The Department of Biomedicine

BBB webinar: Stein Ove Døskeland NB! Cancelled

Cyclic AMP signaling, with emphasis on the role of Epac (RapGef 3,4,2) in Epac KO mice

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Stein Ove Døskeland
Department of Biomedicine, University of Bergen

The archetype second messenger cyclic AMP has a variety of actions in mammalian cells, mostly mediated by cAMP-activated protein kinase (PKAIa,b,IIa,b). Some cAMP actions that could not be explained by PKA activation alone, appear to be mediated by cAMP-stimulated activators (Epac1,2; RapGef3,4) of the small G-protein Rap.

We developed cAMP analogs discriminating between PKA and Epac. They led to important findings regarding the ability of Epac1 to increase cell adherence in vitro, but had also off-target effects.

We turned, therefore, to Epac1 and Epac2 KO mice in in vivo studies. Epac1 acted in vivo to preserve intravascular fluid by: 1) tightening the endothelial barrier, 2) decreasing bleeding, and 3) decreasing loss of water in the urine (by stabilizing urinary collecting duct tight junctions). Epac2 optimized liver regeneration, possibly by lowering oxidative damage. 

The talk will attempt to show how Epac in general may act complementarily with PKA to fine-tune cAMP actions.

Chairperson: Marit Bakke, Department of Biomedicine