Protein kinases that phosphorylate activated G protein‐coupled receptors

@article{Premont1995ProteinKT,
  title={Protein kinases that phosphorylate activated G protein‐coupled receptors},
  author={R T Premont and James Inglese and R J Lefkowitz},
  journal={The FASEB Journal},
  year={1995},
  volume={9},
  pages={175 - 182}
}
G protein‐coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that specifically recognize agonist‐occupied, activated G protein‐coupled receptor proteins as substrates. Phosphorylation of an activated receptor by a GRK terminates signaling by that receptor, by initiating the uncoupling of the receptor from heterotrimeric G proteins. Six distinct mammalian GRKs are known, which differ in tissue distribution and in regulatory properties. The intracellular localization… 
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The results suggest that PKC might play an important role in modulating the ability of GRK5 to regulate receptor signaling and that GRK phosphorylation by PKC may serve as a disparate mechanism for regulating GRK activity.
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TLDR
The roles of regulatory molecules as modulators of GPCR signalling are discussed, including members of the arrestin family, which bind to the phosphorylated and activated GPCRs and cause desensitization by precluding further interactions of the G PCRs and G‐proteins.
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TLDR
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TLDR
This study provides a direct demonstration of a role for G betagamma in mediating the agonist-stimulated translocation of GRK2 and GRK3 in an intact cellular system and demonstrates isoform specificity in the interaction of these components.
Regulation of G Protein-coupled Receptor Kinases by Calmodulin and Localization of the Calmodulin Binding Domain*
TLDR
It is demonstrated that calmodulin, another mediator of calcium signaling, is a potent inhibitor of GRK activity with a selectivity for GRK5 (IC50 ∼50 nm) > GRK6 ≫ GRK2 ( IC50 ∼2 μm) ≬ GRK1.
Structure-Function Analysis of G Protein-coupled Receptor Kinase-5
TLDR
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References

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TLDR
It has been proposed that the designation GRK be adopted with numbering pro-ceeding in the chronological order of the kinase’s (4) GRKs, for members of this kinase gene family for which the functional roles remain completely unknown.
Phospholipid-stimulated autophosphorylation activates the G protein-coupled receptor kinase GRK5.
TLDR
Results suggest that phospholipid-stimulated autophosphorylation may represent a novel mechanism for membrane association and regulation of GRK5 activity.
Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases
TLDR
The results indicate that rhodopsin kinase and β ARK both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function.
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  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
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TLDR
The isolation of a cDNA that encodes a 590-amino acid protein kinase, termed GRK5, which was able to phosphorylate rhodopsin in a light-dependent manner and represents a member of the GRK family that likely has a unique physiological role.
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TLDR
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TLDR
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