Differential Expression Measurements of Phosphoproteome

描述(由申请人提供)： 蛋白激酶是调节细胞生长发育的细胞内信号转导通路的重要调节者。恶性肿瘤的定义特征是其细胞生长不受控制。了解正常组织和肿瘤组织中潜在的磷酸蛋白质组，以及了解靶向抗蛋白激酶治疗的效果，对于推进这一重要的治疗方法至关重要。 由于蛋白质的磷酸化和去磷酸化在生物学中起着至关重要的作用，特别是在癌症中，灵敏和定量地监测许多磷酸化的蛋白质及其磷酸化位点(S)的工具具有医疗和商业价值。还希望以基于发现的模式进行这种测量，而不是仅将研究局限于先前已确定的蛋白质或磷酸化位点。 目前用于阐明磷酸蛋白质组的工具有限。SurroMed提出了一项重大进展，即在发现背景下对磷酸化蛋白质的定量差异表达进行测量。 SurroMed最近开发了一种最先进的基于质谱学的定量差异表达测量系统，适用于大量临床样本。然而，这种方法目前对磷蛋白没有选择性，因此对磷蛋白的灵敏度和动态范围是有限的。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相结合的方式高度选择性地捕获磷酸化蛋白质。这些结合的技术将为磷蛋白提供一个灵敏和定量的差异表达测量系统，能够跟踪和发现许多磷蛋白并确定它们的磷酸化位置。

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.