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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Benovic, JL; DeBlasi, A; Stone, WC; Caron, MG; Lefkowitz, RJ

Published Date

  • October 13, 1989

Published In

Volume / Issue

  • 246 / 4927

Start / End Page

  • 235 - 240

PubMed ID

  • 2552582

International Standard Serial Number (ISSN)

  • 0036-8075

Language

  • eng

Conference Location

  • United States