BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo
BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo
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DOI：
10.1074/jbc.m414221200
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发表时间：
2005-05-20
影响因子：
4.8
通讯作者：
Cuenda, A
中科院分区：
文献类型：
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作者：
Kuma, Y;Sabio, G;Cuenda, A
化合物BIRB 796抑制应激活化蛋白激酶p38 α和p38 β，并正在进行治疗炎症性疾病的临床试验。在这里，我们报告说，BIRB 796也抑制活性和激活的SAPK 3/p38 γ。这发生在比抑制p38 α和p38 α的BIRB 796浓度更高的BIRB 796浓度和比抑制JNK同种型活化的BIRB 796浓度更低的BIRB 796浓度下。我们还表明，在这些浓度下，BIRB 796阻断了应力诱导的支架蛋白SAP 97的磷酸化，进一步确定了这是SAPK 3/p38 γ的生理底物。我们的研究结果表明，BIRB 796与SB 203580（一种抑制p38 α和p38 β但不抑制其他p38亚型的化合物）组合，可用于鉴定SAPK 3/p38 γ以及p38 α和p38 β的生理底物。
The compound BIRB796 inhibits the stress-activated protein kinases p38 alpha and p38 beta and is undergoing clinical trials for the treatment of inflammatory diseases. Here we report that BIRB796 also inhibits the activity and the activation of SAPK3/p38 gamma. This occurs at higher concentrations of BIRB796 than those that inhibit p38 alpha and p38 alpha and at lower concentrations than those that inhibit the activation of JNK isoforms. We also show that at these concentrations, BIRB796 blocks the stress-induced phosphorylation of the scaffold protein SAP97, further establishing that this is a physiological substrate of SAPK3/p38 gamma. Our results demonstrate that BIRB796, in combination with SB203580, a compound that inhibits p38 alpha and p38 beta, but not the other p38 isoforms, can be used to identify physiological substrates of SAPK3/p38 gamma as well as those of p38 alpha and p38 beta.