Evidence map›Paper›PMID 18534983›Full record

ArticleThe Journal of biological chemistry2008

Beta-arrestin scaffolding of phosphatidylinositol 4-phosphate 5-kinase Ialpha promotes agonist-stimulated sequestration of the beta2-adrenergic receptor.

Christopher D Nelson, Jeffery J Kovacs, Kelly N Nobles, Erin J Whalen, Robert J Lefkowitz

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

24 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. β-arrestin-dependent PI(4,5)PProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. β-arrestins and G protein-coupled receptor trafficking.Handbook of experimental pharmacology · 2014
    Review
  13. The very large G protein coupled receptor (Vlgr1) in hair cells.Journal of molecular neuroscience : MN · 2013
    Review
  14. Article
  15. β2-adrenergic receptor and astrocyte glucose metabolism.Journal of molecular neuroscience : MN · 2012
    Article
  16. Review
  17. Article
  18. Review
  19. Functional relevance of biased signaling at the angiotensin II type 1 receptor.Endocrine, metabolic & immune disorders drug targets · 2011
    Review
  20. Review
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

5 authors at 3 institutions in 1 country.

Christopher D NelsonHoward Hughes Medical Institute, Departments of Medicine, Immunology, and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
Jeffery J Kovacs
Kelly N Nobles
Erin J Whalen
Robert J Lefkowitz
Duke University Hospital · USDuke Medical Center · USDuke University · US

Funding

Molecular Regulation of Cardiovascular 7 TM ReceptorsR01HL016037 · NHLBI · DUKE UNIVERSITY · PI ROBERT J LEFKOWITZ · 1985 to 2026
$14.5M
B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular FunctionR01HL070631 · NHLBI · DUKE UNIVERSITY · PI LEFKOWITZ, ROBERT J · 2002 to 2011
$3.5M
TRAINING PROGRAM IN INFLAMMATORY AND IMMUNOLOGICALT32AI007217 · NIAID · DUKE UNIVERSITY · PI PISETSKY, DAVID STEPHEN · 1985 to 2015
$3.3M
MOLECULAR PROPERTIES OF CARDIAC ADRENERGIC RECEPTORSR37HL016037 · NHLBI · DUKE UNIVERSITY · PI LEFKOWITZ, ROBERT J · 1986 to 1995
–
Howard Hughes Medical InstituteNHLBI NIH HHS HL 16037NHLBI NIH HHS HL 70631NHLBI NIH HHS R01 HL016037NHLBI NIH HHS R01 HL070631NIAID NIH HHS T32 AI007217
6 · The paper itself

Abstract

Members of the seven-transmembrane receptor (7TMR) superfamily are sequestered from the plasma membrane following stimulation both to limit cellular responses as well as to initiate novel G protein-independent signaling pathways. The best studied mechanism for 7TMR internalization is via clathrin-coated pits, where clathrin and adaptor protein complex 2 nucleate and polymerize upon encountering the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) to form the outer layer of the clathrin-coated vesicle. Activated receptors are recruited to clathrin-coated pits by beta-arrestins, scaffolding proteins that interact with agonist-occupied 7TMRs as well as adaptor protein complex 2 and clathrin. We report here that following stimulation of the beta2-adrenergic receptor (beta2-AR), a prototypical 7TMR, beta-arrestins bind phosphatidylinositol 4-phosphate 5-kinase (PIP5K) Ialpha, a PIP(2)-producing enzyme. Furthermore, beta-arrestin2 is required to form a complex with PIP5K Ialpha and agonist-occupied beta2-AR, and beta-arrestins synergize with the kinase to produce PIP(2) in response to isoproterenol stimulation. Interestingly, beta-arrestins themselves bind PIP(2), and a beta-arrestin mutant deficient in PIP(2) binding no longer internalizes 7TMRs, fails to interact with PIP5K Ialpha, and is not associated with PIP kinase activity assayed in vitro. However, a chimeric protein in which the core kinase domain of PIP5K Ialpha has been fused to the same beta-arrestin mutant rescues internalization of beta2-ARs. Collectively, these data support a model in which beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization.

Indexed as

EndocytosisAnimalsArrestinsbeta-ArrestinsCell LineCell MembraneClathrinHumansModels, BiologicalMutationPhosphotransferases (Alcohol Group Acceptor)PlasmidsProtein BindingProtein ConformationReceptors, Adrenergic, beta-2Recombinant Fusion Proteins1-phosphatidylinositol-4-phosphate 5-kinaseArrestinsbeta-ArrestinsClathrinPhosphotransferases (Alcohol Group Acceptor)Receptors, Adrenergic, beta-2Recombinant Fusion Proteins

Identifiers

PMID18534983
PMCPMC2475702
OpenAlexW2014517905

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.