Evidence map›Paper›PMID 22366721›Full record

ArticleNature chemical biology2012

Regulation of nuclear PKA revealed by spatiotemporal manipulation of cyclic AMP.

Vedangi Sample, Lisa M DiPilato, Jason H Yang, Qiang Ni, Jeffrey J Saucerman, Jin Zhang

Erratum issuedAbstract read
In one paragraph

Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

78 citing papers in PubMed, 131 citations in OpenAlex.

  1. Article
  2. Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Location bias: A "Hidden Variable" in GPCR pharmacology.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    Review
  7. Article
  8. Advances inJournal of fungi (Basel, Switzerland) · 2023
    Review
  9. Article
  10. Article
  11. Soluble cyclase-mediated nuclear cAMP synthesis is sufficient for cell proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Vedangi SampleDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Lisa M DiPilato
Jason H Yang
Qiang Ni
Jeffrey J Saucerman
Jin Zhang
Johns Hopkins University · USUniversity of Virginia · USJohns Hopkins Medicine · US

Funding

JHU-UMD Diabetes Research CenterP30DK079637 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI WONDISFORD, FREDRIC E. · 2013 to 2017
$9.7M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
BIOTECHNOLOGY TRAINING PROGRAMT32GM008715 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LAURIE, GORDON WILLIAM · 2000 to 2019
$6.6M
Creating a Genetically Encodable Nano-Compass to Navigate in Molecular NetworksDP1OD006419 · OD · JOHNS HOPKINS UNIVERSITY · PI ZHANG, JIN · 2009 to 2011
$2.5M
Quantitative analysis of cAMP compartmentation in heartR01HL094476 · NHLBI · UNIVERSITY OF VIRGINIA · PI SAUCERMAN, JEFFREY J. · 2009 to 2013
$1.8M
Compartmentation of cAMP and Its Coupling to EpacF31DK074381 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DIPILATO, LISA M. · 2006 to 2008
$136k
NHLBI NIH HHS R01 HL094476NIDDK NIH HHS F31 DK074381NIDDK NIH HHS P30 DK079637NIDDK NIH HHS R01 DK073368NIGMS NIH HHS GM08715NIGMS NIH HHS T32 GM008715NIH HHS DP1 OD006419
6 · The paper itself

Abstract

Understanding how specific cyclic AMP (cAMP) signals are organized and relayed to their effectors in different compartments of the cell to achieve functional specificity requires molecular tools that allow precise manipulation of cAMP in these compartments. Here we characterize a new method using bicarbonate-activatable and genetically targetable soluble adenylyl cyclase to control the location, kinetics and magnitude of the cAMP signal. Using this live-cell cAMP manipulation in conjunction with fluorescence imaging and mechanistic modeling, we uncovered the activation of a resident pool of protein kinase A (PKA) holoenzyme in the nuclei of HEK-293 cells, modifying the existing dogma of cAMP-PKA signaling in the nucleus. Furthermore, we show that phosphodiesterases and A-kinase anchoring proteins (AKAPs) are critical in shaping nuclear PKA responses. Collectively, our data suggest a new model in which AKAP-localized phosphodiesterases tune an activation threshold for nuclear PKA holoenzyme, thereby converting spatially distinct second messenger signals to temporally controlled nuclear kinase activity.

Indexed as

Adenylyl CyclasesA Kinase Anchor ProteinsCell NucleusCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4CytoplasmEnzyme InhibitorsHEK293 CellsHoloenzymesHumansModels, BiologicalPhosphoric Diester HydrolasesSignal TransductionSodium BicarbonateSolubilityAdenylyl CyclasesA Kinase Anchor ProteinsCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic Nucleotide Phosphodiesterases, Type 4Enzyme InhibitorsHoloenzymesPhosphoric Diester HydrolasesSodium Bicarbonate

Identifiers

PMID22366721
PMCPMC3307945
OpenAlexW2013955369

What OpenQuestion holds

Textmetadata
LicenceTDM
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.