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

  title={The D1 Dopamine Receptor Is Constitutively Phosphorylated by G Protein-Coupled Receptor Kinase 4},
  author={Michele L. Rankin and Paul S. Marinec and David M. Cabrera and Zheng Wang and Pedro A. Jose and David R. Sibley},
  journal={Molecular Pharmacology},
  pages={759 - 769}
G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate agonist-activated GPCRs, initiating their homologous desensitization. In this article, we present data showing that GRK4 constitutively phosphorylates the D1 receptor in the absence of agonist activation. This constitutive phosphorylation is mediated exclusively by the α isoform of GRK4; the β, γ, and δ isoforms are ineffective in this regard. Mutational analysis reveals that the constitutive phosphorylation mediated by GRK4α is… 

G Protein-coupled Receptor Kinase-mediated Phosphorylation Regulates Post-endocytic Trafficking of the D2 Dopamine Receptor*

A novel role for GRK-mediated phosphorylation in regulating the post-endocytic trafficking of a G protein-coupled receptor is revealed.

Novel Features of G Protein-Coupled Receptor Kinase 4

  • K. Neve
  • Biology
    Molecular Pharmacology
  • 2006
It is demonstrated that under some conditions, at least, the G protein-coupled receptor kinase GRK4 does not display a preference for the agonist-occupied D1 dopamine receptor.

G protein-coupled receptor kinases as regulators of dopamine receptor functions.

G Protein-Coupled Receptor Kinase 2 (GRK2) and 5 (GRK5) Exhibit Selective Phosphorylation of the Neurotensin Receptor in Vitro

In vitro phosphorylation of the class A GPCR neurotensin receptor 1 (NTSR1) by GRKs is reported on under defined experimental conditions afforded by nanodisc technology and it is revealed that GRK2 and GRK5 target different residues located on the intracellular receptor elements.

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

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G Protein-coupled Receptor Kinase 4 (GRK4) Regulates the Phosphorylation and Function of the Dopamine D3 Receptor*

G protein-coupled receptor kinase 4, specifically the GRK4-γ and GRK 4-α isoforms, phosphorylates the D3 receptor and is crucial for its signaling in human proximal tubule cells.

Regulation of the Dopamine D1-D2 Receptor Heterooligomer

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Identification of the G Protein-coupled Receptor Kinase Phosphorylation Sites in the Human β2-Adrenergic Receptor*

The location of multiple GRK2 and GRK5 phosphoacceptor sites at the extreme carboxyl terminus of the β2AR is highly reminiscent of GRK1-mediated phosphorylation of rhodopsin.

Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling.

Findings indicate distinct functional capabilities of beta-arrestins bound to receptors phosphorylated by different classes of GRKs, which are related to receptor recruitment, recruitment, and receptor endocytosis.

Regulation of dopamine D(1) receptor trafficking by protein kinase A-dependent phosphorylation.

It is concluded that protein kinase A-dependent phosphorylation of the D(1) receptor on Thr268 regulates a late step in the sorting of the receptor to the perinuclear region of the cell, but that phosphorylations of Thr268 is not required for receptor sequestration or maximal desensitization of cyclic AMP accumulation.

The Role of Phosphorylation in D1 Dopamine Receptor Desensitization

The data suggest a model in which arrestin directly associates with the activated 3rd cytoplasmic domain in an agonist-dependent fashion; however, under basal conditions, this is sterically prevented by the carboxyl terminus of the receptor.

The role of phosphorylation/dephosphorylation in agonist-induced desensitization of D1 dopamine receptor function: evidence for a novel pathway for receptor dephosphorylation.

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Regulation of D(1) dopamine receptors with mutations of protein kinase phosphorylation sites: attenuation of the rate of agonist-induced desensitization.

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Bimodal Regulation of the Human H1 Histamine Receptor by G Protein-coupled Receptor Kinase 2*

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G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins.

GRK-mediated phosphorylation and arrestin binding are not only involved in the functional uncoupling of GPCRs but they are also intimately involved in promoting GPCR sequestration and as such likely play an important role in mediating the subsequent resensitization of G PCRs.

Silencing of the Constitutive Activity of the Dopamine D1B Receptor

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