Cloning, expression, and chromosomal localization of β-adrenergic receptor kinase 2. A new member of the receptor kinase family

J. L. Benovic, J. J. Onorato, J. L. Arriza, W. C. Stone, M. Lohse, N. A. Jenkins, D. J. Gilbert, N. G. Copeland, M. G. Caron, R. J. Lefkowitz

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

The β-adrenergic receptor kinase (βARK) specifically phosphorylates the agonist-occupied form of the β-adrenergic and related G protein-coupled receptors. Structural features of this enzyme have been elucidated recently by the isolation of a cDNA that encodes bovine βARK. Utilizing a catalytic domain fragment of the βARK cDNA to screen a bovine brain cDNA library we have isolated a clone encoding a βARK-related enzyme which we have termed βARK2. Overall, this enzyme has 85% amino acid identity with βARK, with the protein kinase catalytic domain having 95% identity. The ability of βARK2 to phosphorylate various substrates was studied after expression in COS 7 cells. Although βARK2 is essentially equiactive with βARK in phosphorylating an acid-rich synthetic model peptide it was only ∼ 50% as active when the substrate was the agonist-occupied β2-adrenergic receptor and only ∼ 20% as active toward light-bleached rhodopsin. As with βARK, phosphorylation of the receptor substrates by βARK2 was completely stimulus dependent. RNA blot analysis with selected bovine tissues reveals an mRNA of 8 kilobases with a distribution similar to that of βARK. More detailed RNA analysis using a ribonuclease protection assay in various rat tissues suggests that the βARK2 message is present at much lower levels (typically 10-20%) than the βARK message. In the rat the βARK2 mRNA is localized predominantly in neuronal tissues although low levels are also observed in various peripheral tissues. The βARK2 gene has been localized to a region of mouse chromosome 5 whereas the βARK gene is localized on mouse chromosome 19. These data suggest the existence of a "family" of receptor kinases which may serve broadly to regulate receptor function.

Original languageEnglish (US)
Pages (from-to)14939-14946
Number of pages8
JournalJournal of Biological Chemistry
Volume266
Issue number23
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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