Using protein modification‐based networks to explore cellular signaling and biological function
Jon M. Kornhauser, Sasha L. Tkachev, Bin Zhang, Elźbieta Skrzypek, Beth Murrray, Vaughan M. Latham, Peter V. Hornbeck · The FASEB Journal · 2012
PhosphoSitePlus™ (PSP) is an open proteomics resource that provides manually‐curated information about published sites of protein post‐translational modification (PTMs). Over 100,000 published PTM sites are currently represented in PSP. Several different classes of experimental information about each PTM site are aggregated in PSP, including enzymes (e.g., protein kinases) that are reported to catalyze the modification; ligands and pharmacological agents that modulate the modification; and consequences of a modification, including effects on protein‐protein interactions; effects on the function of the modified protein; and consequences for biological processes, including relevance of the modification to normal and disease states. The rich and extensive data in PSP can be exploited to assemble signaling networks to explore cellular pathways that regulate biological processes including disease. We have used the Cytoscape platform to construct networks representing the data in PSP. Because PSP is unique among proteomic resources in that it contains data that is PTM site‐centric, rather than protein‐centric, analysis of these networks may provide novel insights into cellular signaling. We are employing graphical and statistical approaches, including correlation and cluster analyses, to explore these networks. Our expectation is that the increased resolution of our site‐specific networks, compared to more typical analysis using protein‐centric networks, may allow us to detect novel signaling nodes that are important for specific biological outcomes. www.phosphosite.org