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Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling t...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282855/ https://www.ncbi.nlm.nih.gov/pubmed/35686730 http://dx.doi.org/10.7554/eLife.78301 |
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author | Mo, Xiaoyi Pang, Peiyuan Wang, Yulin Jiang, Dexiang Zhang, Mengyu Li, Yang Wang, Peiyu Geng, Qizhi Xie, Chang Du, Hai-Ning Zhong, Bo Li, Dongdong Yao, Jing |
author_facet | Mo, Xiaoyi Pang, Peiyuan Wang, Yulin Jiang, Dexiang Zhang, Mengyu Li, Yang Wang, Peiyu Geng, Qizhi Xie, Chang Du, Hai-Ning Zhong, Bo Li, Dongdong Yao, Jing |
author_sort | Mo, Xiaoyi |
collection | PubMed |
description | Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts. |
format | Online Article Text |
id | pubmed-9282855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92828552022-07-15 Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel Mo, Xiaoyi Pang, Peiyuan Wang, Yulin Jiang, Dexiang Zhang, Mengyu Li, Yang Wang, Peiyu Geng, Qizhi Xie, Chang Du, Hai-Ning Zhong, Bo Li, Dongdong Yao, Jing eLife Biochemistry and Chemical Biology Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel implicated in diverse physiopathological processes. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages and dorsal root ganglia (DRG) neurons. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts. eLife Sciences Publications, Ltd 2022-06-10 /pmc/articles/PMC9282855/ /pubmed/35686730 http://dx.doi.org/10.7554/eLife.78301 Text en © 2022, Mo, Pang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Mo, Xiaoyi Pang, Peiyuan Wang, Yulin Jiang, Dexiang Zhang, Mengyu Li, Yang Wang, Peiyu Geng, Qizhi Xie, Chang Du, Hai-Ning Zhong, Bo Li, Dongdong Yao, Jing Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title | Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title_full | Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title_fullStr | Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title_full_unstemmed | Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title_short | Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel |
title_sort | tyrosine phosphorylation tunes chemical and thermal sensitivity of trpv2 ion channel |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282855/ https://www.ncbi.nlm.nih.gov/pubmed/35686730 http://dx.doi.org/10.7554/eLife.78301 |
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