BBB Seminar: Biokjemisk Kollokvium (NBS, Bergen Division): Peter Parker
Mapping, monitoring and meddling in PKC action
Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, UK
Signal transducers are key to relaying information within cells and triggering actions appropriate to their differentiated function. The progression of cells towards autonomous behaviour is a characteristic of tumour cells and it is now well established that this autonomy of action is associated with somatic changes in signalling pathways that normally determine growth, survival, apoptosis, migration, genome stability and related functions typically aberrant in cancer.
Amongst the various classes of transducers, the abundant kinases provide critical nodes in the signalling network. With the clarity of hindsight it is no surprise that specific kinases are frequently mutated or up-regulated in cancer, events which provide both insights into key functions responsible for disease/disease progression and also afford excellent opportunities for targeted therapeutic intervention.
Amongst the serine/threonine protein kinases associated with tumour promoting functions is the protein kinase C (PKC) superfamily. This class of proteins comprise 12 distinct genes, which give rise to 4 distinct PKC subclasses each with characteristic regulatory properties. Analysis of the physiological and potential pathological roles of these proteins has identified a series of functions that suggest appropriately selective interventions may provide beneficial therapeutic strategies.
Two areas of particular interest for the Parker Laboratory have centred upon PKC regulation of the cell cycle and migration/invasion - both characteristically dysregulated in disease. While PKCe has been shown to regulate cell cycle, various members of the PKC family have been implicated in migratory behaviour. Descriptions of these relationships (mapping PKC pathways), consideration of intervention (meddling in PKC function) and means of assessing pathway functions (monitoring PKC action) will be discussed.
Host: Stein Ove Døskeland, Department of Biomedicine