Beta adrenergic receptor kinase-2

Adrenergic, beta, receptor kinase 2
Identifiers
Symbols ADRBK2; BARK2; GRK3
External IDs OMIM: 109636 MGI: 87941 HomoloGene: 21072 GeneCards: ADRBK2 Gene
EC number 2.7.11.15
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 157 320129
Ensembl ENSG00000100077 ENSMUSG00000042249
UniProt P35626 Q8BVT9
RefSeq (mRNA) NM_005160.3 NM_001035531
RefSeq (protein) NP_005151.2 NP_001030608
Location (UCSC) Chr 22:
25.96 – 26.12 Mb		 Chr 5:
113.34 – 113.44 Mb
PubMed search [1] [2]

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]

Contents

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. ^ a b "Entrez Gene: ADRBK2 adrenergic, beta, receptor kinase 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=157. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2242619. 

Further reading

External links