Biology:GRK4
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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
- ↑ "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.
- ↑ "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.
- ↑ "GPCR Signaling Regulation: The Role of GRKs and Arrestins". Front Pharmacol 10: 125. 2019. doi:10.3389/fphar.2019.00125. PMID 30837883.
- ↑ "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.
- ↑ "G protein-coupled receptor kinase 4: role in hypertension". Hypertension 65 (6): 1148–1155. 2015. doi:10.1161/HYPERTENSIONAHA.115.05189. PMID 25870190.
- ↑ "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
- "Two isoforms of G protein-coupled receptor kinase 4 identified by molecular cloning". Biochem. Biophys. Res. Commun. 199 (2): 848–54. 1994. doi:10.1006/bbrc.1994.1306. PMID 8135832.
- "G protein-coupled receptor kinase GRK4. Molecular analysis of the four isoforms and ultrastructural localization in spermatozoa and germinal cells". J. Biol. Chem. 272 (15): 10188–95. 1997. doi:10.1074/jbc.272.15.10188. PMID 9092566.
- "Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor". Mol. Endocrinol. 13 (6): 866–78. 1999. doi:10.1210/mend.13.6.0289. PMID 10379886.
- "Determination of bradykinin B2 receptor in vivo phosphorylation sites and their role in receptor function". J. Biol. Chem. 276 (44): 40431–40. 2001. doi:10.1074/jbc.M107024200. PMID 11517230.
- "Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4". Kidney Int. 62 (3): 790–8. 2003. doi:10.1046/j.1523-1755.2002.00525.x. PMID 12164861.
- "Phosphorylation-independent desensitization of GABAB receptor by GRK4". EMBO J. 22 (15): 3816–24. 2003. doi:10.1093/emboj/cdg383. PMID 12881416.
- "Association of G-protein-coupled receptor kinase 4 haplotypes, but not HSD3B1 or PTP1B polymorphisms, with essential hypertension". J. Hypertens. 22 (5): 931–6. 2004. doi:10.1097/00004872-200405000-00014. PMID 15097232.
- "The D1 dopamine receptor is constitutively phosphorylated by G protein-coupled receptor kinase 4". Mol. Pharmacol. 69 (3): 759–69. 2006. doi:10.1124/mol.105.019901. PMID 16338988.
- "The G protein-coupled receptor kinase 4 gene affects blood pressure in young normotensive twins". Am. J. Hypertens. 19 (1): 61–6. 2006. doi:10.1016/j.amjhyper.2005.07.007. PMID 16461192.
- "The G protein-coupled receptor kinase 4 gene modulates stress-induced sodium excretion in black normotensive adolescents". Pediatr. Res. 60 (4): 440–2. 2006. doi:10.1203/01.pdr.0000238250.64591.44. PMID 16940246.
- "Association study of G protein-coupled receptor kinase 4 gene variants with essential hypertension in northern Han Chinese". Ann. Hum. Genet. 70 (Pt 6): 778–83. 2006. doi:10.1111/j.1469-1809.2006.00278.x. PMID 17044852.
- "The elevated blood pressure of human GRK4gamma A142V transgenic mice is not associated with increased ROS production". Am. J. Physiol. Heart Circ. Physiol. 292 (5): H2083–92. 2007. doi:10.1152/ajpheart.00944.2006. PMID 17259440.
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