Evidence map›Paper›PMID 38537638›Full record

ArticleMolecular cell2024

Molecular determinants and signaling effects of PKA RIα phase separation.

Julia C Hardy, Emily H Pool, Jessica G H Bruystens, Xin Zhou, Qingrong Li, Daojia R Zhou, Max Palay, Gerald Tan, Lisa Chen, Jaclyn L C Choi and 6 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
6.5field-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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Julia C HardyDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Emily H PoolDepartment 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.
Jessica G H BruystensDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Xin ZhouDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Qingrong LiSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Daojia R ZhouDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Max PalayDepartment 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.
Gerald TanDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Lisa ChenDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Jaclyn L C ChoiDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Ha Neul LeeDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Stefan StrackDepartment of Pharmacology, University of Iowa, Iowa City, IA 52242, USA.
Dong WangDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, 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; Shu Chien-Gene Lay 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; Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jzhang32@health.ucsd.edu.
University of California San Diego · USUniversity of Iowa · US

Funding

Live-cell Activity Architecture in CancerR35CA197622 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Jin Zhang · 2015 to 2026
$11.2M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
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
Molecular Mechanisms for DNA Damage Processing by Transcription MachineryR01GM102362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, DONG · 2013 to 2025
$5.6M
NCI NIH HHS R35 CA197622NIDDK NIH HHS R01 DK073368NIGMS NIH HHS R01 GM102362NIGMS NIH HHS R35 GM130389NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Spatiotemporal regulation of intracellular signaling molecules, such as the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures proper cellular function. Liquid-liquid phase separation (LLPS) of the ubiquitous PKA regulatory subunit RIα promotes cAMP compartmentation and signaling specificity. However, the molecular determinants of RIα LLPS remain unclear. Here, we reveal that two separate dimerization interfaces, combined with the cAMP-induced unleashing of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence, drive RIα condensate formation in the cytosol of mammalian cells, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RIα pseudosubstrate region is critically involved in forming a non-canonical R:C complex, which recruits active PKA-C to RIα condensates to maintain low basal PKA activity in the cytosol. Our results suggest that RIα LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity.

Indexed as

Cyclic AMP-Dependent Protein Kinase RIalpha SubunitPhase SeparationAnimalsCyclic AMPCyclic AMP-Dependent Protein KinasesMammalsSignal TransductionCyclic AMPCyclic AMP-Dependent Protein Kinase RIalpha SubunitCyclic AMP-Dependent Protein Kinasesbiomolecular condensatesintrinsically disordered regionprotein kinasesignaling compartmentation

Identifiers

PMID38537638
PMCPMC11031308
OpenAlexW4393203842

What Socratic holds

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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 Socratic graph.