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Arrestin-Dependent Localization of Phosphodiesterases

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 219)

Abstract

Many G-protein-coupled receptors trigger the synthesis of cAMP in order to transduce signals from the membrane into the cell cytoplasm. As stimulation of each receptor type results in a specific physiological outcome, compartmentalization of proteins that make, break, and are activated by cAMP underpin receptor-specific responses. Until 2002, it was thought that static compartmentalization of phosphodiesterase 4 (PDE4), conferred by N-terminal targeting sequences, was one way to shape intricate cAMP gradients that formed after receptor activation. Discovery of the PDE4–β-arrestin complex represented a major breakthrough in cAMP signaling, as it spurred the initial realization that PDE4s could be transported to sites of high cAMP to orchestrate destruction of the second messenger at the same time as the receptor’s signal to the G-protein is silenced. This chapter charts the scientific process that led to the discovery and characterization of the PDE4–β-arrestin interaction and discusses the known functions of this signaling complex.

Keywords

Phosphodiesterase type 4 (PDE4) Cyclic AMP Compartmentalization Peptide array Protein kinase A (PKA) β-arrestin 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life SciencesUniversity of GlasgowGlasgowUK

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