Evidence map›Paper›PMID 32846158›Full record

ArticleCell2020

Phase Separation of a PKA Regulatory Subunit Controls cAMP Compartmentation and Oncogenic Signaling.

Jason Z Zhang, Tsan-Wen Lu, Lucas M Stolerman, Brian Tenner, Jessica R Yang, Jin-Fan Zhang, Martin Falcke, Padmini Rangamani, Susan S Taylor, Sohum Mehta and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.

0numbers the graph read from it
0cells of the map it votes in
200citing papers in PubMed
–field-weighted citation impact
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

200 citing papers in PubMed.

  1. Beta-Arrestin-2 Binds to Nucleolar Organizing Regions With P2X7 Receptor Stimulation and During Cell Division.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Article
  3. Article
  4. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Directly adopting inverse biosensors to image live cell enzyme activities in nanodomains.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026
    Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jason Z ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Tsan-Wen LuDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Lucas M StolermanDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Brian TennerDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Jessica R YangDepartment of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jin-Fan ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Martin FalckeMathematical Cell Physiology, Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany; Department of Physics, Humboldt University, 12489 Berlin, Germany.
Padmini RangamaniDepartment of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
Susan S TaylorDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Sohum MehtaDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Jin ZhangDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jzhang32@ucsd.edu.

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jesse Nodora · 1985 to 2026
$124.9M
Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
Mechanisms of Compartmentalized cAMP SignalingR01DK073368 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2006 to 2026
$7.6M
Lessons Learned from PKA: Assembly of Dynamic Macromolecular SwitchesR35GM130389 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUSAN S. TAYLOR · 2019 to 2026
$5.7M
NCI NIH HHS P30 CA023100NCI NIH HHS R35 CA197622NIDDK NIH HHS R01 DK073368NIGMS NIH HHS R35 GM130389
6 · The paper itself

Abstract

The fidelity of intracellular signaling hinges on the organization of dynamic activity architectures. Spatial compartmentation was first proposed over 30 years ago to explain how diverse G protein-coupled receptors achieve specificity despite converging on a ubiquitous messenger, cyclic adenosine monophosphate (cAMP). However, the mechanisms responsible for spatially constraining this diffusible messenger remain elusive. Here, we reveal that the type I regulatory subunit of cAMP-dependent protein kinase (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) as a function of cAMP signaling to form biomolecular condensates enriched in cAMP and PKA activity, critical for effective cAMP compartmentation. We further show that a PKA fusion oncoprotein associated with an atypical liver cancer potently blocks RIα LLPS and induces aberrant cAMP signaling. Loss of RIα LLPS in normal cells increases cell proliferation and induces cell transformation. Our work reveals LLPS as a principal organizer of signaling compartments and highlights the pathological consequences of dysregulating this activity architecture.

Indexed as

Signal TransductionAnimalsCarcinogenesisCarcinoma, HepatocellularCell CompartmentationCell Line, TumorCell ProliferationCyclic AMPCyclic AMP-Dependent Protein Kinase RIalpha SubunitCyclic AMP-Dependent Protein KinasesCytoplasmHSP40 Heat-Shock ProteinsHumansLiver NeoplasmsMiceOncogenesCyclic AMPCyclic AMP-Dependent Protein Kinase RIalpha SubunitCyclic AMP-Dependent Protein KinasesDNAJB1 protein, humanHSP40 Heat-Shock ProteinsRecombinant Fusion ProteinsbiosensorDnaJB1-PKAfibrolamellar carcinomaFLCFRETlive cell imagingmembraneless organellesignal transductionsplit GFP

Identifiers

PMID32846158
PMCPMC7502557

What OpenQuestion holds

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Registered trials

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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.