Biology: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. ↑ "Chromosome mapping of the human arrestin (SAG), beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2) genes". Genomics 23 (1): 286–8. Feb 1995. doi:10.1006/geno.1994.1497. PMID 7695743. 
  2. ↑ 2.0 2.1 "Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=157. 
  3. ↑ "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. August 1991. PMID 1869533. 
  4. ↑ "Molecular cloning, functional expression and mRNA analysis of human beta-adrenergic receptor kinase 2". Biochem. Biophys. Res. Commun. 190 (2): 475–81. January 1993. doi:10.1006/bbrc.1993.1072. PMID 8427589. 
  5. ↑ "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. May 2003. doi:10.1038/sj.mp.4001268. PMID 12808434. 
  6. ↑ "Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families". Psychiatry Res 125 (2): 95–104. February 2004. 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. PMID 18274673. 

Further reading

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