Evidence map›Paper›PMID 27542194›Full record

ArticleeLife2016

Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1.

Shekhar Srivastava, Saswati Panda, Zhai Li, Stephen R Fuhs, Tony Hunter, Dennis J Thiele, Stevan R Hubbard, Edward Y Skolnik

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Histidine Phosphorylation: Protein Kinases and Phosphatases.International journal of molecular sciences · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Meeting a threat of the Anthropocene: Taste avoidance of metal ions byProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. 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 · 2021
    Article
  19. Article
  20. Immune Checkpoint Inhibitors Regulate KFrontiers in pharmacology · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Shekhar SrivastavaDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
Saswati PandaDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
Zhai LiDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.
Stephen R FuhsMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
Tony HunterMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.ORCID 0000-0002-7691-6993
Dennis J ThieleDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, United States.
Stevan R HubbardDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.ORCID 0000-0002-2707-9383
Edward Y SkolnikDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States.

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Salk Institute Cancer Training GrantT32CA009370 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Diana Clare Hargreaves, Jan Karlseder · 1986 to 2026
$8.6M
Copper Homeostasis in MammalsR01DK074192 · NIDDK · DUKE UNIVERSITY · PI MATSUNAMI, HIROAKI · 2006 to 2021
$5.2M
The Invisible Phosphoproteome: New Tools to Study Histidine PhosphorylationR01CA194584 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HUNTER, TONY R. · 2015 to 2019
$2.2M
Regulation of the potassium channel IK1 by calcium and histidine phosphorylationR21AI107443 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HUBBARD, STEVAN R. · 2016 to 2017
$466k
NCI NIH HHS P30 CA014195NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA194584NIAID NIH HHS R21 AI107443NIDDK NIH HHS R01 DK074192
6 · The paper itself

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.

Indexed as

AnimalsCD4-Positive T-LymphocytesCells, CulturedCopperCytokinesEnzyme InhibitorsHistidineHumansIntermediate-Conductance Calcium-Activated Potassium ChannelsMiceNucleoside-Diphosphate KinasePatch-Clamp TechniquesPhosphorylationCopperCytokinesEnzyme InhibitorsHistidineIntermediate-Conductance Calcium-Activated Potassium ChannelsKCNN4 protein, humanNDPK-B protein, humanNucleoside-Diphosphate Kinasecell biologycopper inhibitionhistidine phosphorylationnonepotassium channel

Identifiers

PMID27542194
PMCPMC5005030

What OpenQuestion holds

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Registered trials

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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.