Beta adrenergic receptor kinase-2

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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 ADRBK2 gene.[1][2]

Function

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]

It has been associated with WHIM syndrome.[7]

References

  1. 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. PMID 7695743.
  2. 2.0 2.1 "Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2".
  3. 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. PMID 1869533.
  4. 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. PMID 8427589.
  5. 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. PMID 12808434.
  6. 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. PMID 15006433.
  7. Balabanian K, Levoye A, Klemm L, et al. (March 2008). "Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling". J. Clin. Invest. 118 (3): 1074–84. doi:10.1172/JCI33187. PMC 2242619. PMID 18274673.

Further reading

External links


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