ArticleProceedings of the National Academy of Sciences of the United States of America2014
Transplantation of prokaryotic two-component signaling pathways into mammalian cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
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.
Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Universal strategy to generate lentiviral vectors encoding lethal proteins.Molecular therapy. Advances · 2026Article
- Article
- Conversion of natural cytokine receptors into orthogonal synthetic biosensors.Nature chemical biology · 2025Article
- Small molecule- and cell contact-inducible systems for controlling expression and differentiation in mouse embryonic stem cells.Development (Cambridge, England) · 2025Article
- Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors.ACS synthetic biology · 2025Article
- Dynamic activation of rAAV transgene expression by a small molecule that recruits endogenous transcriptional machinery.Nucleic acids research · 2025Article
- Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024Review
- Enhancing extracellular vesicle cargo loading and functional delivery by engineering protein-lipid interactions.Nature communications · 2024Article
- Engineering CREB-activated promoters for adenosine-induced gene expression.Biotechnology journal · 2024Article
- Engineering transmembrane signal transduction in synthetic membranes using two-component systems.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Natural Killer Cells and Their Implications in Immune Response Diversification in Clinical Pathology and Neoplastic Processes.International journal of molecular sciences · 2023Article
- Virtual cells in a virtual microenvironment recapitulate early development-like patterns in human pluripotent stem cell colonies.Stem cell reports · 2023Article
- The Contribution of the Minimal Promoter Element to the Activity of Synthetic Promoters Mediating CAR Expression in the Tumor Microenvironment.International journal of molecular sciences · 2022Article
- Design of typical genes for heterologous gene expression.Scientific reports · 2022Article
- Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles.Nature communications · 2022Article
- Bacterial two-component systems as sensors for synthetic biology applications.Current opinion in systems biology · 2021Article
- Enhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control.Nature biomedical engineering · 2021Article
- Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity.International journal of molecular sciences · 2021Review
- Programmable protein circuit design.Cell · 2021Review
- Phosphoregulated orthogonal signal transduction in mammalian cells.Nature communications · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.