Biology:GRK4

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the GRK4 gene in humans.[1]

This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most similar to GRK5 and GRK6.[2]

G protein-coupled receptor kinases phosphorylate activated G protein-coupled receptors, which promotes the binding of an arrestin protein to the receptor. Arrestin binding to a phosphorylated, active receptor prevents receptor stimulation of heterotrimeric G protein transducer proteins, blocking their cellular signaling and resulting in receptor desensitization. Moreover Arrestin binding to a phosphorylated, active receptor also enables receptor signaling through arrestin partner proteins. Consequently the GRK/arrestin system serves as a signaling switch for G protein-coupled receptors.[3]

GRK4 is most highly expressed in the testes, with lower amounts found in the brain, kidney and other tissues. It exists in four alternatively-spliced variants.[4]

Polymorphisms in the GRK4 gene have been linked to both genetic and acquired hypertension, partly acting through kidney dopamine receptors.[5][6]

References

  1. "A novel G protein-coupled receptor kinase gene cloned from 4p16.3". Hum Mol Genet 1 (9): 697–703. Jun 1993. doi:10.1093/hmg/1.9.697. PMID 1338872. 
  2. "Protein kinases that phosphorylate activated G protein-coupled receptors". FASEB J 9 (2): 175–182. 1995. doi:10.1096/fasebj.9.2.7781920. PMID 7781920. 
  3. "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol 10: 125. 2019. doi:10.3389/fphar.2019.00125. PMID 30837883. 
  4. "Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants". J. Biol. Chem. 271 (11): 6403–10. 1996. doi:10.1074/jbc.271.11.6403. PMID 8626439. 
  5. "G protein-coupled receptor kinase 4: role in hypertension". Hypertension 65 (6): 1148–1155. 2015. doi:10.1161/HYPERTENSIONAHA.115.05189. PMID 25870190. 
  6. "Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis". Clin Interv Aging 11: 17–27. 2016. doi:10.2147/CIA.S94510. PMID 26730182. 

Further reading