ArticleMolecular cell2012
Intrinsic negative feedback governs activation surge in two-component regulatory systems.
Article in Molecular cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 52 citations in OpenAlex.
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- PagN: a multifunctional outer membrane protein in Salmonella virulence and host interaction.Archives of microbiology · 2026Review
- Multiple input-multiple output (MIMO) designs in two-component signalling systems of Mycobacterium tuberculosis.FEMS microbiology reviews · 2026Review
- Colistin Resistance in Bacteria: Current Updates on Mechanism of Action and Combating Strategies.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Mutations in two-component signaling systems drive experimental evolution of tigecycline and colistin resistance inAntimicrobial agents and chemotherapy · 2025Article
- Atomic insights into the signaling landscape of E. coli PhoQ histidine kinase from molecular dynamics simulations.Scientific reports · 2024Article
- A Review on Colistin Resistance: An Antibiotic of Last Resort.Microorganisms · 2024Review
- Sequestration of histidine kinases by non-cognate response regulators establishes a threshold level of stimulation for bacterial two-component signaling.Nature communications · 2023Article
- NH125 Sensitizes Staphylococcus aureus to Cell Wall-Targeting Antibiotics through the Inhibition of the VraS Sensor Histidine Kinase.Microbiology spectrum · 2023Article
- Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sites.PLoS computational biology · 2022Article
- Regulation of the Sae Two-Component System by Branched-Chain Fatty Acids in Staphylococcus aureus.mBio · 2022Article
- Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles.Nature communications · 2022Article
- Microbial Adaptation to Enhance Stress Tolerance.Frontiers in microbiology · 2022Review
- How the PhoP/PhoQ System Controls Virulence and MgMicrobiology and molecular biology reviews : MMBR · 2021Review
- Overlaid positive and negative feedback loops shape dynamical properties of PhoPQ two-component system.PLoS computational biology · 2021Article
- MgrB Inactivation Confers Trimethoprim Resistance inFrontiers in microbiology · 2021Article
- Structural asymmetry does not indicate hemiphosphorylation in the bacterial histidine kinase CpxA.The Journal of biological chemistry · 2020Article
- A Membrane-Bound Transcription Factor is Proteolytically Regulated by the AAA+ Protease FtsH in Staphylococcus aureus.Journal of bacteriology · 2020Article
- Acquired Nisin Resistance inmSphere · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
PhoP and PhoQ comprise a two-component system in the bacterium Salmonella enterica. PhoQ is the sensor kinase/phosphatase that modifies the phosphorylation state of the regulator PhoP in response to stimuli. The amount of phosphorylated PhoP surges after activation, then declines to reach a steady-state level. We now recapitulate this surge in vitro by incubating PhoP and PhoQ with ATP and ADP. Mathematical modeling identified PhoQ's affinity for ADP as the key parameter dictating phosphorylated PhoP levels, as ADP promotes PhoQ's phosphatase activity toward phosphorylated PhoP. The lid covering the nucleotide-binding pocket of PhoQ governs the kinase to phosphatase switch because a lid mutation that decreased ADP binding compromised PhoQ's phosphatase activity in vitro and resulted in sustained expression of PhoP-dependent mRNAs in vivo. This feedback mechanism may curtail futile ATP consumption because ADP not only stimulates PhoQ's phosphatase activity but also inhibits ATP binding necessary for the kinase reaction.
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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.