Mechanism of rhodopsin kinase activation

Palczewski, Krzysztof; Buczyłko, Janina; Kaplan, Michael W.; Polans, Arthur S.; Crabb, John W.

doi:10.1016/s0021-9258(18)98787-9

Cited by 299 publications

(59 citation statements)

References 47 publications

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“…In addition, affinity-purified anti-P-Rho334 antibody was subjected to Western blot analysis to endoproteinase-, Asp-N, treated (enzyme:substrate = 1:1000 for overnight at room temperature) or untreated P-Rho. The endoproteinase AspN cleaves off C-terminal 19 amino acids containing all possible sites of phosphorylation (Palczewski et al 1991). The pellet was dissolved in 50 μl SDS-PAGE sample buffer and analyzed with SDS-PAGE using 12.5% gel.…”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical Detection of Phosphorylated Rhodopsin in Light-exposed Retina of Living Mouse with In Vivo Cryotechnique

Terada

Ohno

Ohguro

et al. 2006

J Histochem Cytochem.

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The purpose of this study is to analyze the time-dependent molecular states of rhodopsin (Rho) phosphorylation in the specimens originating from eyeballs cryoimmobilized in situ in living animals. Whole eyeballs of living mice under various dark- and light-exposure conditions were quickly frozen using the in vivo cryotechnique with isopentane-propane cryogen cooled down in liquid nitrogen (-196C). The frozen whole-mount eyeballs were freeze substituted in acetone containing paraformaldehyde and embedded in paraffin wax. Deparaffinized sections were immunostained with anti-phosphorylated (334)Ser Rho (P-Rho334) antibody. Immunoreactivity of P-Rho334 was specifically recognized in the outer segments of mouse retinas exposed to daylight. In the 12-h dark-adapted retinas, P-Rho334 immunoreactivity was completely eliminated. Moreover, in other retinas dark adapted for 12 or 36 hr and then exposed under the safety red light for 2 min, it was still barely recognized. Even in the eyeballs exposed to strong visible light for 10 sec, it was not detected. However, after 30, 60, and 180 sec of visible light exposure, P-Rho334 immunoreactivity was definitely recovered, similar to that under daylight condition. This is a new immunohistochemical approach to visualize the time-dependent Rho phosphorylation of living mice using the in vivo cryotechnique, in which changes could be detected within seconds following exposure to light.

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Section: Methodsmentioning

confidence: 99%

Immunohistochemical Detection of Phosphorylated Rhodopsin in Light-exposed Retina of Living Mouse with In Vivo Cryotechnique

Terada

Ohno

Ohguro

et al. 2006

J Histochem Cytochem.

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“…The phosphates that promote arrestin binding are, in most cases, attached by GRKs, although there are reports that phosphates attached by other kinases can also "attract" arrestins [131,132]. Usually, GRKs selectively phosphorylate active GPCRs, likely because GRKs are activated by binding to active receptors [133][134][135]. The idea that GRK activation appears to require its physical interaction with an active receptor is supported by structural studies [70,71].…”

Section: Receptor-attached Phosphates In Arrestin Bindingmentioning

confidence: 99%

Receptor-Arrestin Interactions: The GPCR Perspective

et al. 2021

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Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin–GPCR interactions has been extensively studied and discussed from the “arrestin perspective”, focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the “receptor perspective”, focusing on the receptor elements involved in arrestin binding and emphasizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter’s transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.

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“…GRKs have been shown to be allosterically activated via binding to active GPCRs ( Palczewski et al, 1991 ; Chen et al, 1993 ; Huang and Tesmer, 2011 ). This binding mechanism has not been fully understood yet, but possibly features the insertion of a N-terminal α-helix into the cytoplasmic cavity of the GPCR.…”

Section: Arrestins and Grks Facilitate Targeted Downstream Functions For Hundreds Of Gpcrsmentioning

confidence: 99%

“…In a cellular context, GRK-binding leads to the phosphorylation of active GPCRs at their intracellular sites. Notably, GRKs have also been shown to phosphorylate non-GPCR substrates ( Palczewski et al, 1991 ; McCarthy and Akhtar, 2002 ), albeit with higher efficiency in the presence of active GPCRs. Thus, GRKs most likely also regulate other cellular processes in a phosphorylation-dependent manner, but in this review, we will predominantly discuss their impact on GPCR signaling.…”

Section: Arrestins and Grks Facilitate Targeted Downstream Functions For Hundreds Of Gpcrsmentioning

confidence: 99%

“…If we now carefully consider these possibilities, we can envision that a given GPCR interacts with a GRK and depending on their relative complex geometry, this event will add the first phosphate group to the receptor stretch which is closest to the active site of the GRK. Early experimental evidence for such a scenario was demonstrated for rhodopsin 30 years ago when even exogenous peptides in the vicinity of GRK1 were phosphorylated ( Palczewski et al, 1991 ). This initial phosphorylation could have local structural consequences and allow or disallow certain residues of the receptor to be phosphorylated next.…”

Section: How the “Barcode” Hypothesis Can Be Interpreted Structurally: Intrinsically Disordered Regionsmentioning

confidence: 99%

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Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

Matthees

Haider

Hoffmann

et al. 2021

Front. Cell Dev. Biol.

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G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors and their signal transduction is tightly regulated by GPCR kinases (GRKs) and β-arrestins. In this review, we discuss novel aspects of the regulatory GRK/β-arrestin system. Therefore, we briefly revise the origin of the “barcode” hypothesis for GPCR/β-arrestin interactions, which states that β-arrestins recognize different receptor phosphorylation states to induce specific functions. We emphasize two important parameters which may influence resulting GPCR phosphorylation patterns: (A) direct GPCR–GRK interactions and (B) tissue-specific expression and availability of GRKs and β-arrestins. In most studies that focus on the molecular mechanisms of GPCR regulation, these expression profiles are underappreciated. Hence we analyzed expression data for GRKs and β-arrestins in 61 tissues annotated in the Human Protein Atlas. We present our analysis in the context of pathophysiological dysregulation of the GPCR/GRK/β-arrestin system. This tissue-specific point of view might be the key to unraveling the individual impact of different GRK isoforms on GPCR regulation.

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Mechanism of rhodopsin kinase activation

Cited by 299 publications

References 47 publications

Immunohistochemical Detection of Phosphorylated Rhodopsin in Light-exposed Retina of Living Mouse with In Vivo Cryotechnique

Immunohistochemical Detection of Phosphorylated Rhodopsin in Light-exposed Retina of Living Mouse with In Vivo Cryotechnique

Receptor-Arrestin Interactions: The GPCR Perspective

Differential Regulation of GPCRs—Are GRK Expression Levels the Key?

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