ArticleNature communications2020
Phosphoregulated orthogonal signal transduction in mammalian cells.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Engineering signalling pathways in mammalian cells.Nature biomedical engineering · 2024Review
- Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024Article
- Programmable synthetic receptors: the next-generation of cell and gene therapies.Signal transduction and targeted therapy · 2024Review
- Mechanistic and biophysical characterization of polymyxin resistance response regulator PmrA inFrontiers in microbiology · 2024Article
- Customizing cellular signal processing by synthetic multi-level regulatory circuits.Nature communications · 2023Review
- Engineering synthetic phosphorylation signaling networks in human cells.bioRxiv : the preprint server for biology · 2023Article
- Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023Review
- Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction.Nature communications · 2023Article
- Small molecule-inducible gene regulatory systems in mammalian cells: progress and design principles.Current opinion in biotechnology · 2022Review
- Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles.Nature communications · 2022Article
- The evolution of synthetic receptor systems.Nature chemical biology · 2022Review
- Article
- Context-aware synthetic biology by controller design: Engineering the mammalian cell.Cell systems · 2021Review
- Nitrate- and Nitrite-Sensing Histidine Kinases: Function, Structure, and Natural Diversity.International journal of molecular sciences · 2021Review
- Dual Systems for Enhancing Control of Protein Activity through Induced Dimerization Approaches.Advanced biology · 2021Review
- O-GlcNAc Engineering on a Target Protein in Cells with Nanobody-OGT and Nanobody-splitOGA.Current protocols · 2021Article
- Programmable protein circuit design.Cell · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Orthogonal tools for controlling protein function by post-translational modifications open up new possibilities for protein circuit engineering in synthetic biology. Phosphoregulation is a key mechanism of signal processing in all kingdoms of life, but tools to control the involved processes are very limited. Here, we repurpose components of bacterial two-component systems (TCSs) for chemically induced phosphotransfer in mammalian cells. TCSs are the most abundant multi-component signal-processing units in bacteria, but are not found in the animal kingdom. The presented phosphoregulated orthogonal signal transduction (POST) system uses induced nanobody dimerization to regulate the trans-autophosphorylation activity of engineered histidine kinases. Engineered response regulators use the phosphohistidine residue as a substrate to autophosphorylate an aspartate residue, inducing their own homodimerization. We verify this approach by demonstrating control of gene expression with engineered, dimerization-dependent transcription factors and propose a phosphoregulated relay system of protein dimerization as a basic building block for next-generation protein circuits.
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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.