Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice

Howard A. Rockman, Dong-Ju Choi, Nadeem U. Rahman, Shahab A. Akhter, Robert J. Lefkowitz, Walter J. Koch

Research output: Contribution to journalArticleResearchpeer-review

168 Citations (Scopus)

Abstract

Transgenic mice were generated wit h cardiacspecific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals overexpressing GRK5 showed marked β-adrenergic receptor desensitization in both the anesthetized and conscious state compared with nontransgenic control mice, while the contractile response to angiotensin II receptor stimulation was unchanged. In contrast, the angiotensin II-induced rise in contractility was significantly attenuated in transgenic mice overexpressing the β- adrenergic receptor kinase-1, another member of the GRK family. These data suggest that myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors and demonstrate that receptor specificity of the GRKs may be important in determining the physiological phenotype.

Original languageEnglish
Pages (from-to)9954-9959
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number18
DOIs
StatePublished - 3 Sep 1996

Fingerprint

G-Protein-Coupled Receptor Kinase 5
Transgenic Mice
Adrenergic Receptors
Wit and Humor
Angiotensin Receptors
Protein-Serine-Threonine Kinases
G-Protein-Coupled Receptors
Angiotensin II
Phosphotransferases
Phenotype
Psychologic Desensitization

Keywords

  • adenylylcyclase
  • angiotensin II receptor
  • myocardial contractility
  • β-adrenergic receptor kinase

Cite this

Rockman, Howard A. ; Choi, Dong-Ju ; Rahman, Nadeem U. ; Akhter, Shahab A. ; Lefkowitz, Robert J. ; Koch, Walter J. / Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 18. pp. 9954-9959.
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Receptor-specific in vivo desensitization by the G protein-coupled receptor kinase-5 in transgenic mice. / Rockman, Howard A.; Choi, Dong-Ju; Rahman, Nadeem U.; Akhter, Shahab A.; Lefkowitz, Robert J.; Koch, Walter J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 18, 03.09.1996, p. 9954-9959.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Rockman, Howard A.

AU - Choi, Dong-Ju

AU - Rahman, Nadeem U.

AU - Akhter, Shahab A.

AU - Lefkowitz, Robert J.

AU - Koch, Walter J.

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AB - Transgenic mice were generated wit h cardiacspecific overexpression of the G protein-coupled receptor kinase-5 (GRK5), a serine/threonine kinase most abundantly expressed in the heart compared with other tissues. Animals overexpressing GRK5 showed marked β-adrenergic receptor desensitization in both the anesthetized and conscious state compared with nontransgenic control mice, while the contractile response to angiotensin II receptor stimulation was unchanged. In contrast, the angiotensin II-induced rise in contractility was significantly attenuated in transgenic mice overexpressing the β- adrenergic receptor kinase-1, another member of the GRK family. These data suggest that myocardial overexpression of GRK5 results in selective uncoupling of G protein-coupled receptors and demonstrate that receptor specificity of the GRKs may be important in determining the physiological phenotype.

KW - adenylylcyclase

KW - angiotensin II receptor

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KW - β-adrenergic receptor kinase

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