Quantifying oncogenic phosphotyrosine signaling networks through systems biology.
Pathways linking oncogenic mutations to increased proliferative or migratory capacity are poorly characterized, yet provide potential targets for therapeutic intervention. As tyrosine phosphorylation signaling networks are known to mediate proliferation and migration, and frequently go awry in cancers, a comprehensive understanding of these networks in normal and diseased states is warranted. To this end, recent advances in mass spectrometry, protein microarrays, and computational algorithms provide insight into various aspects of the network including phosphotyrosine identification, analysis of kinase/phosphatase substrates, and phosphorylation-mediated protein-protein interactions. Here we detail technological advances underlying these system-level approaches and give examples of their applications. By combining multiple approaches, it is now possible to quantify changes in the phosphotyrosine signaling network with various oncogenic mutations, thereby unveiling novel therapeutic targets.
Del Rosario
Amanda M
AM
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
White
Forest M
FM
D013058:Mass Spectrometry; D046228:Microarray Analysis; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D015398:Signal Transduction; D049490:Systems Biology
D019000:Phosphotyrosine