cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP).
The second messenger cAMP plays a central role in mediating vascular smooth muscle relaxation in response to vasoactive transmitters and in strengthening endothelial cell-cell junctions that regulate the movement of solutes, cells and macromolecules between the blood and the surrounding tissue. The vasculature expresses three cAMP effector proteins: PKA (protein kinase A), CNG (cyclic-nucleotide-gated) ion channels, and the most recently discovered Epacs (exchange proteins directly activated by cAMP). Epacs are a family of GEFs (guanine-nucleotide-exchange factors) for the small Ras-related GTPases Rap1 and Rap2, and are being increasingly implicated as important mediators of cAMP signalling, both in their own right and in parallel with the prototypical cAMP target PKA. In the present paper, we review what is currently known about the role of Epac within blood vessels, particularly with regard to the regulation of vascular tone, endothelial barrier function and inflammation.
*Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, U.K.
Owain Llŷr
OL
Roberts
*Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, U.K.
Caroline
C
Dart
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D002199:Capillary Permeability; D002448:Cell Adhesion; D002465:Cell Movement; D000242:Cyclic AMP / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D015290:Second Messenger Systems
D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; D000242:Cyclic AMP