Rhodopsin kinase

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.{{cite journal | vauthors = Chen CK, Zhang K, Church-Kopish J, Huang W, Zhang H, Chen YJ, Frederick JM, Baehr W | title = Characterization of human GRK7 as a potential cone opsin kinase | journal = Molecular Vision | volume = 7 | pages = 305–13 | date = December 2001 | pmid = 11754336 }} 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.{{cite journal | vauthors = Inglese J, Glickman JF, Lorenz W, Caron MG, Lefkowitz RJ | title = Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase | journal = The Journal of Biological Chemistry | volume = 267 | issue = 3 | pages = 1422–5 | date = January 1992 | doi = 10.1016/S0021-9258(18)45960-1 | pmid = 1730692 | doi-access = free }}{{cite journal | vauthors = Kutuzov MA, Andreeva AV, Bennett N | title = Regulation of the methylation status of G protein-coupled receptor kinase 1 (rhodopsin kinase) | journal = Cellular Signalling | volume = 24 | issue = 12 | pages = 2259–67 | date = December 2012 | pmid = 22846544 | doi = 10.1016/j.cellsig.2012.07.020 }}

Arrestin-1 bound to rhodopsin prevents rhodopsin activation of the transducin protein to turn off photo-transduction completely.{{cite journal | vauthors = Sakurai K, Chen J, Khani SC, Kefalov VJ | title = Regulation of mammalian cone phototransduction by recoverin and rhodopsin kinase | journal = The Journal of Biological Chemistry | volume = 290 | issue = 14 | pages = 9239–50 | date = April 2015 | pmid = 25673692 | pmc = 4423708 | doi = 10.1074/jbc.M115.639591 | doi-access = free }}{{cite journal | vauthors = Sakurai K, Young JE, Kefalov VJ, Khani SC | title = Variation in rhodopsin kinase expression alters the dim flash response shut off and the light adaptation in rod photoreceptors | journal = Investigative Ophthalmology & Visual Science | volume = 52 | issue = 9 | pages = 6793–800 | date = August 2011 | pmid = 21474765 | doi = 10.1167/iovs.11-7158 | pmc=3176010}}

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.{{cite journal | vauthors = Chen CK, Inglese J, Lefkowitz RJ, Hurley JB | title = Ca(2+)-dependent interaction of recoverin with rhodopsin kinase | journal = The Journal of Biological Chemistry | volume = 270 | issue = 30 | pages = 18060–6 | date = July 1995 | pmid = 7629115 | doi=10.1074/jbc.270.30.18060| doi-access = free }}{{cite journal | vauthors = Komolov KE, Senin II, Kovaleva NA, Christoph MP, Churumova VA, Grigoriev II, Akhtar M, Philippov PP, Koch KW | title = Mechanism of rhodopsin kinase regulation by recoverin | journal = Journal of Neurochemistry | volume = 110 | issue = 1 | pages = 72–9 | date = July 2009 | pmid = 19457073 | doi = 10.1111/j.1471-4159.2009.06118.x | s2cid = 205620698 | doi-access = free }}

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.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.

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.{{cite journal | vauthors = Teke MY, Citirik M, Kabacam S, Demircan S, Alikasifoglu M | title = A novel missense mutation of the GRK1 gene in Oguchi disease | journal = Molecular Medicine Reports | volume = 14 | issue = 4 | pages = 3129–33 | date = October 2016 | pmid = 27511724 | doi = 10.3892/mmr.2016.5620 | pmc = 5042745 | doi-access = free }}

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.{{cite journal | vauthors = Choi S, Hao W, Chen CK, Simon MI | title = Gene expression profiles of light-induced apoptosis in arrestin/rhodopsin kinase-deficient mouse retinas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 23 | pages = 13096–101 | date = November 2001 | pmid = 11687607 | doi = 10.1073/pnas.201417498 | pmc = 60830 | bibcode = 2001PNAS...9813096C | doi-access = free }} When photoreceptors cells die, they will be detached from the retina and result in retinal degeneration.{{cite journal | vauthors = Murakami Y, Notomi S, Hisatomi T, Nakazawa T, Ishibashi T, Miller JW, Vavvas DG | title = Photoreceptor cell death and rescue in retinal detachment and degenerations | journal = Progress in Retinal and Eye Research | volume = 37 | issue = 2013 | pages = 114–40 | date = November 2013 | pmid = 23994436 | doi = 10.1016/j.preteyeres.2013.08.001 | pmc = 3871865 }}

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

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{{Eye proteins}}

{{Serine/threonine-specific protein kinases}}

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Category:EC 2.7.11