Reactome | GRK1,4,7 phosphorylate MII to p-MII

GRK1,4,7 phosphorylate MII to p-MII

Stable Identifier

R-HSA-2581474

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, photoreceptor disc membrane

Synonyms

GRK1 phosphorylates MII to p-S334,S338,S343-MII

ReviewStatus

5/5

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Activated rhodopsin (MII aka R*) must be deactivated to terminate the single photon response. Deactivation begins during the rising phase of the single photon response after MII binds rhodopsin kinase (GRK1), a serine/threonine protein kinase (Khani et al. 1996). GRK1 is activated by MII whereupon it phosphorylates MII at multiple serine and threonine sites on its C terminus. There are six serine and threonine residues that can be phosphorylated. Increasing phosphorylation progressively reduces the rate at which MII can activate transducin but full quenching requires the binding of arrestin (S-antigen or SAG, Yamaki et al. 1988) which binds to and sterically caps MII (Burns & Pugh 2010, Korenbrot 2012). GRK4-alpha (isoform 1) and GRK7 are also able to phosphorylate rhodopsin thereby deactivating it (Premont et al. 1996, Chen et al. 2001, Horner et al. 2005, Osawa et al. 2008).

A substantial fraction of rhodopsin kinase (GRK1) is bound to recoverin (RCVRN) in darkness, when internal Ca2+ levels are high. RCVRN is an EF-hand protein (Murakami et al. 1992) that functions as a myristoyl switch. With Ca2+ bound, the myristoyl group is exposed to attach RCVRN to the membrane. When Ca2+ levels drop with light exposure, Ca2+ dissociates from RCVRN and GRK1 is released. Higher levels of free GRK1 accelerate the phosphorylation and shutoff of photoexcited rhodopsin (MII).

Certain mutations in GRK1 cause Oguchi type 2 disease, a rare, recessive form of congenital stationary night blindness (https://sph.uth.edu/retnet/).

Literature References

PubMed ID	Title	Journal	Year
11754336	Characterization of human GRK7 as a potential cone opsin kinase Chen, YJ, Chen, CK, Frederick, JM, Huang, W, Zhang, K, Zhang, H, Baehr, W, Church-Kopish, J	Mol. Vis.	2001
8626439	Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants Premont, RT, MacDonald, ME, Lefkowitz, RJ, Pitcher, JA, Stoffel, RH, Inglese, J, Ambrose, C, Chung, N, Macrae, AD	J. Biol. Chem.	1996
22658984	Speed, sensitivity, and stability of the light response in rod and cone photoreceptors: facts and models Korenbrot, JI	Prog Retin Eye Res	2012
20430952	Lessons from photoreceptors: turning off G-protein signaling in living cells Pugh, EN, Burns, ME	Physiology (Bethesda)	2010
15946941	Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities Osawa, S, Schaller, MD, Weiss, ER, Horner, TJ	J. Biol. Chem.	2005
3164688	The sequence of human retinal S-antigen reveals similarities with alpha-transducin. Shinohara, T, Tsuda, M, Yamaki, K	FEBS Lett	1988
8812493	Characterization and chromosomal localization of the gene for human rhodopsin kinase Abitbol, M, Khani, SC, Dryja, TP, Yamamoto, S, Maravic-Magovcevic, I	Genomics	1996
18803695	Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by light Osawa, S, Jo, R, Weiss, ER	J. Neurochem.	2008
1387789	Isolation of human retinal genes: recoverin cDNA and gene Inana, G, Murakami, A, Yajima, T	Biochem. Biophys. Res. Commun.	1992