Differential Expression Measurements of Phosphoproteome

磷酸化蛋白质组的差异表达测量

• 批准号: 6735810
• 负责人: CHRISTOPHER H BECKER
• 金额: $ 13.2万
• 依托单位: SURROMED, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6735810
• 关键词: affinity chromatography; antibody; biological signal transduction; cell line; clinical research; endopeptidases; high performance liquid chromatography; human tissue; ions; liquid chromatography mass spectrometry; method development; phosphopeptides; phosphoproteins; phosphorylation; protein sequence; protein structure function; serine; threonine; trypsin; tyrosine

DESCRIPTION (provided by applicant): Protein kinases are important regulators of intracellular signal-transduction pathways mediating cellular growth and development. The defining feature of malignant neoplasms is their deregulated cell growth. Understanding the underlying phosphoproteome in normal and tumor tissue together with an understanding of the effect of targeted anti-protein kinase therapies is essential for advancing this important therapeutic approach. Because protein phosphorylation and dephosphorylation play a critical role in biology generally, and in cancer in particular, a tool that sensitively and quantitatively monitors many phosphorylated proteins and their site(s) of phosphorylation is of medical and commercial value. It also would be desirable to perform such measurements in a discovery-based mode, not limiting the investigation to only previously identified proteins or phosphorylation sites. Current tools to elucidate the phosphoproteome are limited. SurroMed proposes a major advance in quantitative differential expression measurements of phosphorylated proteins in a discovery context. SurroMed recently has developed a state-of-the-art mass spectrometry-based quantitative differential expression measurement system that is applicable to large numbers of clinical samples. However, this method is not currently selective for phosphoproteins and therefore sensitivity and dynamic range for phosphoproteins is limited. The proposed new technological development will allow for highly selective capture of phosphorylated proteins in a way that will be readily coupled to SurroMed's existing differential expression measurement system. These combined technologies will then provide a sensitive and quantitative differential expression measurement system for phosphoproteins, able to track and discover many phosphoproteins and identify their sites of phosphorylation.

描述（由申请人提供）： 蛋白激酶是介导细胞生长和发育的细胞内信号转导途径的重要调节剂。恶性肿瘤的显着特征是细胞生长失调。了解正常和肿瘤组织中潜在的磷酸化蛋白质组以及了解靶向抗蛋白激酶疗法的效果对于推进这一重要的治疗方法至关重要。 由于蛋白质磷酸化和去磷酸化通常在生物学中，特别是在癌症中发挥关键作用，因此灵敏且定量地监测许多磷酸化蛋白质及其磷酸化位点的工具具有医学和商业价值。还希望以基于发现的模式进行此类测量，而不是将研究限制于仅先前鉴定的蛋白质或磷酸化位点。 目前阐明磷酸化蛋白质组的工具是有限的。 SurroMed 提出了在发现环境中磷酸化蛋白质的定量差异表达测量方面的重大进展。 SurroMed 最近开发了一种最先进的基于质谱的定量差异表达测量系统，适用于大量临床样本。然而，该方法目前对磷蛋白没有选择性，因此磷蛋白的灵敏度和动态范围有限。拟议的新技术开发将允许以一种易于与 SurroMed 现有的差异表达测量系统耦合的方式高度选择性地捕获磷酸化蛋白质。这些组合技术将为磷蛋白提供灵敏的定量差异表达测量系统，能够跟踪和发现许多磷蛋白并识别其磷酸化位点。