Neuronal Effectors for Pim Kinases
Principal Investigators: PÄIVI KOSKINEN, ELEANOR COFFEY
Turku Centre for Biotechnology
Cell growth, differentiation and death are strictly controlled by extracellular signals transmitted from the cell surface to the nucleus. The Koskinen group has previously investigated the roles of Pim family protein kinases in hematopoietic cell signalling and survival, but has recently extended these studies also to cells of the nervous system, where interesting expression patterns for pim family genes have been observed. Our further investigations are aimed towards identification and functional characterization of novel Pim substrates from the brain, taking advantage of a powerful phosphoproteomics-based screen developed in the Coffey group to identify novel protein kinase targets from brain extracts. We will then examine the effects of Pim kinases and their substrates on the regulation of cytokine and neurotransmitter synthesis and secretion. We will also analyse the involvement of Pim kinases and their substrates in neuronal cell survival in response to oxidative stress or excitotoxic insult. For these studies, we will set up a system based on RNA interference that will allow us to specifically inactivate one or more of the endogenously expressed Pim family genes or novel Pim targets. The studies will initiated in the neuron-like PC12 cell model and later continued in cultured neurons isolated from rodents. Finally we will extend our investigation to an animal model of Parkinson's disease to find out whether Pim kinases can prevent the loss of functional dopaminergic neurons from the substantia nigra. Thus, our basic neurobiological studies on signalling pathways regulating the growth, differentiation and survival of neuronal cells may contribute to the understanding of progression of neurodegenerative diseases such as Parkinson's disease and may provide a basis for development of tools for future therapeutic intervention in such disorders.
Contact: paivi.koskinen(at)btk.fi, tel. +358 2 333 8044