H PYLORI CAGA INHIBITS PAR1-MARK FAMILY KINASES BY MIMICKING HOST SUBSTRATES

H PYLORI CAGA 通过模仿宿主底物抑制 PAR1 标记家族激酶

• 批准号: 8169199
• 负责人: Charles Erec Stebbins
• 金额: $ 0.47万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169199
• 关键词: Computer Retrieval of Information on Scientific Projects Database; Family; Funding; Grant; Helicobacter pylori; Human; Institution; Mutagenesis; Peptides; Phosphotransferases; Protein Kinase Inhibitors; Proteins; Pylorus; Research; Research Personnel; Resources; Risk; Source; Stomach Carcinoma; Structure; United States National Institutes of Health; Virulence; inhibitor/antagonist; protein kinase inhibitor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 幽门螺杆菌的 CagA 蛋白与多种细胞因子相互作用，并与毒力增加和胃癌风险增加相关。我们在此展示了 CagA 子结构域与人激酶 PAR1b/MARK2 的共晶结构，揭示了 CagA 肽模拟该激酶家族的底物，类似于真核蛋白激酶抑制剂。这种相互作用的核心保守残基的诱变使得 CagA 作为 MARK2 抑制剂失去活性