ArticleeLife2016
Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Using phage display for rational engineering of a higher-affinity humanized 3' phosphohistidine-specific antibody.Communications chemistry · 2025Article
- Decoding protein N-phosphorylation functionality and sequence patterns.Briefings in bioinformatics · 2025Article
- Are you having a LaPh? Diverse roles of Labile Phosphorylation in mammalian cells.Biochemical Society transactions · 2025Review
- Comprehensive Phenotypic and Proteomic Analyses of Human Reticulocyte Maturation.Blood red cells & iron · 2025Article
- Cryo-EM Detection of AMPylated Histidine Implies Covalent Catalysis in AMPylation Mediated by a Bacterial Effector.Journal of molecular biology · 2025Article
- Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling.Nature chemistry · 2024Article
- Kinase-catalyzed biotinylation for discovery and validation of substrates to multispecificity kinases NME1 and NME2.The Journal of biological chemistry · 2024Article
- Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024Review
- Intracellular acidity impedes KCa3.1 activation by Riluzole and SKA-31.Frontiers in pharmacology · 2024Article
- Derivatives of the Fungal Natural Product Illudalic Acid Inhibit the Activity of Protein Histidine Phosphatase PHPT1.ChemMedChem · 2023Article
- Histidine dephosphorylation of the Gβ protein GPB-1 promotes axon regeneration in C. elegans.EMBO reports · 2022Article
- Synthesis of a Novel Unexpected Cu(II)-Thiazolidine Complex-X-ray Structure, Hirshfeld Surface Analysis, and Biological Studies.Molecules (Basel, Switzerland) · 2022Article
- Meeting a threat of the Anthropocene: Taste avoidance of metal ions byProceedings of the National Academy of Sciences of the United States of America · 2022Article
- A journey from phosphotyrosine to phosphohistidine and beyond.Molecular cell · 2022Review
- Channelopathy-causing mutations in the SCell calcium · 2022Article
- Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis.Frontiers in immunology · 2022Review
- The many ways that nature has exploited the unusual structural and chemical properties of phosphohistidine for use in proteins.The Biochemical journal · 2021Review
- Structural basis for differential recognition of phosphohistidine-containing peptides by 1-pHis and 3-pHis monoclonal antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- LY294002 Inhibits Intermediate Conductance Calcium-Activated Potassium (KCa3.1) Current in Human Glioblastoma Cells.Frontiers in physiology · 2021Article
- Immune Checkpoint Inhibitors Regulate KFrontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
KCa2.1, KCa2.2, KCa2.3 and KCa3.1 constitute a family of mammalian small- to intermediate-conductance potassium channels that are activated by calcium-calmodulin. KCa3.1 is unique among these four channels in that activation requires, in addition to calcium, phosphorylation of a single histidine residue (His358) in the cytoplasmic region, by nucleoside diphosphate kinase-B (NDPK-B). The mechanism by which KCa3.1 is activated by histidine phosphorylation is unknown. Histidine phosphorylation is well characterized in prokaryotes but poorly understood in eukaryotes. Here, we demonstrate that phosphorylation of His358 activates KCa3.1 by antagonizing copper-mediated inhibition of the channel. Furthermore, we show that activated CD4(+) T cells deficient in intracellular copper exhibit increased KCa3.1 histidine phosphorylation and channel activity, leading to increased calcium flux and cytokine production. These findings reveal a novel regulatory mechanism for a mammalian potassium channel and for T-cell activation, and highlight a unique feature of histidine versus serine/threonine and tyrosine as a regulatory phosphorylation site.
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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.