A Partial Characterization of Novel PFTAIRE Protein Kinase 2, Poster 42

Cyclin dependent kinases (CDKs) and cyclins form heterodimers that coordinate various events throughout the cell cycle. Consequently, CDKs can act as potential therapeutic targets in proliferative diseases, such as cancer.... [ view full abstract ]

Cyclin dependent kinases (CDKs) and cyclins form heterodimers that coordinate various events throughout the cell cycle. Consequently, CDKs can act as potential therapeutic targets in proliferative diseases, such as cancer. Here, we partially characterized a novel cyclin dependent kinase, PFTAIRE protein kinase 2 (PFTK2). PFTK2 localizes to the kinetochores during mitosis and co-localizes with Aurora B in the presence of taxol, an anti-cancer chemotherapy drug. Since Aurora B plays a key regulatory role during mitosis, its co-localization with PFTK2 in the presence of an anti-mitotic alludes to PFTK2’s importance in regulation of the cell cycle. In this work, we construct PFTK2 point mutants with alanine/glycine substitutions at predicted post-translational modification sites to determine which residues may be critical for PFTK2’S localization. Additionally, several truncations are constructed to further characterize this CDK and determine if a specific region is responsible for PFTK2’s localization. The data show that the kinase domain itself is necessary for PFTK2’s localization to the kinetochores. Evidence suggests that PFTK2’s localization is substrate dependent, but that certain modifications may prevent the kinase from binding to its substrate. Further results and analysis are presented in this study.