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Arrestin Interaction with E3 Ubiquitin Ligases and Deubiquitinases: Functional and Therapeutic Implications

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Arrestins - Pharmacology and Therapeutic Potential

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

Abstract

Arrestins constitute a small family of four homologous adaptor proteins (arrestins 1–4), which were originally identified as inhibitors of signal transduction elicited by the seven-transmembrane G protein-coupled receptors. Currently arrestins (especially arrestin2 and arrestin3; also called β-arrestin1 and β-arrestin2) are known to be activators of cell signaling and modulators of endocytic trafficking. Arrestins mediate these effects by binding to not only diverse cell-surface receptors but also by associating with a variety of critical signaling molecules in different intracellular compartments. Thus, the functions of arrestins are multifaceted and demand interactions with a host of proteins and require an array of selective conformations. Furthermore, receptor ligands that specifically induce signaling via arrestins are being discovered and their physiological roles are emerging. Recent evidence suggests that the activity of arrestin is regulated in space and time by virtue of its dynamic association with specific enzymes of the ubiquitination pathway. Ubiquitin-dependent, arrestin-mediated signaling could serve as a potential platform for developing novel therapeutic strategies to target transmembrane signaling and physiological responses.

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Acknowledgments

This work was supported by an NIH grant HL 080525 (S.K.S) and a grant-in-aid from the American Heart Association (S.K.S).

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Sudha K. Shenoy

  2. Department of Cell Biology, Duke University Medical Center, Durham, NC, USA

    Sudha K. Shenoy

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Correspondence to Sudha K. Shenoy .

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Editors and Affiliations

  1. Professor of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

    Vsevolod V. Gurevich

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Shenoy, S.K. (2014). Arrestin Interaction with E3 Ubiquitin Ligases and Deubiquitinases: Functional and Therapeutic Implications. In: Gurevich, V. (eds) Arrestins - Pharmacology and Therapeutic Potential. Handbook of Experimental Pharmacology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41199-1_10

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