Arrestins and Protein Ubiquitination - Progress in Molecular Biology and Translational Science - page 169

CHAPTER SEVEN

Arrestins and Protein
Ubiquitination

†
* Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
† Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA

,

Reddy Peera Kommaddi * , Sudha K. Shenoy *

Contents
1. Introduction 176

1.1 Arrestins: Adaptors for receptors and effectors 176

1.2 Ubiquitination: A pleiotropic posttranslational modification 178

1.3 Deubiquitination 181

2. Ubiquitination of Arrestins 182

2.1 Mechanisms: Modification by E3 ubiquitin ligase(s) 182

2.2 Biology: Kinetics and stability 183

2.3 Functional effects 186

3. Deubiquitination of Arrestins 187

4. Arrestins Act as Adaptors for Ubiquitination 189

4.1 7TMRs 190

4.2 Other receptors 191

4.3 Ion channels 192

4.4 Enzymes and other proteins 192

5. Arrestins and Seven-Transmembrane Receptor Deubiquitination 193

6. Arrestin-Like Proteins 194

6.1 Aspergillus nidulans 194

6.2 Saccharomyces cerevisiae 196

6.3 Mammalian arrestin domain-containing proteins 196

7. Conclusions 198

Acknowledgment 199

References 199

Abstract
The adaptor proteins, b-arrestins 1 and 2, were originally identified as inhibitors of
G protein signaling at the seven-transmembrane receptors (7TMRs, also called
G protein-coupled receptors or GPCRs). Subsequent studies have established b-arrestins
as critical multifunctional 7TMR adaptors that mediate receptor trafficking and activate
G protein-independent signaling pathways. 7TMR activation leads not only to the
recruitment of arrestin proteins upon phosphorylation by GPCR kinases but also to