Abstract by Jacob Owen
Chemistry and Biochemistry
Characterization of TNK2 activation through regulation of the UBA domain
Tyrosine kinase non-receptor 2 (TNK2) is a member of the ACK family of tyrosine kinases that is overexpressed in many cancer types including lung, breast, gastrointestinal, prostate, and kidney. Overexpression of TNK2 has been correlated with poor patient outcomes. However, the mechanism by which TNK2 is activated and regulated is not well studied. TNK2 along with the other member of the ACK family, TNK1, are unique among kinases in that they possess a functional ubiquitin associated (UBA) domain at their C termini. Our preliminary data from studies on TNK1 support the hypothesis that the UBA domain binds multiple poly-ubqiuitin linkages and is required for ACK kinase Activity. We are currently testing this hypothesis by generating ubiquitin binding-deficient mutants of TNK2 and measuring their ability to transform cells in culture.