Role of Protein Phosphorylation in the Regulation of Neuronal Sensitivity.

摘要

The project reported here focuses on the regulation of neuronal sensitivity by a novel class of protein kinase, an ecto-protein kinase which phosphorylates proteins at the cell surface by extracellular ATP. The progress we have made in this project includes the development of novel experimental paradigms for the determination of ecto-protein kinase and its substrates in cultured neuronal cells. We used these paradigms in the conclusive identification of the surface phosphoproteins in primary neurons cultured from embryonic brain and in PC 12 cloned neuronal cells induced to differentiate by nerve growth factor (NGF). We have determined which of these surface phosphoproteins are regulated by NGF. We have also identified a specific phosphorylation system at the surface-of CNS neurons involved in neurogenesis. These specific phosphoproteins are at the focus of continued studies on the role of ecto kinase in synaptic plasticity. A pilot investigation conducted as part of this project revealed that the naturally occurring ether-phospholipid Platelet Activating Factor (PAF) induces Long-Term Potentiation (LTP) in hippocampal slices, and may have an important modulatory role in the process of memory formation.