Evidence map›Paper›PMID 9122168›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1997

Receptor and G betagamma isoform-specific interactions with G protein-coupled receptor kinases.

Y Daaka, J A Pitcher, M Richardson, R H Stoffel, J D Robishaw, R J Lefkowitz

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
7.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 187 citations in OpenAlex.

  1. Review
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  11. Estrogen Regulation of GRK2 Inactivates Kappa Opioid Receptor Signaling Mediating Analgesia, But Not Aversion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
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  19. Analyzing the roles of multi-functional proteins in cells: The case of arrestins and GRKs.Critical reviews in biochemistry and molecular biology · 2015
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Y DaakaHoward Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
J A Pitcher
M Richardson
R H Stoffel
J D Robishaw
R J Lefkowitz
Duke Medical Center · USHoward Hughes Medical Institute · USDuke University Hospital · US

Funding

PHS HHS 16037PHS HHS 39867
6 · The paper itself

Abstract

The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate and desensitize agonist-occupied GPCRs. GRK2-mediated receptor phosphorylation is preceded by the agonist-dependent membrane association of this enzyme. Previous in vitro studies with purified proteins have suggested that this translocation may be mediated by the recruitment of GRK2 to the plasma membrane by its interaction with the free betagamma subunits of heterotrimeric G proteins (G betagamma). Here we demonstrate that this mechanism operates in intact cells and that specificity is imparted by the selective interaction of discrete pools of G betagamma with receptors and GRKs. Treatment of Cos-7 cells transiently overexpressing GRK2 with a beta-receptor agonist promotes a 3-fold increase in plasma membrane-associated GRK2. This translocation of GRK2 is inhibited by the carboxyl terminus of GRK2, a known G betagamma sequestrant. Furthermore, in cells overexpressing both GRK2 and G beta1 gamma2, activation of lysophosphatidic acid receptors leads to the rapid and transient formation of a GRK/G betagamma complex. That G betagamma specificity exists at the level of the GPCR and the GRK is indicated by the observation that a GRK2/G betagamma complex is formed after agonist occupancy of the lysophosphatidic acid and beta-adrenergic but not thrombin receptors. In contrast to GRK2, GRK3 forms a G betagamma complex after stimulation of all three GPCRs. This G betagamma binding specificity of the GRKs is also reflected at the level of the purified proteins. Thus the GRK2 carboxyl terminus binds G beta1 and G beta2 but not G beta3, while the GRK3 fusion protein binds all three G beta isoforms. 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.

Indexed as

Protein Serine-Threonine KinasesAnimalsbeta-Adrenergic Receptor KinasesCattleCell MembraneCOS CellsCyclic AMP-Dependent Protein KinasesGlutathione TransferaseG-Protein-Coupled Receptor Kinase 3G-Protein-Coupled Receptor Kinase 5GTP-Binding ProteinsIsoproterenolKineticsLysophospholipidsPeptide FragmentsProtein Bindingbeta-Adrenergic Receptor KinasesCyclic AMP-Dependent Protein KinasesGlutathione TransferaseG-Protein-Coupled Receptor Kinase 3G-Protein-Coupled Receptor Kinase 5GTP-Binding ProteinsIsoproterenolLysophospholipidsPeptide FragmentsProtein Serine-Threonine KinasesReceptor Protein-Tyrosine KinasesReceptors, ThrombinRecombinant Fusion ProteinsRecombinant Proteinsthrombin receptor peptide (42-47)

Identifiers

PMID9122168
PMCPMC20061
OpenAlexW2019752875

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.