Navigating Human Phosphorylation Networks with the SigNET Suite of On-line Knowledge Bases.

Steven Pelech, Kinexus Bioinformatics Corporation, Vancouver, Canada

The SigNET KnowledgeBank is a suite of open-access knowledgebases with empirical and predictive data on protein expression and phosphorylation, and the interactions of protein kinases with other signalling proteins and protein kinase inhibitors. The PhosphoNET KnowledgeBase (www.phosphonet.ca) provides data on about 200,000 known and another 660,000 predicted human phosphosites, including their evolutionary conservation in 20 other species and prediction of the protein kinases that target these sites. The TranscriptoNET KnowledgeBase documents the mRNA expression levels of 21,000 human genes in 600 human tissues, tumours and cancer cell lines. The DrugKiNET Knowledgebase features data on over 106,000 known kinase drug pair interactions as well as 200,000 predicted kinase drug pairs. These findings are graphically integrated in the KinATLAS website (www.kinatlas.ca) that visualizes predicted and experimentally confirmed interactions between protein kinases and their substrates in a tissue- and cell-specific manner. These websites are being used at Kinexus to guide the creation of hundreds of antibodies and kinase substrate peptides to further map, track and interpret cell signalling networks with microarrays and other antibody-based platforms.