Kinome-wide decoding of network-attacking mutations rewiring cancer signaling.
Bottom Line: However, global analysis of these events is currently limited.Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network rewiring, and the genesis and extinction of phosphorylation sites.We identified and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome.
Affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.Show MeSH
Related in: MedlinePlus
Mentions: Taking the well-characterized case of BRAF V600E, a phospho-mimicking activating mutation, as a positive test case, we confirmed that ReKINect could identify this mutation in one of the ovarian cell lines (ES2) and predict it as kinase activation. We subsequently experimentally confirmed the hyper-phosphorylated state of the BRAF substrate, MEK by immuno-blot in the ES2 line (Figures 6A and 6B).
Affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.