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

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 res...

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Autores principales: Srivastava, Shekhar, Panda, Saswati, Li, Zhai, Fuhs, Stephen R, Hunter, Tony, Thiele, Dennis J, Hubbard, Stevan R, Skolnik, Edward Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005030/
https://www.ncbi.nlm.nih.gov/pubmed/27542194
http://dx.doi.org/10.7554/eLife.16093
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author Srivastava, Shekhar
Panda, Saswati
Li, Zhai
Fuhs, Stephen R
Hunter, Tony
Thiele, Dennis J
Hubbard, Stevan R
Skolnik, Edward Y
author_facet Srivastava, Shekhar
Panda, Saswati
Li, Zhai
Fuhs, Stephen R
Hunter, Tony
Thiele, Dennis J
Hubbard, Stevan R
Skolnik, Edward Y
author_sort Srivastava, Shekhar
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.16093.001
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spelling pubmed-50050302016-09-07 Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1 Srivastava, Shekhar Panda, Saswati Li, Zhai Fuhs, Stephen R Hunter, Tony Thiele, Dennis J Hubbard, Stevan R Skolnik, Edward Y eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.16093.001 eLife Sciences Publications, Ltd 2016-08-19 /pmc/articles/PMC5005030/ /pubmed/27542194 http://dx.doi.org/10.7554/eLife.16093 Text en © 2016, Srivastava et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Srivastava, Shekhar
Panda, Saswati
Li, Zhai
Fuhs, Stephen R
Hunter, Tony
Thiele, Dennis J
Hubbard, Stevan R
Skolnik, Edward Y
Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title_full Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title_fullStr Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title_full_unstemmed Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title_short Histidine phosphorylation relieves copper inhibition in the mammalian potassium channel KCa3.1
title_sort histidine phosphorylation relieves copper inhibition in the mammalian potassium channel kca3.1
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005030/
https://www.ncbi.nlm.nih.gov/pubmed/27542194
http://dx.doi.org/10.7554/eLife.16093
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