Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein).

Benovic, JL

Kühn, H

Weyand, I

Codina, J

Caron, MG

Lefkowitz, RJ

United States

2013-09-24T17:54:00Z

1987-12

The beta-adrenergic receptor kinase is an enzyme, possibly analogous to rhodopsin kinase, that multiply phosphorylates the beta-adrenergic receptor only when it is occupied by stimulatory agonists. Since this kinase may play an important role in mediating the process of homologous, or agonist-specific, desensitization, we investigated the functional consequences of receptor phosphorylation by the kinase and possible analogies with the mechanism of action of rhodopsin kinase. Pure hamster lung beta 2-adrenergic receptor, reconstituted in phospholipid vesicles, was assessed for its ability to mediate agonist-promoted stimulation of the GTPase activity of coreconstituted stimulatory guanine nucleotide-binding regulatory protein. When the receptor was phosphorylated by partially (approximately 350-fold) purified preparations of beta-adrenergic receptor kinase, as much as 80% inactivation of its functional activity was observed. However, the use of more highly purified enzyme preparations led to a dramatic decrease in the ability of phosphorylation to inactivate the receptor such that pure enzyme preparations (approximately 20,000-fold purified) caused only minimal (approximately 1off/- 7%) inactivation. Addition of pure retinal arrestin (48-kDa protein or S antigen), which is involved in enhancing the inactivating effect of rhodopsin phosphorylation by rhodopsin kinase, led to partial restoration of the functional effect of beta-adrenergic receptor kinase-promoted phosphorylation (41 +/- 3% inactivation). These results suggest the possibility that a protein analogous to retinal arrestin may exist in other tissues and function in concert with beta-adrenergic receptor kinase to regulate the activity of adenylate cyclase-coupled receptors.

http://www.ncbi.nlm.nih.gov/pubmed/2827157

0027-8424

https://hdl.handle.net/10161/7874

eng

Proceedings of the National Academy of Sciences

Proc Natl Acad Sci U S A

Animals

Antigens

Arrestin

Cyclic AMP-Dependent Protein Kinases

Eye Proteins

GTP-Binding Proteins

Humans

In Vitro Techniques

Phosphoproteins

Phosphorylation

Protein Kinases

Receptors, Adrenergic, beta

Retina

beta-Adrenergic Receptor Kinases

Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein).

Journal article

Lefkowitz, RJ|0000-0003-1472-7545

http://www.ncbi.nlm.nih.gov/pubmed/2827157

8879

8882

24

Basic Science Departments

Biochemistry

Cell Biology

Chemistry

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Institute for Brain Sciences

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Neurobiology

Pathology

School of Medicine

Trinity College of Arts & Sciences

University Institutes and Centers

Published

84