A novel subtype of G‐protein‐coupled receptor kinase, GRK7, in teleost cone photoreceptors

Abstract

Two kinds of retinal cDNA fragments (OlGRK-R and -C) encoding the putative G-protein-coupled receptor kinases (GRKs) were isolated from medaka, Oryzias latipes. OlGRK-R appears to be closely related to the rhodopsin kinase (RK) found in the outer segments of mammalian photoreceptors, but the deduced amino acid sequence of OlGRK-C shows less than 50% identity to those of GRKs known to date, suggesting that OlGRK-C is a novel GRK subtype (GRK7). The mRNA of OlGRK-R is detectable in rods, and that of OlGRK-C is found in all four types of cone photoreceptor. The C-terminal of OlGRK-R has a consensus sequence for farnesylation, whereas, surprisingly, OlGRK-C has a consensus sequence for geranylgeranylation. Our result are consistent with the concept that lower vertebrates have rod-and cone-specific opsin kinases.z 1998 Federation of European Biochemical Societies.

G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs)

“…synaptic membranes), their effective concentrations in these compartments could be even higher (74,75,78,97). The behavior of membrane-tethered GRK2 mutants is reminiscent of strict dependence on receptor activation of visual GRK1-and GRK7-dependent phosphorylation of rhodopsin and cone opsins, even though both visual GRKs are constitutively membrane-associated via C-terminal prenylation (50,80). Although GRK1 was shown to phosphorylate many molecules of inactive rhodopsin upon activation of each rhodopsin molecule by light (19,20), this phenomenon could be explained within the framework of the general model that GRK1 activation requires its physical interaction with an active GPCR (8).…”

Abnormality of G-Protein-Coupled Receptor Kinases at Prodromal and Early Stages of Alzheimer's Disease: An Association with Early β-Amyloid Accumulation

“…GRKs belong to a relatively new family of protein kinases, and most of the members were identified in the last decade or so (Hisatomi et al, 1998;Pitcher et al, 1998). Of the seven known GRK isoforms, GRK1 and GRK7 are expressed almost exclusively in retina and GRK4 appears limited to testis, whereas GRK2/3 and GRK5/6 are ubiquitously expressed, including the brain (Pitcher et al, 1998;Kohout and Lefkowitz, 2003).…”

“…In addition, the specificity of GRKs in the regulation of desensitization of a large variety of GPCRs has been a common concern in the field of GRKs (Kohout and Lefkowitz, 2003). The current understanding is that, although there are only seven known GRKs and thousands of GPCRs, desensitization of GPCRs by GRKs is specifically regulated in an agonist-dependent manner (Hisatomi et al, 1998;Pitcher et al, 1998). In addition to GRKs, other protein kinases, such as cAMP-dependent protein kinase and protein kinase C, can directly regulate GPCR desensitization as well (Kohout and Lefkowitz, 2003).…”

“…Because GRKs are primarily responsible for initiating GPCR desensitization (Premont et al, 1995;Hisatomi et al, 1998;Pitcher et al, 1998), we questioned whether subthreshold A␤ has any impact on GRKs. Although regulation of many individual GPCRs by spe- A, Primary mouse brain microglial cultures were pretreated (5 min) with A␤ 1-42 (500 nM), followed by increasing doses of thrombin (24 hr) as indicated (n ϭ 4).…”

The D1 Dopamine Receptor Is Constitutively Phosphorylated by G Protein-Coupled Receptor Kinase 4

“…GRKs are serine/threonine-directed protein kinases composed of seven isoforms divided into three families (Penela et al, 2003). GRK1 and GRK7 compose the rhodopsin kinase/visual family, are expressed exclusively in retina, and participate in desensitization of opsins in rods and cones (Somers and Klein, 1984;Hisatomi et al, 1998;Weiss et al, 1998). GRK2 (␤ARK1) and GRK3 (␤ARK2) were originally identified as regulating the ␤-adrenergic receptor and com- ABBREVIATIONS: GPCR, G protein-coupled receptor; ␤ARK, ␤-adrenergic receptor kinase; GRK, G protein-coupled receptor kinase; DAR, dopamine receptor; HEK, human embryonic kidney; SNP, single-nucleotide polymorphism; GFP, green fluorescent protein; SCH-23390, R-(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; Ro-20-1724, 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one; PVDF, polyvinylidene difluoride; DMEM, Dulbecco's modified essential medium; EBSS, Earle's balanced salt solution; MOPS, 3-(N-morpholino)-propanesulfonic acid; TBST, Tris-buffered saline containing 0.05% Tween 20; WT, wild type; V, vector.…”