SIGNAL COMPARTMENTALIZATION ß-Arrestin Regulation of Cyclic AMP Signaling

A molecular understanding of the spatiotemporal regulation of various intracellular signals has revealed how tightly controlled this process can be. For example, the intracellular second messenger adenosine 3',5'-monophosphate (cAMP) is generated in response to the activation of some G protein-coupled receptors, and cAMP microdomains are thought to be generated by the rate and location of cAMP degradation by phosphodiesterases (PDEs). The cAMP signals generated by activated ß₂-adrenergic receptors are quenched when the cytosolic molecule ß-arrestin associates with and desensitizes the receptors from further agonist stimulation. Perry et al. now report that ß-arrestins not only blunt the rate of cAMP generation but also promote cAMP degradation by recruiting PDEs to activated receptors at the plasma membrane. This coordinated activity may allow ß-arrestins to restrict the extent of cAMP-dependent activities at the cell surface.

S. J. Perry, G. S. Baillie, T. A. Kohout, I. McPhee, M. M. Magiera, K. L. Ang, W. E. Miller, A. J. McLean, M. Conti, M. D. Houslay, R. J. Lefkowitz, Targeting of cyclic AMP degradation to ß₂-adrenergic receptors by ß-arrestins. Science 298, 834-836 (2002). [Abstract] [Full Text]

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REPORTS
Targeting of Cyclic AMP Degradation to ₂-Adrenergic Receptors by -Arrestins

Stephen J. Perry, George S. Baillie, Trudy A. Kohout, Ian McPhee, Maria M. Magiera, Kok Long Ang, William E. Miller, Alison J. McLean, Marco Conti, Miles D. Houslay, and Robert J. Lefkowitz (25 October 2002)
Science 298 (5594), 834. [DOI: 10.1126/science.1074683]
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