...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The FEBS journal >The anti-inflammatory compound BAY-11-7082 is a potent inhibitor of protein tyrosine phosphatases
【24h】

The anti-inflammatory compound BAY-11-7082 is a potent inhibitor of protein tyrosine phosphatases

机译：抗炎化合物BAY-11-7082是一种有效的蛋白酪氨酸磷酸酶抑制剂

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The families of protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) function in a coordinated manner to regulate signal transduction events that are critical for cellular homeostasis. Aberrant tyrosine phosphorylation, resulting from disruption of either PTP or PTK function, has been shown to be the cause of major human diseases, including cancer and diabetes. Consequently, the characterization of small-molecule inhibitors of these kinases and phosphatases may not only provide molecular probes with which to define the significance of particular signaling events, but also may have therapeutic implications. BAY-11-7082 is an anti-inflammatory compound that has been reported to inhibit IkB kinase activity. The compound has an alpha, beta-unsaturated electrophilic center, which confers the property of being a Michael acceptor; this suggests that it may react with nucleophilic cysteine-containing proteins, such as PTPs. In this study, we demonstrated that BAY-11-7082 was a potent, irreversible inhibitor of PTPs. Using mass spectrometry, we have shown that BAY-11-7082 inactivated PTPs by forming a covalent adduct with the active-site cysteine. Administration of the compound caused an increase in protein tyrosine phosphorylation in RAW 264 macrophages, similar to the effects of the generic PTP inhibitor sodium orthovanadate. These data illustrate that BAY-11-7082 is an effective pan-PTP inhibitor with cell permeability, revealing its potential as a new probe for chemical biology approaches to the study of PTP function. Furthermore, the data suggest that inhibition of PTP function may contribute to the many biological effects of BAY-11-7082 that have been reported to date.
机译：蛋白质酪氨酸磷酸酶（PTP）和蛋白质酪氨酸激酶（PTK）家族以协调的方式发挥功能，调节对细胞稳态至关重要的信号转导事件。由PTP或PTK功能的破坏引起的异常酪氨酸磷酸化已被证明是人类主要疾病的病因，包括癌症和糖尿病。因此，这些激酶和磷酸酶的小分子抑制剂的表征不仅可以提供分子探针来定义特定信号转导事件的重要性，而且可能具有治疗意义。 BAY-11-7082是一种抗炎化合物，据报道可抑制IkB激酶活性。该化合物具有一个α，β-不饱和亲电中心，具有迈克尔受体的特性。这表明它可能与含有亲核半胱氨酸的蛋白质（如PTP）反应。在这项研究中，我们证明了BAY-11-7082是有效的，不可逆的PTP抑制剂。使用质谱法，我们已经显示BAY-11-7082通过与活性位点半胱氨酸形成共价加合物来使PTP失活。化合物的施用导致RAW 264巨噬细胞中蛋白质酪氨酸磷酸化的增加，类似于通用PTP抑制剂原钒酸钠的作用。这些数据说明，BAY-11-7082是一种具有细胞通透性的有效pan-PTP抑制剂，显示出其作为化学生物学方法研究PTP功能的新探针的潜力。此外，数据表明对PTP功能的抑制可能有助于迄今已报道的BAY-11-7082的许多生物学效应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号