Protein kinases are a highly conserved family of proteins that regulate virtually all cellular processes through signaling by phosphorylation, comprising 1.7% of the human genome. Dysregulation often results in aberrant signaling, resulting in diseases such as cancer. In order to better understand the function of the protein kinase family, this research uses a combination of computational and experimental methods to examine regulatory mechanisms in kinases.
One such element of regulation is the use of insertion segments in the kinase domain. While all protein kinases adopt a conserved structural fold, some subfamilies have evolved insertion regions that can allow extra functionality. A well known example is the CMGC family of protein kinases, which contains an insert that aids in substrate recognition near the catalytic site. By identifying and categorizing these insertions, researchers can gain greater insight into kinase regulation. We are developing Kinview as a new framework for bioinformaticians to study conserved residue positions in understudied, or “dark,” kinases using sequence alignments. Once new conserved residues are identified, observation and study of similar mutations allows for predictions about the function of these residue positions in dark kinases. This will aid in better formulation of experimentally testable hypotheses and integrative analyses. Protein kinases and their mutations are often the focus of drug treatments, making it crucial to better understand their sequence variations and the resulting diverse functionality in order to create more effective drug treatments.
