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.
