Molecular cloning and expression of GRK6. A new member of the G protein-coupled receptor kinase family.

作者: J.L. Benovic , J Gomez

DOI: 10.1016/S0021-9258(19)36546-9

关键词: Protein kinase ABeta adrenergic receptor kinaseKinaseRhodopsin kinaseG-Protein-Coupled Receptor Kinase 5G protein-coupled receptor kinaseBiologyRhodopsinMolecular biologyG protein

摘要: Abstract G protein-coupled receptor kinases (GRK), such as the beta-adrenergic kinase (beta ARK) and rhodopsin kinase, specifically phosphorylate activated form of receptors. To identify additional members GRK family, we screened a human heart cDNA library by low stringency hybridization using catalytic domains two beta ARK isoforms. Here report isolation that encodes 576-amino-acid protein termed GRK6, has significant homology with GRK5 (70.1% amino acid identity), IT11 (68.5%), (47.1%), (37.4%). RNA blot analysis GRK6 selected tissues reveals distinct mRNAs 3 2.4 kilobases distribution very similar to (i.e. brain, skeletal muscle > pancreas heart, lung, kidney, placenta liver). overexpressed in Sf9 insect cells baculovirus system, was able both 2-adrenergic stimulus-dependent fashion, although it significantly less active then on these substrates. These data extend family GRKs suggest may have substrate specificity quite from kinase.

参考文章(39)
R.M. Richardson, C. Kim, J.L. Benovic, M.M. Hosey, Phosphorylation and desensitization of human m2 muscarinic cholinergic receptors by two isoforms of the beta-adrenergic receptor kinase. Journal of Biological Chemistry. ,vol. 268, pp. 13650- 13656 ,(1993) , 10.1016/S0021-9258(19)38697-1
F Mayor, J L Benovic, M G Caron, R J Lefkowitz, Somatostatin induces translocation of the beta-adrenergic receptor kinase and desensitizes somatostatin receptors in S49 lymphoma cells. Journal of Biological Chemistry. ,vol. 262, pp. 6468- 6471 ,(1987) , 10.1016/S0021-9258(18)48265-8
S.B. Liggett, J Ostrowski, L.C. Chesnut, H Kurose, J.R. Raymond, M.G. Caron, R.J. Lefkowitz, Sites in the third intracellular loop of the alpha 2A-adrenergic receptor confer short term agonist-promoted desensitization. Evidence for a receptor kinase-mediated mechanism. Journal of Biological Chemistry. ,vol. 267, pp. 4740- 4746 ,(1992) , 10.1016/S0021-9258(18)42894-3
J.L. Benovic, J.J. Onorato, J.L. Arriza, W.C. Stone, M. Lohse, N.A. Jenkins, D.J. Gilbert, N.G. Copeland, M.G. Caron, R.J. Lefkowitz, Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. Journal of Biological Chemistry. ,vol. 266, pp. 14939- 14946 ,(1991) , 10.1016/S0021-9258(18)98568-6
J L Benovic, J W Regan, H Matsui, F Mayor, S Cotecchia, L M Leeb-Lundberg, M G Caron, R J Lefkowitz, Agonist-dependent phosphorylation of the alpha 2-adrenergic receptor by the beta-adrenergic receptor kinase. Journal of Biological Chemistry. ,vol. 262, pp. 17251- 17253 ,(1987) , 10.1016/S0021-9258(18)45367-7
H. Shichi, R.L. Somers, Light-dependent phosphorylation of rhodopsin. Purification and properties of rhodopsin kinase. Journal of Biological Chemistry. ,vol. 253, pp. 7040- 7046 ,(1978) , 10.1016/S0021-9258(17)38026-2
M.M. Kwatra, D.A. Schwinn, J. Schreurs, J.L. Blank, C.M. Kim, J.L. Benovic, J.E. Krause, M.G. Caron, R.J. Lefkowitz, The substance P receptor, which couples to Gq/11, is a substrate of beta-adrenergic receptor kinase 1 and 2. Journal of Biological Chemistry. ,vol. 268, pp. 9161- 9164 ,(1993) , 10.1016/S0021-9258(18)98326-2
J Inglese, J F Glickman, W Lorenz, M G Caron, R J Lefkowitz, Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. Journal of Biological Chemistry. ,vol. 267, pp. 1422- 1425 ,(1992) , 10.1016/S0021-9258(18)45960-1