Beta adrenergic receptor kinase

Adrenergic, beta, receptor kinase 1

PDB rendering based on 1bak.
Identifiers
Symbols ADRBK1; BARK1; BETA-ARK1; FLJ16718; GRK2
External IDs OMIM: 109635 MGI: 87940 HomoloGene: 1223 GeneCards: ADRBK1 Gene
EC number 2.7.11.15
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 156 110355
Ensembl ENSG00000173020 ENSMUSG00000024858
UniProt P25098 Q3U5J8
RefSeq (mRNA) NM_001619.3 NM_130863.1
RefSeq (protein) NP_001610.2 NP_570933.1
Location (UCSC) Chr 11:
67.03 – 67.05 Mb		 Chr 19:
4.29 – 4.31 Mb
PubMed search [1] [2]

Beta adrenergic receptor kinase (also referred to as βARK or BARK) is a serine/threonine intracellular kinase. It is activated by PKA and its target is the beta adrenergic receptor. It is one method by which the cell will desensitize itself from epinephrine overstimulation.[1][2]

Contents

βARK Activation

Therefore, βARK is a negative feedback enzyme which will prevent over stimulation of the β-adrenergic receptor.[1][2]

Other similar systems

In the rhodopsin system, which regulates rod cell function in the retina, rhodopsin kinase will phosphorylate serine and threonine residues on the rhodopsin receptor. Similarly to the βARK system, the phosphorylated rhodopsin residues will then bind to arrestin resulting in receptor desensitization.

Structure

Protein Structure

The structure of βARK1 consists of a protein of 689 amino acids (79.7 kilodaltons) with a protein kinase catalytic domain that bears greatest sequence similarity to protein kinase C and the cyclic adenosine monophosphate (cyclic AMP)--dependent protein kinase. [3]

Gene structure

The gene spans approximately 23 kilobases and is composed of 21 exons interrupted by 20 introns. Exon sizes range from 52 bases (exon 7) to over 1200 bases (exon 21), intron sizes from 68 bases (intron L) to 10.8 kilobases (intron A). The splice sites for donor and acceptor were in agreement with the canonical GT/AG rule. Functional regions of beta ARK are described with respect to their location within the exon-intron organization of the gene. Primer extension and RNase protection assays suggest a major transcription start site approximately 246 bases upstream of the start ATG. Sequence analysis of the 5'-flanking/promoter region reveals many features characteristic of mammalian housekeeping genes, i.e. the lack of a TATA box, an absent or nonstandard positioned CAAT box, high GC content, and the presence of Sp1-binding sites. The extraordinarily high GC content of the 5'-flanking region (> 80%) helps define this region as a CpG island that may be a principal regulator of beta ARK expression. [4]

Interactions

Beta adrenergic receptor kinase has been shown to interact with PDE6G,[5] GNAQ,[6] Src,[5] PRKCB1[7] and GIT1.[8][9]

See also

References

  1. ^ a b Pippig S, et al. Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors. J Biol Chem. 1993 Feb 15;268(5):3201-8.
  2. ^ a b Pitcher, J, et al. Desensitization of the isolated beta 2-adrenergic receptor by beta-adrenergic receptor kinase, cAMP-dependent protein kinase, and protein kinase C occurs via distinct molecular mechanisms. Biochemistry. 1992 Mar 31;31(12):3193-7.
  3. ^ Benovic, JL, et al. Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science, Vol 246, Issue 4927, 235-240. 1989.
  4. ^ Benovic, JL, et al. Structure of the human gene encoding the beta-adrenergic receptor kinase. J Biol Chem. 1994 May 27;269(21):14924-30
  5. ^ a b Wan, Kah Fei; Sambi Balwinder S, Tate Rothwelle, Waters Catherine, Pyne Nigel J (May. 2003). "The inhibitory gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a signaling unit that regulates p42/p44 mitogen-activated protein kinase by epidermal growth factor". J. Biol. Chem. (United States) 278 (20): 18658–63. doi:10.1074/jbc.M212103200. ISSN 0021-9258. PMID 12624098. 
  6. ^ Day, Peter W; Carman Christopher V, Sterne-Marr Rachel, Benovic Jeffrey L, Wedegaertner Philip B (Aug. 2003). "Differential interaction of GRK2 with members of the G alpha q family". Biochemistry (United States) 42 (30): 9176–84. doi:10.1021/bi034442. ISSN 0006-2960. PMID 12885252. 
  7. ^ Yang, Xing-Long; Zhang Ya-Li, Lai Zhuo-Sheng, Xing Fei-Yue, Liu Yu-Hu (Apr. 2003). "Pleckstrin homology domain of G protein-coupled receptor kinase-2 binds to PKC and affects the activity of PKC kinase". World J. Gastroenterol. (China) 9 (4): 800–3. ISSN 1007-9327. PMID 12679936. 
  8. ^ Premont, R T; Claing A, Vitale N, Perry S J, Lefkowitz R J (Jul. 2000). "The GIT family of ADP-ribosylation factor GTPase-activating proteins. Functional diversity of GIT2 through alternative splicing". J. Biol. Chem. (UNITED STATES) 275 (29): 22373–80. doi:10.1074/jbc.275.29.22373. ISSN 0021-9258. PMID 10896954. 
  9. ^ Premont, R T; Claing A, Vitale N, Freeman J L, Pitcher J A, Patton W A, Moss J, Vaughan M, Lefkowitz R J (Nov. 1998). "beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (24): 14082–7. doi:10.1073/pnas.95.24.14082. ISSN 0027-8424. PMC 24330. PMID 9826657. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24330. 

External links