Feedback Regulation of G Protein-coupled Receptor Signaling by GRKs and Arrestins

Overview

Journal Semin Cell Dev Biol

Specialties Cell Biology
Reproductive Medicine

Date 2016 Jan 17

PMID 26773211

Citations 28

Authors

Joseph B Black

Richard T Premont

Yehia Daaka

Affiliations

Soon will be listed here.

Abstract

GPCRs are ubiquitous in mammalian cells and present intricate mechanisms for cellular signaling and communication. Mechanistically, GPCR signaling was identified to occur vectorially through heterotrimeric G proteins that are negatively regulated by GRK and arrestin effectors. Emerging evidence highlights additional roles for GRK and Arrestin partners, and establishes the existence of interconnected feedback pathways that collectively define GPCR signaling. GPCRs influence cellular dynamics and can mediate pathologic development, such as cancer and cardiovascular remolding. Hence, a better understanding of their overall signal regulation is of great translational interest and research continues to exploit the pharmacologic potential for modulating their activity.

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References

Decaillot F, Befort K, Filliol D, Yue S, Walker P, Kieffer B . Opioid receptor random mutagenesis reveals a mechanism for G protein-coupled receptor activation. Nat Struct Biol. 2003; 10(8):629-36. DOI: 10.1038/nsb950. View

Luttrell L, Roudabush F, Choy E, Miller W, Field M, Pierce K . Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci U S A. 2001; 98(5):2449-54. PMC: 30158. DOI: 10.1073/pnas.041604898. View

Shinohara T, Dietzschold B, Craft C, Wistow G, Early J, Donoso L . Primary and secondary structure of bovine retinal S antigen (48-kDa protein). Proc Natl Acad Sci U S A. 1987; 84(20):6975-9. PMC: 299211. DOI: 10.1073/pnas.84.20.6975. View

Nobles K, Xiao K, Ahn S, Shukla A, Lam C, Rajagopal S . Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin. Sci Signal. 2011; 4(185):ra51. PMC: 3415961. DOI: 10.1126/scisignal.2001707. View

Luttrell L, Ferguson S, Daaka Y, Miller W, Maudsley S, Della Rocca G . Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science. 1999; 283(5402):655-61. DOI: 10.1126/science.283.5402.655. View

Perry S, Baillie G, Kohout T, McPhee I, Magiera M, Ang K . Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science. 2002; 298(5594):834-6. DOI: 10.1126/science.1074683. View

Tsao P, Cao T, von Zastrow M . Role of endocytosis in mediating downregulation of G-protein-coupled receptors. Trends Pharmacol Sci. 2001; 22(2):91-6. DOI: 10.1016/s0165-6147(00)01620-5. View

Qian B, Soyer O, Neubig R, Goldstein R . Depicting a protein's two faces: GPCR classification by phylogenetic tree-based HMMs. FEBS Lett. 2003; 554(1-2):95-9. DOI: 10.1016/s0014-5793(03)01112-8. View

Pawson T . Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell. 2004; 116(2):191-203. DOI: 10.1016/s0092-8674(03)01077-8. View

10.

Murakami A, Yajima T, Sakuma H, McLaren M, Inana G . X-arrestin: a new retinal arrestin mapping to the X chromosome. FEBS Lett. 1993; 334(2):203-9. DOI: 10.1016/0014-5793(93)81712-9. View

11.

Salazar N, Chen J, Rockman H . Cardiac GPCRs: GPCR signaling in healthy and failing hearts. Biochim Biophys Acta. 2007; 1768(4):1006-18. PMC: 1892229. DOI: 10.1016/j.bbamem.2007.02.010. View

12.

Palczewski K, Orban T . From atomic structures to neuronal functions of g protein-coupled receptors. Annu Rev Neurosci. 2013; 36:139-64. PMC: 4594856. DOI: 10.1146/annurev-neuro-062012-170313. View

13.

Lafarga V, Aymerich I, Tapia O, Mayor Jr F, Penela P . A novel GRK2/HDAC6 interaction modulates cell spreading and motility. EMBO J. 2011; 31(4):856-69. PMC: 3280560. DOI: 10.1038/emboj.2011.466. View

14.

Neves S, Ram P, Iyengar R . G protein pathways. Science. 2002; 296(5573):1636-9. DOI: 10.1126/science.1071550. View

15.

Daaka Y, Pitcher J, Richardson M, Stoffel R, Robishaw J, Lefkowitz R . Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases. Proc Natl Acad Sci U S A. 1997; 94(6):2180-5. PMC: 20061. DOI: 10.1073/pnas.94.6.2180. View

16.

Pierce K, Premont R, Lefkowitz R . Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002; 3(9):639-50. DOI: 10.1038/nrm908. View

17.

Owens D, Lumpkin E . Diversification and specialization of touch receptors in skin. Cold Spring Harb Perspect Med. 2014; 4(6). PMC: 4031957. DOI: 10.1101/cshperspect.a013656. View

18.

Moore C, Milano S, Benovic J . Regulation of receptor trafficking by GRKs and arrestins. Annu Rev Physiol. 2006; 69:451-82. DOI: 10.1146/annurev.physiol.69.022405.154712. View

19.

Chakraborty P, Zhang Y, Coomes A, Kim W, Stupay R, Lynch L . G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer. Cancer Res. 2014; 74(13):3489-500. DOI: 10.1158/0008-5472.CAN-13-2708. View

20.

Pitcher J, Hall R, Daaka Y, Zhang J, Ferguson S, Hester S . The G protein-coupled receptor kinase 2 is a microtubule-associated protein kinase that phosphorylates tubulin. J Biol Chem. 1998; 273(20):12316-24. DOI: 10.1074/jbc.273.20.12316. View