Evidence map›Paper›PMID 31844302›Full record

ArticleNature chemical biology2020

Artificial signaling in mammalian cells enabled by prokaryotic two-component system.

Alain Mazé, Yaakov Benenson

Abstract read
In one paragraph

Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024
    Review
  6. Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024
    Article
  7. Article
  8. Review
  9. Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023
    Article
  10. Article
  11. Engineering transmembrane signal transduction in synthetic membranes using two-component systems.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Frontiers in immunology · 2023
    Article
  13. Review
  14. Article
  15. Engineering living therapeutics with synthetic biology.Nature reviews. Drug discovery · 2021
    Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Alain MazéDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.ORCID http://orcid.org/0000-0003-0873-3690
Yaakov BenensonDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. kobi.benenson@bsse.ethz.ch.ORCID http://orcid.org/0000-0003-1880-6507

Funding

Swiss National Science Foundation 149802
6 · The paper itself

Abstract

Augmenting live cells with new signal transduction capabilities is a key objective in genetic engineering and synthetic biology. We showed earlier that two-component signaling pathways could function in mammalian cells, albeit while losing their ligand sensitivity. Here, we show how to transduce small-molecule ligands in a dose-dependent fashion into gene expression in mammalian cells using two-component signaling machinery. First, we engineer mutually complementing truncated mutants of a histidine kinase unable to dimerize and phosphorylate the response regulator. Next, we fuse these mutants to protein domains capable of ligand-induced dimerization, which restores the phosphoryl transfer in a ligand-dependent manner. Cytoplasmic ligands are transduced by facilitating mutant dimerization in the cytoplasm, while extracellular ligands trigger dimerization at the inner side of a plasma membrane. These findings point to the potential of two-component regulatory systems as enabling tools for orthogonal signaling pathways in mammalian cells.

Indexed as

Bacterial Outer Membrane Proteinsbeta-ArrestinsDNA-Binding ProteinsEscherichia coli ProteinsGene Expression RegulationHEK293 CellsHistidine KinaseHumansMultienzyme ComplexesMutationPhosphorylationProtein DomainsProtein KinasesProtein MultimerizationReceptors, G-Protein-CoupledRecombinant Fusion ProteinsBacterial Outer Membrane Proteinsbeta-ArrestinsDNA-Binding ProteinsenvZ protein, E coliEscherichia coli ProteinsHistidine KinaseMultienzyme ComplexesNarL protein, E colinarX protein, E coliProtein KinasesReceptors, G-Protein-CoupledRecombinant Fusion ProteinsTacrolimus Binding Protein 1A

Identifiers

PMID31844302
PMCPMC6982536

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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.