HEAT SHOCK PROTEIN HSP-90 FOLLOWING INJURY

受伤后的热休克蛋白 HSP-90

• 批准号: 6078019
• 负责人: MICHAEL B YAFFE
• 金额: $ 11.58万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078019
• 关键词: biological signal transduction; chemical binding; enzyme structure; histopathology; intermolecular interaction; molecular chaperones; molecular pathology; protein kinase; protein structure function; stress proteins; tissue /cell culture

DESCRIPTION (Adapted from the applicant's abstract) The regulation of signal transduction events following tissue injury is of prime importance in maintaining cell viability. This process is particularly relevant to diseases of the respiratory and cardiovascular system, where tissue insults such as ischemia, reperfusion, and sepsis are common. The applicants propose that this occurs through the involvement of the 90-kDa heat-shock protein hsp9O. Hsp9O is an abundant and ubiquitously distributed stress protein present in all living organisms from bacteria to man. Although hsp9O plays a role in steroid receptor maturation, and forms stable associations with several protein kinases, no clear picture regarding hsp9O's exact function at the molecular level has emerged. In this proposal, they hypothesize that hsp9O functions as a protein kinase chaperone, assisting in the correct packing of the regulatory and catalytic domains. By sequestering the catalytic subunits of a variety of protein kinases following injury, hsp9O could prevent both non-specific kinase denaturation/aggregation and the inappropriate activation of signal transduction pathways. In vivo cell culture experiments will be used to determine the identity and activity of protein kinases that interact with hsp9O following injury. In vitro protein biochemistry experiments will examine which kinase subfamilies contain members capable of interacting with hsp9O, and elucidate whether hsp9O plays a chaperone-like function in this interaction. Finally the mechanism of hsp9O kinase binding and release will be investigated using kinase mutants, domain- and loop-swapping constructs, and oriented peptide libraries, based on extrapolations from known protein kinase crystal structures.

描述 （改编自申请人的摘要）信号的规定 组织损伤后的转导事件至关重要 维持细胞活力。 这个过程特别适用于 呼吸系统和心血管系统疾病，其中组织受到损害 例如缺血、再灌注和败血症是常见的。 申请人 认为这是通过 90 kDa 热激的参与而发生的 蛋白质 hsp9O。 Hsp9O 是一种丰富且普遍分布的应激 蛋白质存在于从细菌到人类的所有生物体中。 虽然 hsp9O 在类固醇受体成熟中发挥作用，并形成稳定的 与几种蛋白激酶的关联，没有明确的图片 hsp9O 在分子水平上的确切功能已经显现。 在这个 提议，他们假设 hsp9O 充当蛋白激酶 伴侣，协助调节和催化的正确包装 域。 通过隔离多种蛋白质的催化亚基 损伤后的激酶，hsp9O 可以预防非特异性激酶 变性/聚集和信号的不当激活 转导途径。 体内细胞培养实验将用于确定身份和 损伤后与 hsp9O 相互作用的蛋白激酶的活性。 在 体外蛋白质生物化学实验将检查哪些激酶亚家族 包含能够与 hsp9O 相互作用的成员，并阐明是否 hsp9O 在此相互作用中发挥类似伴侣的功能。 最后 hsp9O 激酶结合和释放的机制将使用以下方法进行研究 激酶突变体、结构域和环交换结构以及定向肽 文库，基于已知蛋白激酶晶体的推断 结构。

项目成果

Priming of the neutrophil respiratory burst is species-dependent and involves MAP kinase activation.

中性粒细胞呼吸爆发的启动具有物种依赖性，并且涉及 MAP 激酶激活。

• 发表时间: 1999
• 期刊: Surgery
• 影响因子: 3.8
• 作者: Yaffe,MB;Xu,J;Burke,PA;Forse,RA;Brown,GE
• 通讯作者: Brown,GE