A beta-adrenergic receptor kinase dominant negative mutant attenuates desensitization of the beta 2-adrenergic receptor.

Publication/Presentation Date

5-6-1994

Abstract

The beta-adrenergic receptor kinase (beta ARK) specifically phosphorylates the activated form of the beta 2-adrenergic receptor (beta 2AR) and related G protein-coupled receptors. To further elucidate the role of beta ARK in receptor desensitization, we generated a beta ARK dominant negative mutant by converting an invariant lysine residue in the protein kinase catalytic domain to an arginine. Expressed and purified beta ARK-K220R was able to inhibit wild type beta ARK phosphorylation of the beta 2AR in vitro. When stably transfected into human bronchial epithelial BEAS-2B cells, beta ARK-K220R promoted a > 2-fold increase in beta-agonist-stimulated cAMP production without affecting beta 2AR sequestration. In contrast, beta ARK-K220R had no effect on the desensitization of the prostaglandin E2 receptor response in BEAS-2B cells. These findings directly demonstrate a role for beta ARK in desensitization of the beta 2AR in intact cells and establish the potential utility of using dominant negative mutants to elucidate the substrate specificity of G protein-coupled receptor kinases.

Volume

269

Issue

18

First Page

13084

Last Page

13087

ISSN

0021-9258

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

8175732

Department(s)

Administration and Leadership

Document Type

Article

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