|
|
Proc Natl Acad Sci U S A. 1993 October 15; 90(20): 9398–9402. | PMCID: PMC47575 |
Identification of additional members of human G-protein-coupled receptor kinase multigene family. B Haribabu and R Snyderman Department of Medicine, Duke University Medical Center, Durham, NC 27710. Abstract Human neutrophils express several distinct guanine nucleotide binding (G)-protein-coupled receptors that mediate their responsiveness to chemoattractants. Phosphorylation by receptor-specific and second messenger-activated protein kinases is a common mechanism for regulation of G-protein-coupled receptors. To explore the possibility that chemoattractant receptors are regulated by unique receptor kinases, we utilized PCR to identify receptor kinases in human neutrophils. Here, we report the isolation of three G-protein-coupled-receptor-kinase (GPRK)-like sequences termed GPRK5, GPRK6, and GPRK7 in addition to the beta-adrenergic receptor kinase (beta ARK) 1 and 2 isoforms (beta ARK1 and beta ARK2). Two, GPRK5 and GPRK6, showed high homology at the amino acid level to the recently identified receptor-kinase-like sequence localized close to the Huntington disease locus. GPRK7 is of interest in that it contains a DLG (Asp-Leu-Gly) amino acid motif of receptor kinases preceded by a DFD (Asp-Phe-Asp) motif. We isolated cDNAs corresponding to GPRK6; the complete sequence shows > 66% identity and 81% similarity at the amino acid level to the GPRK from the Huntington disease locus. The GPRK6 cDNA probe hybridizes to two mRNAs of 2.9 and 2.1 kb that were expressed in all the tested human tissues including HL-60 cells and neutrophils. Genomic Southern blot analysis and chromosome mapping showed that GPRK6 hybridizes to two closely related genes located on chromosomes 5 and 13 and are, therefore, distinct from the GPRK located near the Huntington disease locus on chromosome 4. The identification herein of three putative receptor kinases indicates that in addition to beta ARK and rhodopsin kinase subfamilies, there are other receptor-kinase subfamilies that regulate the broad spectrum of G-protein-coupled receptors. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Dohlman HG, Thorner J, Caron MG, Lefkowitz RJ. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–688. [PubMed]
- Klein PS, Sun TJ, Saxe CL, 3rd, Kimmel AR, Johnson RL, Devreotes PN. A chemoattractant receptor controls development in Dictyostelium discoideum. Science. 1988 Sep 16;241(4872):1467–1472. [PubMed]
- Stryer L, Bourne HR. G proteins: a family of signal transducers. Annu Rev Cell Biol. 1986;2:391–419. [PubMed]
- Hargrave PA, McDowell JH. Rhodopsin and phototransduction: a model system for G protein-linked receptors. FASEB J. 1992 Mar;6(6):2323–2331. [PubMed]
- Hausdorff WP, Caron MG, Lefkowitz RJ. Turning off the signal: desensitization of beta-adrenergic receptor function. FASEB J. 1990 Aug;4(11):2881–2889. [PubMed]
- Hausdorff WP, Bouvier M, O'Dowd BF, Irons GP, Caron MG, Lefkowitz RJ. Phosphorylation sites on two domains of the beta 2-adrenergic receptor are involved in distinct pathways of receptor desensitization. J Biol Chem. 1989 Jul 25;264(21):12657–12665. [PubMed]
- Sibley DR, Strasser RH, Caron MG, Lefkowitz RJ. Homologous desensitization of adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor. J Biol Chem. 1985 Apr 10;260(7):3883–3886. [PubMed]
- Benovic JL, Strasser RH, Caron MG, Lefkowitz RJ. 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. [PubMed]
- Palczewski K, Benovic JL. G-protein-coupled receptor kinases. Trends Biochem Sci. 1991 Oct;16(10):387–391. [PubMed]
- Palczewski K, McDowell JH, Hargrave PA. Purification and characterization of rhodopsin kinase. J Biol Chem. 1988 Oct 5;263(28):14067–14073. [PubMed]
- Benovic JL, DeBlasi A, Stone WC, Caron MG, Lefkowitz RJ. Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science. 1989 Oct 13;246(4927):235–240. [PubMed]
- Lorenz W, Inglese J, Palczewski K, Onorato JJ, Caron MG, Lefkowitz RJ. The receptor kinase family: primary structure of rhodopsin kinase reveals similarities to the beta-adrenergic receptor kinase. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8715–8719. [PubMed]
- Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ. 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]
- Ambrose C, James M, Barnes G, Lin C, Bates G, Altherr M, Duyao M, Groot N, Church D, Wasmuth JJ, et al. A novel G protein-coupled receptor kinase gene cloned from 4p16.3. Hum Mol Genet. 1992 Dec;1(9):697–703. [PubMed]
- Cassill JA, Whitney M, Joazeiro CA, Becker A, Zuker CS. Isolation of Drosophila genes encoding G protein-coupled receptor kinases. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11067–11070. [PubMed]
- Didsbury JR, Uhing RJ, Tomhave E, Gerard C, Gerard N, Snyderman R. Receptor class desensitization of leukocyte chemoattractant receptors. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11564–11568. [PubMed]
- Chuang TT, Sallese M, Ambrosini G, Parruti G, De Blasi A. High expression of beta-adrenergic receptor kinase in human peripheral blood leukocytes. Isoproterenol and platelet activating factor can induce kinase translocation. J Biol Chem. 1992 Apr 5;267(10):6886–6892. [PubMed]
- Haribabu B, Dottin RP. Identification of a protein kinase multigene family of Dictyostelium discoideum: molecular cloning and expression of a cDNA encoding a developmentally regulated protein kinase. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1115–1119. [PubMed]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed]
- Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
- Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
- Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
- Didsbury JR, Snyderman R. Molecular cloning of a new human G protein. Evidence for two Gi alpha-like protein families. FEBS Lett. 1987 Jul 13;219(1):259–263. [PubMed]
- Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. [PubMed]
- Hanks SK, Quinn AM, Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. [PubMed]
- Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. [PubMed]
- Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PubMed]
- Taylor SS. cAMP-dependent protein kinase. Model for an enzyme family. J Biol Chem. 1989 May 25;264(15):8443–8446. [PubMed]
- Adams MD, Dubnick M, Kerlavage AR, Moreno R, Kelley JM, Utterback TR, Nagle JW, Fields C, Venter JC. Sequence identification of 2,375 human brain genes. Nature. 1992 Feb 13;355(6361):632–634. [PubMed]
- Lawton MA, Yamamoto RT, Hanks SK, Lamb CJ. Molecular cloning of plant transcripts encoding protein kinase homologs. Proc Natl Acad Sci U S A. 1989 May;86(9):3140–3144. [PubMed]
- Inglese J, Koch WJ, Caron MG, Lefkowitz RJ. Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Nature. 1992 Sep 10;359(6391):147–150. [PubMed]
- Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ. Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science. 1992 Aug 28;257(5074):1264–1267. [PubMed]
- Kelly CD, Edwards Y, Johnstone AP, Harfst E, Nógrádi A, Nussey SS, Povey S, Carter ND. Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase. Ann Hum Genet. 1992 Jul;56(Pt 3):255–265. [PubMed]
- Benovic JL, Stone WC, Huebner K, Croce C, Caron MG, Lefkowitz RJ. cDNA cloning and chromosomal localization of the human beta-adrenergic receptor kinase. FEBS Lett. 1991 May 20;283(1):122–126. [PubMed]
- Kunapuli P, Benovic JL. Cloning and expression of GRK5: a member of the G protein-coupled receptor kinase family. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5588–5592. [PubMed]
|
This article has been 
