Beta-adrenergic receptor kinase: primary structure delineates a multigene family.
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.
Benovic
J L
JL
Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
DeBlasi
A
A
Stone
W C
WC
Caron
M G
MG
Lefkowitz
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009928:Organ Specificity; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D051552:beta-Adrenergic Receptor Kinases
D011943:Receptors, Adrenergic, beta; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases