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

@article{Rankin2006TheDD,
  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},
  year={2006},
  volume={69},
  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… 
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TLDR
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
TLDR
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.

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

TLDR
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.

Characterization of G protein-coupled receptor kinase 4 and measuring its constitutive activity in vivo.

Cytoplasmic tail of D1 dopaminergic receptor differentially regulates desensitization and phosphorylation by G protein-coupled receptor kinase 2 and 3.

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

TLDR
GRK5/6 effectively phosphorylation of the inactive β2-adrenergic receptor enhanced its interactions with arrestins, suggesting that not only agonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-receptor complex and thereby G protein-independent signaling.

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

TLDR
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.

G protein-coupled receptor kinases: more than just kinases and not only for GPCRs.

Regulation of the Dopamine D1-D2 Receptor Heterooligomer

TLDR
The results indicated that desensitization of the D1-D2 receptor heteromer mediated calcium signal can occur by agonist occupancy even without activation and is regulated by two distinct functions of GRK2.
...

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