Identification of PKCα as a CK1δ C-terminal targeting kinase

CK1 family members are evolutionarily highly conserved in organisms and play crucial roles in the regulation of various cellular processes, including cell cycle, apoptosis, centrosome specific functions, and vesicle transport processes. Because of the pivotal role of CK1 and the dramatic consequences of its deregulation, tight regulatory mechanisms are indispensable to control the activity of CK1 kinase family members. In this thesis, we provide evidence of PKCα (protein kinase C alpha) as another CK1δ C-terminal targeting protein kinase. Furthermore, we show that PKCα is able to phosphorylate CK1δ at residues Ser-318, Ser-328, Thr-329, and Ser-370 within its C-terminal regulatory domain. In addition, the phosphorylation site of Ser-318 seems to have only a minor impact, whereas mutation of Ser-328, Thr-329, and Ser-370 to alanine dramatically alters the kinetic parameters of CK1δ. Additionally, PKCα-mediated phosphorylation down-regulated CK1δ kinase activity in vitro and in COLO357 cells. In summary, our results provide evidence for the regulatory relationship between PKCα and CK1δ, and contribute to a deeper understanding of cellular signal transduction networks