Rhodopsin kinase (original) (raw)

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Protein-coding gene in the species Homo sapiens

Rhodopsin kinase (EC 2.7.11.14, rod opsin kinase, G-protein-coupled receptor kinase 1, GPCR kinase 1, GRK1, opsin kinase, opsin kinase (phosphorylating), rhodopsin kinase (phosphorylating), RK, STK14) is a serine/threonine-specific protein kinase involved in phototransduction.[1][2][3][4][5][6][7][8] This enzyme catalyses the following chemical reaction:

ATP + rhodopsin ⇌ {\displaystyle \rightleftharpoons } ADP + phospho-rhodopsin

Mutations in rhodopsin kinase are associated with a form of night blindness called Oguchi disease.[9]

Function and mechanism of action

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Rhodopsin kinase is a member of the family of G protein-coupled receptor kinases, and is officially named G protein-coupled receptor kinase 1, or GRK1. Rhodopsin kinase is found primarily in mammalian retinal rod cells, where it phosphorylates light-activated rhodopsin, a member of the family of G protein-coupled receptors that recognizes light. Phosphorylated, light-activated rhodopsin binds to the protein arrestin to terminate the light-activated signaling cascade. The related GRK7, also known as cone opsin kinase, serves a similar function in retinal cone cells subserving high-acuity color vision in the fovea.[10] The post-translational modification of GRK1 by farnesylation and α-carboxyl methylation is important for regulating the ability of the enzyme to recognize rhodopsin in rod outer segment disk membranes.[11][12]

Arrestin-1 bound to rhodopsin prevents rhodopsin activation of the transducin protein to turn off photo-transduction completely.[13][14]

Rhodopsin kinase is inhibited by the calcium-binding protein recoverin in a graded manner that maintains rhodopsin sensitivity to light despite large changes in ambient light conditions. That is, in retinas exposed to only dim light, calcium levels are high in retinal rod cells and recoverin is bound to and inhibits rhodopsin kinase, leaving rhodopsin exquisitely sensitive to photons to mediate low-light, low-acuity vision; in bright light, rod cell calcium levels are low so recoverin cannot bind or inhibit rhodopsin kinase, resulting in greater rhodopsin kinase/arrestin inhibition of rhodopsin signaling at baseline to preserve visual sensitivity.[15][16]

According to a proposed model, the N-terminus of rhodopsin kinase is involved in its own activation. It's suggested that an activated rhodopsin binds to the N-terminus, which is also involved in the stabilization of the kinase domain to induce an active conformation.[17]

Mutation in rhodopsin kinase can result in diseases such as Oguchi disease and retinal degeneration. Oguchi disease is a form of congenital stationary night blindness (CSNB). Congenital stationary night blindness is caused by the inability to send a signal from outer retina to the inner retina by signaling molecules. Oguchi disease is a genetic disorder so an individual can be inherited from his or her parents. Genes that are responsible for Oguchi disease are SAG (which encodes arrestin) and GRK1 genes. Rhodopsin kinase is encoded from the GRK1 gene, so a mutation in GRK1 can result in Oguchi disease.[18]

Retinal degeneration is a form of the retinal disease caused by the death of photoreceptor cells that present in the back of the eye, retina. Rhodopsin kinase directly participates in the rhodopsin to activate the visual phototransduction. Studies have shown that lack of rhodopsin kinase will result in photoreceptor cell death.[19] When photoreceptors cells die, they will be detached from the retina and result in retinal degeneration.[20]

• Rhodopsin
• Visual phototransduction
• G-protein coupled receptor kinases
• GRK2

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6. ^ Cha K, Bruel C, Inglese J, Khorana HG (September 1997). "Rhodopsin kinase: expression in baculovirus-infected insect cells, and characterization of post-translational modifications". Proceedings of the National Academy of Sciences of the United States of America. 94 (20): 10577–82. Bibcode:1997PNAS...9410577C. doi:10.1073/pnas.94.20.10577. PMC 23407. PMID 9380677.
7. ^ Khani SC, Abitbol M, Yamamoto S, Maravic-Magovcevic I, Dryja TP (August 1996). "Characterization and chromosomal localization of the gene for human rhodopsin kinase". Genomics. 35 (3): 571–6. doi:10.1006/geno.1996.0399. PMID 8812493.
8. ^ Willets JM, Challiss RA, Nahorski SR (December 2003). "Non-visual GRKs: are we seeing the whole picture?". Trends in Pharmacological Sciences. 24 (12): 626–33. doi:10.1016/j.tips.2003.10.003. PMID 14654303.
9. ^ Yamamoto S, Sippel KC, Berson EL, Dryja TP (February 1997). "Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness". Nature Genetics. 15 (2): 175–8. doi:10.1038/ng0297-175. PMID 9020843. S2CID 9317102.
10. ^ Chen CK, Zhang K, Church-Kopish J, Huang W, Zhang H, Chen YJ, Frederick JM, Baehr W (December 2001). "Characterization of human GRK7 as a potential cone opsin kinase". Molecular Vision. 7: 305–13. PMID 11754336.
11. ^ Inglese J, Glickman JF, Lorenz W, Caron MG, Lefkowitz RJ (January 1992). "Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase". The Journal of Biological Chemistry. 267 (3): 1422–5. doi:10.1016/S0021-9258(18)45960-1. PMID 1730692.
12. ^ Kutuzov MA, Andreeva AV, Bennett N (December 2012). "Regulation of the methylation status of G protein-coupled receptor kinase 1 (rhodopsin kinase)". Cellular Signalling. 24 (12): 2259–67. doi:10.1016/j.cellsig.2012.07.020. PMID 22846544.
13. ^ Sakurai K, Chen J, Khani SC, Kefalov VJ (April 2015). "Regulation of mammalian cone phototransduction by recoverin and rhodopsin kinase". The Journal of Biological Chemistry. 290 (14): 9239–50. doi:10.1074/jbc.M115.639591. PMC 4423708. PMID 25673692.
14. ^ Sakurai K, Young JE, Kefalov VJ, Khani SC (August 2011). "Variation in rhodopsin kinase expression alters the dim flash response shut off and the light adaptation in rod photoreceptors". Investigative Ophthalmology & Visual Science. 52 (9): 6793–800. doi:10.1167/iovs.11-7158. PMC 3176010. PMID 21474765.
15. ^ Chen CK, Inglese J, Lefkowitz RJ, Hurley JB (July 1995). "Ca(2+)-dependent interaction of recoverin with rhodopsin kinase". The Journal of Biological Chemistry. 270 (30): 18060–6. doi:10.1074/jbc.270.30.18060. PMID 7629115.
16. ^ Komolov KE, Senin II, Kovaleva NA, Christoph MP, Churumova VA, Grigoriev II, Akhtar M, Philippov PP, Koch KW (July 2009). "Mechanism of rhodopsin kinase regulation by recoverin". Journal of Neurochemistry. 110 (1): 72–9. doi:10.1111/j.1471-4159.2009.06118.x. PMID 19457073. S2CID 205620698.
17. ^ Orban, Tivadar, et al. “Substrate-Induced Changes in the Dynamics of Rhodopsin Kinase (G Protein-Coupled Receptor Kinase 1).” Biochemistry, vol. 51, no. 16, 2012, pp. 3404–3411.
18. ^ Teke MY, Citirik M, Kabacam S, Demircan S, Alikasifoglu M (October 2016). "A novel missense mutation of the GRK1 gene in Oguchi disease". Molecular Medicine Reports. 14 (4): 3129–33. doi:10.3892/mmr.2016.5620. PMC 5042745. PMID 27511724.
19. ^ Choi S, Hao W, Chen CK, Simon MI (November 2001). "Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas". Proceedings of the National Academy of Sciences of the United States of America. 98 (23): 13096–101. Bibcode:2001PNAS...9813096C. doi:10.1073/pnas.201417498. PMC 60830. PMID 11687607.
20. ^ Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG (November 2013). "Photoreceptor cell death and rescue in retinal detachment and degenerations". Progress in Retinal and Eye Research. 37 (2013): 114–40. doi:10.1016/j.preteyeres.2013.08.001. PMC 3871865. PMID 23994436.

• Rhodopsin+kinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)