β-arrestin2, a novel member of the arrestin/β-arrestin gene family

Håvard Attramadal, Jeffrey L. Arriza, Chiye Aoki, Ted M Dawson, Juan Codina, Madan M. Kwatra, Solomon H Snyder, Marc G. Caron, Robert J. Lefkowitz

Research output: Contribution to journalArticle

Abstract

Homologous or agonist-specific desensitization of β2-adrenergic receptors (β2AR) is mediated by the β-adrenergic receptor kinase (βARK) which specifically phosphorylates the agonist-occupied form of the receptor. However, the capacity of βARK-phosphorylated β2AR to stimulate Gs in a reconstituted system is only minimally impaired. Recently, a protein termed β-arrestin, was cloned from a bovine brain cDNA library and found to quench phosphorylated β2AR-coupling to Gs. Utilizing a low stringency hybridization technique to screen a rat brain cDNA library, we have now isolated cDNA clones representing two distinct β-arrestin-like genes. One of the cDNAs is the rat homolog of bovine β-arrestin (β-arrestin1). In addition, we have isolated a cDNA clone encoding a novel, β-arrestin-related protein which we have termed β-arrestin2. Overall, β-arrestin2 exhibits 78% amino acid identity with β-arrestin1. The primary structure of these proteins delineates a family of proteins that regulates receptor coupling to G proteins. The capacity of purified β-arrestin1, β-arrestin2, and arrestin to inhibit the coupling of phosphorylated receptors to their respective G proteins were assessed in a reconstituted β2AR-Gs system and in a reconstituted rhodopsin-GT system. β-Arrestin2 was equipotent to β-arrestin1 and specifically inhibited β2AR function. Conversely, arrestin inhibited rhodopsin coupling to GT, whereas β-arrestin1 and β-arrestin2 were at least 20-fold less potent in this system, β-Arrestin1 and β-arrestin2 are predominantly localized in neuronal tissues and in the spleen. However, low mRNA levels can be detected in most peripheral tissues. In the central nervous system, β-arrestin2 appears to be even more abundant than β-arrestin1. Immunohistochemical analysis of the tissue distribution of β-arrestin1 and β-arrestin2 in rat brain shows extensive, but heterogenous, neuronal labeling of the two proteins. They are found in several neuronal pathways suggesting that they have relatively broad receptor specificity regulating many G protein-coupled receptors. Furthermore, immunoelectron microscopy shows that the β-arrestins are appropriately situated at postsynaptic sites to act in concert with βARK to regulate G protein-coupled neurotransmitter receptors.

Original languageEnglish (US)
Pages (from-to)17882-17890
Number of pages9
JournalJournal of Biological Chemistry
Volume267
Issue number25
StatePublished - Sep 5 1992

Fingerprint

Arrestin
Adrenergic Receptors
Genes
GTP-Binding Proteins
Rats
Brain
Phosphotransferases
Rhodopsin
Complementary DNA
Tissue
G-Protein-Coupled Receptors
Proteins
Gene Library
Clone Cells
Arrestins
Neurotransmitter Receptor
Immunoelectron Microscopy
Neurology
Tissue Distribution
Labeling

ASJC Scopus subject areas

  • Biochemistry

Cite this

Attramadal, H., Arriza, J. L., Aoki, C., Dawson, T. M., Codina, J., Kwatra, M. M., ... Lefkowitz, R. J. (1992). β-arrestin2, a novel member of the arrestin/β-arrestin gene family. Journal of Biological Chemistry, 267(25), 17882-17890.

β-arrestin2, a novel member of the arrestin/β-arrestin gene family. / Attramadal, Håvard; Arriza, Jeffrey L.; Aoki, Chiye; Dawson, Ted M; Codina, Juan; Kwatra, Madan M.; Snyder, Solomon H; Caron, Marc G.; Lefkowitz, Robert J.

In: Journal of Biological Chemistry, Vol. 267, No. 25, 05.09.1992, p. 17882-17890.

Research output: Contribution to journalArticle

Attramadal, H, Arriza, JL, Aoki, C, Dawson, TM, Codina, J, Kwatra, MM, Snyder, SH, Caron, MG & Lefkowitz, RJ 1992, 'β-arrestin2, a novel member of the arrestin/β-arrestin gene family', Journal of Biological Chemistry, vol. 267, no. 25, pp. 17882-17890.
Attramadal H, Arriza JL, Aoki C, Dawson TM, Codina J, Kwatra MM et al. β-arrestin2, a novel member of the arrestin/β-arrestin gene family. Journal of Biological Chemistry. 1992 Sep 5;267(25):17882-17890.
Attramadal, Håvard ; Arriza, Jeffrey L. ; Aoki, Chiye ; Dawson, Ted M ; Codina, Juan ; Kwatra, Madan M. ; Snyder, Solomon H ; Caron, Marc G. ; Lefkowitz, Robert J. / β-arrestin2, a novel member of the arrestin/β-arrestin gene family. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 25. pp. 17882-17890.
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