Spatiotemporal Regulation of Protein Kinase C Signaling: Control of Normal Cellular Dynamics and Mis-regulation in Cancer A dissertation submitted in partial satisfaction of the requirements for the Doctor of Philosophy in Biomedical Sciences

of the Dissertation ............................................................................................. xiii Chapter 1 Cellular Control of Protein Kinase C Signaling ................................................. 1 Chapter 2 Targeting Protein Kinase C Activity Reporter to Discrete Intracellular Regions Reveals Spatiotemporal Differences in Agonist-dependent Signaling ............................. 32 Chapter 3 A Single Residue in the C1 Domain Sensitizes Novel Protein Kinase C Isoforms to Cellular Diacylglycerol Production ............................................................... 79 Chapter 4 A Putative Cancer Driver Mutation in Protein Kinase C βII Decreases Diacylglycerol-dependent Signaling and Prevents Apoptosis in the Context of Oncogenic K-Ras .............................................................................................................................. 109 Chapter 5 Protein Kinase Cα Interacts With and Phosphorylates SAP97/DLG1 to Promote Cytoskeletal Rearrangements ........................................................................... 136 Chapter 6 Summary and Conclusions ............................................................................. 187