Evidence map›Paper›PMID 19332778›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity.

Ermanno Puxeddu, Marina Uhart, Chun-Chun Li, Faiyaz Ahmad, Gustavo Pacheco-Rodriguez, Vincent C Manganiello, Joel Moss, Martha Vaughan

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
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  6. Article
  7. Enhancement of β-catenin activity by BIG1 plus BIG2 via Arf activation and cAMP signals.Proceedings of the National Academy of Sciences of the United States of America · 2016
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  9. 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

8 authors at 2 institutions in 1 country.

Ermanno PuxedduTranslational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Marina Uhart
Chun-Chun Li
Faiyaz Ahmad
Gustavo Pacheco-Rodriguez
Vincent C Manganiello
Joel Moss
Martha Vaughan
National Heart Lung and Blood Institute · USNational Institutes of Health · US

Funding

Light Microscopy CoreZICHL006019 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI COMBS, CHRISTIAN · 2009 to 2025
$29.3M
Expression, Structure/function, Regulation, and Roles of PDE3 IsoformsZIAHL002540 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MANGANIELLO, VINCENT · 2009 to 2016
$17.0M
Molecular Characterization and Regulation of GTP-binding ProteinsZIAHL000627 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI VAUGHAN, MARTHA · 2009 to 2016
$8.4M
REGULATION OF GTP-BINDING PROTEINSZ01HL000627 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI VAUGHAN, MARTHA · 1985 to 2008
$4.5M
Phosphodiesterase 3 IsoformsZ01HL002540 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI MANGANIELLO, VINCENT · 1995 to 2008
$4.4M
Intramural NIH HHS
6 · The paper itself

Abstract

ADP-ribosylation factors (ARFs) have crucial roles in vesicular trafficking. Brefeldin A-inhibited guanine nucleotide-exchange proteins (BIG)1 and BIG2 catalyze the activation of class I ARFs by accelerating replacement of bound GDP with GTP. Several additional and differing actions of BIG1 and BIG2 have been described. These include the presence in BIG2 of 3 A kinase-anchoring protein (AKAP) domains, one of which is identical in BIG1. Proteins that contain AKAP sequences act as scaffolds for the assembly of PKA with other enzymes, substrates, and regulators in complexes that constitute molecular machines for the reception, transduction, and integration of signals from cAMP or other sources, which are initiated, propagated, and transmitted by chemical, electrical, or mechanical means. Specific depletion of HeLa cell PDE3A with small interfering RNA significantly decreased membrane-associated BIG1 and BIG2, which by confocal immunofluorescence microscopy were widely dispersed from an initial perinuclear Golgi concentration. Concurrently, activated ARF1-GTP was significantly decreased. Selective inhibition of PDE3A by 1-h incubation of cells with cilostamide similarly decreased membrane-associated BIG1. We suggest that decreasing PDE3A allowed cAMP to accumulate in microdomains where its enzymatic activity limited cAMP concentration. There, cAMP-activated PKA phosphorylated BIG1 and BIG2 (AKAPs for assembly of PKA, PDE3A, and other molecules), which decreased their GEP activity and thereby amounts of activated ARF1-GTP. Thus, PDE3A in these BIG1 and BIG2 AKAP complexes may contribute to the regulation of ARF function via limitation of cAMP effects with spatial and temporal specificity.

Indexed as

8-Bromo Cyclic Adenosine MonophosphateADP-Ribosylation Factor 1Cyclic Nucleotide Phosphodiesterases, Type 3CytosolGuanine Nucleotide Exchange FactorsGuanosine TriphosphateHeLa CellsHumansIntracellular SpacePhosphodiesterase 3 InhibitorsProtein BindingRNA, Small Interfering8-Bromo Cyclic Adenosine MonophosphateADP-Ribosylation Factor 1Cyclic Nucleotide Phosphodiesterases, Type 3Guanine Nucleotide Exchange FactorsGuanosine TriphosphatePhosphodiesterase 3 InhibitorsRNA, Small Interfering

Identifiers

PMID19332778
PMCPMC2662965
OpenAlexW1994203125

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.