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Science 13 October 1989:
Vol. 246. no. 4927, pp. 235 - 240
DOI: 10.1126/science.2552582
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Articles

Science, Vol 246, Issue 4927, 235-240
Copyright © 1989 by American Association for the Advancement of Science

articles

Beta-adrenergic receptor kinase: primary structure delineates a multigene family

JL Benovic, A DeBlasi, WC Stone, MG Caron, and RJ Lefkowitz

Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.

The beta-adrenergic receptor kinase (beta-ARK), which specifically phosphorylates only the agonist-occupied form of the beta-adrenergic and closely related receptors, appears to be important in mediating rapid agonist-specific (homologous) desensitization. The structure of this enzyme was elucidated by isolating clones from a bovine brain complementary DNA library through the use of oligonucleotide probes derived from partial amino acid sequence. The beta-ARK cDNA codes for a protein of 689 amino acids (79.7 kilodaltons) with a protein kinase catalytic domain that bears greatest sequence similarity to protein kinase C and the cyclic adenosine monophosphate (cyclic AMP)--dependent protein kinase. When this clone was inserted into a mammalian expression vector and transfected into COS-7 cells, a protein that specifically phosphorylated the agonist-occupied form of the beta 2-adrenergic receptor and phosphorylated, much more weakly, the light-bleached form of rhodopsin was expressed. RNA blot analysis revealed a messenger RNA of four kilobases with highest amounts in brain and spleen. Genomic DNA blot analysis also suggests that beta-ARK may be the first sequenced member of a multigene family of receptor kinases.


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