Beta-adrenergic receptor kinase 2 (beta-ARK-2) also known as G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ADRBK2gene.[1][2]
The beta-adrenergic receptor kinase specifically phosphorylates the agonist-occupied form of the beta-adrenergic and related G protein-coupled receptors. Overall, the beta adrenergic receptor kinase 2 has 85% amino acid similarity with beta adrenergic receptor kinase 1, with the protein kinase catalytic domain having 95% similarity. These data suggest the existence of a family of receptor kinases which may serve broadly to regulate receptor function.[2]
Discovery
The beta adrenergic receptor kinase-2 was cloned from mice and rats in 1991[3] and the human gene was cloned in 1993.[4]
Clinical significance
Gene linkage techniques were used to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder.[5] Beta adrenergic receptor kinase-2 appears to affect dopamine metabolism. Subsequent studies, while noting that chromosome 22q12 may harbor a risk gene for schizophrenia, did not find that the gene coding for beta adrenergic receptor kinase-2 was linked to schizophrenia.[6]
↑Calabrese G, Sallese M, Stornaiuolo A, Stuppia L, Palka G, De Blasi A (Feb 1995). "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics. 23 (1): 286–8. doi:10.1006/geno.1994.1497. PMID7695743.
↑Benovic JL, Onorato JJ, Arriza JL, Stone WC, Lohse M, Jenkins NA, Gilbert DJ, Copeland NG, Caron MG, Lefkowitz RJ (August 1991). "Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family". J. Biol. Chem. 266 (23): 14939–46. PMID1869533.
↑Parruti G, Ambrosini G, Sallese M, De Blasi A (January 1993). "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2". Biochem. Biophys. Res. Commun. 190 (2): 475–81. doi:10.1006/bbrc.1993.1072. PMID8427589.
↑Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR (May 2003). "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder". Mol. Psychiatry. 8 (5): 546–57. doi:10.1038/sj.mp.4001268. PMID12808434.
↑Yu SY, Takahashi S, Arinami T, Ohkubo T, Nemoto Y, Tanabe E, Fukura Y, Matsuura M, Han YH, Zhou RL, Shen YC, Matsushima E, Kojima T (February 2004). "Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families". Psychiatry Res. 125 (2): 95–104. doi:10.1016/j.psychres.2003.12.003. PMID15006433.
Benovic JL, Onorato JJ, Arriza JL, et al. (1991). "Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family". J. Biol. Chem. 266 (23): 14939–46. PMID1869533.
Parruti G, Ambrosini G, Sallese M, De Blasi A (1993). "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2". Biochem. Biophys. Res. Commun. 190 (2): 475–81. doi:10.1006/bbrc.1993.1072. PMID8427589.
Oppermann M, Freedman NJ, Alexander RW, Lefkowitz RJ (1996). "Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C". J. Biol. Chem. 271 (22): 13266–72. doi:10.1074/jbc.271.22.13266. PMID8662816.
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Barrett TB, Hauger RL, Kennedy JL, et al. (2004). "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder". Mol. Psychiatry. 8 (5): 546–57. doi:10.1038/sj.mp.4001268. PMID12808434.
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Dzimiri N, Muiya P, Andres E, Al-Halees Z (2005). "Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases". Eur. J. Pharmacol. 489 (3): 167–77. doi:10.1016/j.ejphar.2004.03.015. PMID15087239.
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