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A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1
The transport of the K(+) channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760375/ https://www.ncbi.nlm.nih.gov/pubmed/26743085 http://dx.doi.org/10.1242/jcs.180182 |
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author | Kilisch, Markus Lytovchenko, Olga Arakel, Eric C. Bertinetti, Daniela Schwappach, Blanche |
author_facet | Kilisch, Markus Lytovchenko, Olga Arakel, Eric C. Bertinetti, Daniela Schwappach, Blanche |
author_sort | Kilisch, Markus |
collection | PubMed |
description | The transport of the K(+) channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic. |
format | Online Article Text |
id | pubmed-4760375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47603752016-03-01 A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 Kilisch, Markus Lytovchenko, Olga Arakel, Eric C. Bertinetti, Daniela Schwappach, Blanche J Cell Sci Research Article The transport of the K(+) channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic. The Company of Biologists Ltd 2016-02-15 /pmc/articles/PMC4760375/ /pubmed/26743085 http://dx.doi.org/10.1242/jcs.180182 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Kilisch, Markus Lytovchenko, Olga Arakel, Eric C. Bertinetti, Daniela Schwappach, Blanche A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title | A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title_full | A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title_fullStr | A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title_full_unstemmed | A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title_short | A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 |
title_sort | dual phosphorylation switch controls 14-3-3-dependent cell surface expression of task-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760375/ https://www.ncbi.nlm.nih.gov/pubmed/26743085 http://dx.doi.org/10.1242/jcs.180182 |
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