Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Oct 1;88(19):8715–8719. doi: 10.1073/pnas.88.19.8715

The receptor kinase family: primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase.

W Lorenz 1, J Inglese 1, K Palczewski 1, J J Onorato 1, M G Caron 1, R J Lefkowitz 1
PMCID: PMC52580  PMID: 1656454

Abstract

Light-dependent deactivation of rhodopsin as well as homologous desensitization of beta-adrenergic receptors involves receptor phosphorylation that is mediated by the highly specific protein kinases rhodopsin kinase (RK) and beta-adrenergic receptor kinase (beta ARK), respectively. We report here the cloning of a complementary DNA for RK. The deduced amino acid sequence shows a high degree of homology to beta ARK. In a phylogenetic tree constructed by comparing the catalytic domains of several protein kinases, RK and beta ARK are located on a branch close to, but separate from the cyclic nucleotide-dependent protein kinase and protein kinase C subfamilies. From the common structural features we conclude that both RK and beta ARK are members of a newly delineated gene family of guanine nucleotide-binding protein (G protein)-coupled receptor kinases that may function in diverse pathways to regulate the function of such receptors.

Full text

PDF
8715

Images in this article

8718Image
on p.8718
8718Image
on p.8718

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson S., Davis D. L., Dahlbäck H., Jörnvall H., Russell D. W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem. 1989 May 15;264(14):8222–8229. [PubMed] [Google Scholar]
  2. Benovic J. L., Bouvier M., Caron M. G., Lefkowitz R. J. Regulation of adenylyl cyclase-coupled beta-adrenergic receptors. Annu Rev Cell Biol. 1988;4:405–428. doi: 10.1146/annurev.cb.04.110188.002201. [DOI] [PubMed] [Google Scholar]
  3. Benovic J. L., DeBlasi A., Stone W. C., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science. 1989 Oct 13;246(4927):235–240. doi: 10.1126/science.2552582. [DOI] [PubMed] [Google Scholar]
  4. Benovic J. L., Mayor F., Jr, Somers R. L., Caron M. G., Lefkowitz R. J. Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase. 1986 Jun 26-Jul 2Nature. 321(6073):869–872. doi: 10.1038/321869a0. [DOI] [PubMed] [Google Scholar]
  5. Benovic J. L., Onorato J. J., Arriza J. L., Stone W. C., Lohse M., Jenkins N. A., Gilbert D. J., Copeland N. G., Caron M. G., Lefkowitz R. J. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. J Biol Chem. 1991 Aug 15;266(23):14939–14946. [PubMed] [Google Scholar]
  6. Benovic J. L., Regan J. W., Matsui H., Mayor F., Jr, Cotecchia S., Leeb-Lundberg L. M., Caron M. G., Lefkowitz R. J. Agonist-dependent phosphorylation of the alpha 2-adrenergic receptor by the beta-adrenergic receptor kinase. J Biol Chem. 1987 Dec 25;262(36):17251–17253. [PubMed] [Google Scholar]
  7. Benovic J. L., Strasser R. H., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci U S A. 1986 May;83(9):2797–2801. doi: 10.1073/pnas.83.9.2797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bouvier M., Hausdorff W. P., De Blasi A., O'Dowd B. F., Kobilka B. K., Caron M. G., Lefkowitz R. J. Removal of phosphorylation sites from the beta 2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature. 1988 May 26;333(6171):370–373. doi: 10.1038/333370a0. [DOI] [PubMed] [Google Scholar]
  9. Bownds D., Dawes J., Miller J., Stahlman M. Phosphorylation of frog photoreceptor membranes induced by light. Nat New Biol. 1972 May 24;237(73):125–127. doi: 10.1038/newbio237125a0. [DOI] [PubMed] [Google Scholar]
  10. Buczyłko J., Gutmann C., Palczewski K. Regulation of rhodopsin kinase by autophosphorylation. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2568–2572. doi: 10.1073/pnas.88.6.2568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Buechler J. A., Taylor S. S. Dicyclohexylcarbodiimide cross-links two conserved residues, Asp-184 and Lys-72, at the active site of the catalytic subunit of cAMP-dependent protein kinase. Biochemistry. 1989 Mar 7;28(5):2065–2070. doi: 10.1021/bi00431a015. [DOI] [PubMed] [Google Scholar]
  12. Buechler J. A., Taylor S. S. Identification of aspartate-184 as an essential residue in the catalytic subunit of cAMP-dependent protein kinase. Biochemistry. 1988 Sep 20;27(19):7356–7361. doi: 10.1021/bi00419a027. [DOI] [PubMed] [Google Scholar]
  13. Dohlman H. G., Thorner J., Caron M. G., Lefkowitz R. J. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–688. doi: 10.1146/annurev.bi.60.070191.003253. [DOI] [PubMed] [Google Scholar]
  14. Feng D. F., Doolittle R. F. Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol. 1987;25(4):351–360. doi: 10.1007/BF02603120. [DOI] [PubMed] [Google Scholar]
  15. Frank R. N., Cavanagh H. D., Kenyon K. R. Light-stimulated phosphorylation of bovine visual pigments by adenosine triphosphate. J Biol Chem. 1973 Jan 25;248(2):596–609. [PubMed] [Google Scholar]
  16. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fukada Y., Takao T., Ohguro H., Yoshizawa T., Akino T., Shimonishi Y. Farnesylated gamma-subunit of photoreceptor G protein indispensable for GTP-binding. Nature. 1990 Aug 16;346(6285):658–660. doi: 10.1038/346658a0. [DOI] [PubMed] [Google Scholar]
  18. Gibbs J. B. Ras C-terminal processing enzymes--new drug targets? Cell. 1991 Apr 5;65(1):1–4. doi: 10.1016/0092-8674(91)90352-y. [DOI] [PubMed] [Google Scholar]
  19. Gribskov M., Burgess R. R. Sigma factors from E. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins. Nucleic Acids Res. 1986 Aug 26;14(16):6745–6763. doi: 10.1093/nar/14.16.6745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  21. Harden T. K. Agonist-induced desensitization of the beta-adrenergic receptor-linked adenylate cyclase. Pharmacol Rev. 1983 Mar;35(1):5–32. [PubMed] [Google Scholar]
  22. Kalsow C. M., Wacker W. B. Pineal reactivity of anti-retina sera. Invest Ophthalmol Vis Sci. 1977 Feb;16(2):181–184. [PubMed] [Google Scholar]
  23. Kelleher D. J., Johnson G. L. Characterization of rhodopsin kinase purified from bovine rod outer segments. J Biol Chem. 1990 Feb 15;265(5):2632–2639. [PubMed] [Google Scholar]
  24. Kishimoto A., Nishiyama K., Nakanishi H., Uratsuji Y., Nomura H., Takeyama Y., Nishizuka Y. Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3':5'-monophosphate-dependent protein kinase. J Biol Chem. 1985 Oct 15;260(23):12492–12499. [PubMed] [Google Scholar]
  25. Korf H. W., Møller M., Gery I., Zigler J. S., Klein D. C. Immunocytochemical demonstration of retinal S-antigen in the pineal organ of four mammalian species. Cell Tissue Res. 1985;239(1):81–85. doi: 10.1007/BF00214906. [DOI] [PubMed] [Google Scholar]
  26. Kozak M. Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles. Microbiol Rev. 1983 Mar;47(1):1–45. doi: 10.1128/mr.47.1.1-45.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kozma S. C., Ferrari S., Bassand P., Siegmann M., Totty N., Thomas G. Cloning of the mitogen-activated S6 kinase from rat liver reveals an enzyme of the second messenger subfamily. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7365–7369. doi: 10.1073/pnas.87.19.7365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kwatra M. M., Benovic J. L., Caron M. G., Lefkowitz R. J., Hosey M. M. Phosphorylation of chick heart muscarinic cholinergic receptors by the beta-adrenergic receptor kinase. Biochemistry. 1989 May 30;28(11):4543–4547. doi: 10.1021/bi00437a005. [DOI] [PubMed] [Google Scholar]
  29. Kühn H., Dreyer W. J. Light dependent phosphorylation of rhodopsin by ATP. FEBS Lett. 1972 Jan 15;20(1):1–6. doi: 10.1016/0014-5793(72)80002-4. [DOI] [PubMed] [Google Scholar]
  30. Lai R. K., Perez-Sala D., Cañada F. J., Rando R. R. The gamma subunit of transducin is farnesylated. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7673–7677. doi: 10.1073/pnas.87.19.7673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lawton M. A., Yamamoto R. T., Hanks S. K., Lamb C. J. Molecular cloning of plant transcripts encoding protein kinase homologs. Proc Natl Acad Sci U S A. 1989 May;86(9):3140–3144. doi: 10.1073/pnas.86.9.3140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lohse M. J., Benovic J. L., Codina J., Caron M. G., Lefkowitz R. J. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science. 1990 Jun 22;248(4962):1547–1550. doi: 10.1126/science.2163110. [DOI] [PubMed] [Google Scholar]
  33. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lorenz W., Lomasney J. W., Collins S., Regan J. W., Caron M. G., Lefkowitz R. J. Expression of three alpha 2-adrenergic receptor subtypes in rat tissues: implications for alpha 2 receptor classification. Mol Pharmacol. 1990 Nov;38(5):599–603. [PubMed] [Google Scholar]
  35. Marin O., Meggio F., Marchiori F., Borin G., Pinna L. A. Site specificity of casein kinase-2 (TS) from rat liver cytosol. A study with model peptide substrates. Eur J Biochem. 1986 Oct 15;160(2):239–244. doi: 10.1111/j.1432-1033.1986.tb09962.x. [DOI] [PubMed] [Google Scholar]
  36. Maurer R. A. Isolation of a yeast protein kinase gene by screening with a mammalian protein kinase cDNA. DNA. 1988 Sep;7(7):469–474. doi: 10.1089/dna.1.1988.7.469. [DOI] [PubMed] [Google Scholar]
  37. Meier K., Klein C. An unusual protein kinase phosphorylates the chemotactic receptor of Dictyostelium discoideum. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2181–2185. doi: 10.1073/pnas.85.7.2181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Onorato J. J., Palczewski K., Regan J. W., Caron M. G., Lefkowitz R. J., Benovic J. L. Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase. Biochemistry. 1991 May 28;30(21):5118–5125. doi: 10.1021/bi00235a002. [DOI] [PubMed] [Google Scholar]
  39. Ovchinnikov YuA, Gubanov V. V., Khramtsov N. V., Ischenko K. A., Zagranichny V. E., Muradov K. G., Shuvaeva T. M., Lipkin V. M. Cyclic GMP phosphodiesterase from bovine retina. Amino acid sequence of the alpha-subunit and nucleotide sequence of the corresponding cDNA. FEBS Lett. 1987 Oct 19;223(1):169–173. doi: 10.1016/0014-5793(87)80530-6. [DOI] [PubMed] [Google Scholar]
  40. Palczewski K., Arendt A., McDowell J. H., Hargrave P. A. Substrate recognition determinants for rhodopsin kinase: studies with synthetic peptides, polyanions, and polycations. Biochemistry. 1989 Oct 31;28(22):8764–8770. doi: 10.1021/bi00448a013. [DOI] [PubMed] [Google Scholar]
  41. Palczewski K., McDowell J. H., Hargrave P. A. Purification and characterization of rhodopsin kinase. J Biol Chem. 1988 Oct 5;263(28):14067–14073. [PubMed] [Google Scholar]
  42. Reneke J. E., Blumer K. J., Courchesne W. E., Thorner J. The carboxy-terminal segment of the yeast alpha-factor receptor is a regulatory domain. Cell. 1988 Oct 21;55(2):221–234. doi: 10.1016/0092-8674(88)90045-1. [DOI] [PubMed] [Google Scholar]
  43. Rossmann M. G., Moras D., Olsen K. W. Chemical and biological evolution of nucleotide-binding protein. Nature. 1974 Jul 19;250(463):194–199. doi: 10.1038/250194a0. [DOI] [PubMed] [Google Scholar]
  44. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shichi H., Somers R. L. Light-dependent phosphorylation of rhodopsin. Purification and properties of rhodopsin kinase. J Biol Chem. 1978 Oct 10;253(19):7040–7046. [PubMed] [Google Scholar]
  46. Tanabe T., Nukada T., Nishikawa Y., Sugimoto K., Suzuki H., Takahashi H., Noda M., Haga T., Ichiyama A., Kangawa K. Primary structure of the alpha-subunit of transducin and its relationship to ras proteins. Nature. 1985 May 16;315(6016):242–245. doi: 10.1038/315242a0. [DOI] [PubMed] [Google Scholar]
  47. Towler D. A., Gordon J. I., Adams S. P., Glaser L. The biology and enzymology of eukaryotic protein acylation. Annu Rev Biochem. 1988;57:69–99. doi: 10.1146/annurev.bi.57.070188.000441. [DOI] [PubMed] [Google Scholar]
  48. Vaughan R. A., Devreotes P. N. Ligand-induced phosphorylation of the cAMP receptor from Dictyostelium discoideum. J Biol Chem. 1988 Oct 5;263(28):14538–14543. [PubMed] [Google Scholar]
  49. Wilden U., Kühn H. Light-dependent phosphorylation of rhodopsin: number of phosphorylation sites. Biochemistry. 1982 Jun 8;21(12):3014–3022. doi: 10.1021/bi00541a032. [DOI] [PubMed] [Google Scholar]
  50. Zoller M. J., Nelson N. C., Taylor S. S. Affinity labeling of cAMP-dependent protein kinase with p-fluorosulfonylbenzoyl adenosine. Covalent modification of lysine 71. J Biol Chem. 1981 Nov 10;256(21):10837–10842. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES