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: In order to provide further characterization and assess the phenotypic impact of mutations resulting in genesis and destruction of phosphorylation respectively, we performed siRNA-based knockdown experiments of both TANC1 and RAB11FIP1 across the five cell lines. While knockdown effect could certainly be attributable to many other factors besides these specific mutations, surprisingly, as shown in Figure S3 and detailed in the Supplemental Experimental Procedures, we indeed observed phenotypic effects supporting the most parsimonious expectations arising from ReKINect’s predictions.
Affiliation: Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.