The Department of Biomedicine

BBB seminar: Kjetil Tasken

Spatiotemporal regulation of cyclic AMP signaling processes in the heart and the immune system

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Kjetil Tasken
Biotechnology Centre of Oslo, University of Oslo

The cyclic AMP-protein kinase A (cAMP-PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. A kinase anchoring proteins (AKAPs) target PKA to specific substrates and distinct subcellular compartments providing spatial and temporal specificity for mediation of biological effects channeled through the cAMP-PKA pathway. A beta-adrenergic receptor/cAMP/PKA signaling pathway regulates heart rate and contractility. We have identified a supramolecular complex consisting of the Ca2+-ATPase SERCA2, its negative regulator phospholamban (PLB), an A-kinase anchoring protein and protein kinase A (PKA) in cardiac myocytes. We show that AKAP18 serves as a scaffold that co-ordinates PKA phosphorylation of PLB and the adrenergic effect on Ca2+ re-uptake. In the immune system we have shown that cAMP regulates immune responses activated through the T cell receptor (TCR) through a PKA-Csk pathway. PKA type I is targeted to the TCR-CD3 complex during T cell activation via an AKAP that serves as a scaffold for the pathway in lipid rafts of the plasma membrane during T-cell activation.

Host: Marit Bakke, Department of Biomedicine