GRK1,4,7 phosphorylate MII to p-MII

Stable Identifier
R-HSA-2581474
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
GRK1 phosphorylates MII to p-S334,S338,S343-MII
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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
8626439 Characterization of the G protein-coupled receptor kinase GRK4. Identification of four splice variants

Premont, RT, Macrae, AD, Stoffel, RH, Chung, N, Pitcher, JA, Ambrose, C, Inglese, J, MacDonald, ME, Lefkowitz, RJ

J. Biol. Chem. 1996
11754336 Characterization of human GRK7 as a potential cone opsin kinase

Chen, CK, Zhang, K, Church-Kopish, J, Huang, W, Zhang, H, Chen, YJ, Frederick, JM, Baehr, W

Mol. Vis. 2001
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

Burns, ME, Pugh, EN

Physiology (Bethesda) 2010
15946941 Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates their enzymatic activities

Horner, TJ, Osawa, S, Schaller, MD, Weiss, ER

J. Biol. Chem. 2005
3164688 The sequence of human retinal S-antigen reveals similarities with alpha-transducin.

Yamaki, K, Tsuda, M, Shinohara, T

FEBS Lett 1988
8812493 Characterization and chromosomal localization of the gene for human rhodopsin kinase

Khani, SC, Abitbol, M, Yamamoto, S, Maravic-Magovcevic, I, Dryja, TP

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

Murakami, A, Yajima, T, Inana, G

Biochem. Biophys. Res. Commun. 1992
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Catalyst Activity
Title
rhodopsin kinase activity of GRK1,4,7 [photoreceptor disc membrane]
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This event is regulated
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