ArticleMolecular cell2013
Protons as second messenger regulators of G protein signaling.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 90 citations in OpenAlex.
- Article
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- Importance of proteins and mitochondrial changes as freshness indicators in fish muscle post-mortem.Journal of the science of food and agriculture · 2025Review
- Molecular and functional profiling of Gαi as an intracellular pH sensor.Nature communications · 2025Article
- The role of ribosomal protein networks in ribosome dynamics.Nucleic acids research · 2025Article
- CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy.Molecular biology of the cell · 2025Article
- Shared and redundant proteins coordinate signal cross-talk between MAPK pathways in yeast.Molecular biology of the cell · 2024Article
- Stress pathway outputs are encoded by pH-dependent clustering of kinase components.Nature communications · 2024Article
- A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.Nature communications · 2024Article
- Advances in yeast synthetic biology for human G protein-coupled receptor biology and pharmacology.Current opinion in biotechnology · 2024Review
- Intracellular acidification and glycolysis modulate inflammatory pathway in senescent cells.Journal of biochemistry · 2024Article
- Molecular annotation of G protein variants in a neurological disorder.Cell reports · 2023Article
- Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt CaAmerican journal of respiratory cell and molecular biology · 2023Article
- PacBio Full-Length Transcriptome Sequencing Reveals the Mechanism of Salt Stress Response inPlants (Basel, Switzerland) · 2023Article
- Article
- Catalytic site mutations confer multiple states of G protein activation.Science signaling · 2023Article
- Effects of pH alterations on stress- and aging-induced protein phase separation.Cellular and molecular life sciences : CMLS · 2022Review
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- Proton-gated coincidence detection is a common feature of GPCR signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In response to environmental stress, cells often generate pH signals that serve to protect vital cellular components and reprogram gene expression for survival. A major barrier to our understanding of this process has been the identification of signaling proteins that detect changes in intracellular pH. To identify candidate pH sensors, we developed a computer algorithm that searches proteins for networks of proton-binding sidechains. This analysis indicates that Gα subunits, the principal transducers of G protein-coupled receptor (GPCR) signals, are pH sensors. Our structure-based calculations and biophysical investigations reveal that Gα subunits contain networks of pH-sensing sidechains buried between their Ras and helical domains. Further, we show that proton binding induces changes in conformation that promote Gα phosphorylation and suppress receptor-initiated signaling. Together, our computational, biophysical, and cellular analyses reveal an unexpected function for G proteins as mediators of stress-response signaling.
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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.