nourry A;Niculescu-Duvas I;Dhomen N;Hussain J;Reis-Filho JS;Springer CJ;Pritchard C;Marais R
通讯作者：
Marais R
影响因子：
16
作者：
Karreth, Florian A.;DeNicola, Gina M.;Tuveson, David A.
通讯作者：
Tuveson, David A.
DOI：
10.1073/pnas.0501205102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Okerberg, ES;Wu, JY;Patricelli, MP
通讯作者：
Patricelli, MP
影响因子：
11.5
作者：
Gendreau, Steven B.;Ventura, Richard;Joly, Alison H.
通讯作者：
Joly, Alison H.
影响因子：
14.8
作者：
Liu, Y;Gray, NS
通讯作者：
Gray, NS