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The receptor PTPRU is a redox sensitive pseudophosphatase
The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proxim...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320164/ https://www.ncbi.nlm.nih.gov/pubmed/32591542 http://dx.doi.org/10.1038/s41467-020-17076-w |
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author | Hay, Iain M. Fearnley, Gareth W. Rios, Pablo Köhn, Maja Sharpe, Hayley J. Deane, Janet E. |
author_facet | Hay, Iain M. Fearnley, Gareth W. Rios, Pablo Köhn, Maja Sharpe, Hayley J. Deane, Janet E. |
author_sort | Hay, Iain M. |
collection | PubMed |
description | The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proximal (D1) domain and an inactive distal (D2) pseudophosphatase domain. Here we demonstrate that PTPRU is unique amongst the RPTPs in possessing two pseudophosphatase domains. The PTPRU-D1 displays no detectable catalytic activity against a range of phosphorylated substrates and we show that this is due to multiple structural rearrangements that destabilise the active site pocket and block the catalytic cysteine. Upon oxidation, this cysteine forms an intramolecular disulphide bond with a vicinal “backdoor” cysteine, a process thought to reversibly inactivate related phosphatases. Importantly, despite the absence of catalytic activity, PTPRU binds substrates of related phosphatases strongly suggesting that this pseudophosphatase functions in tyrosine phosphorylation by competing with active phosphatases for the binding of substrates. |
format | Online Article Text |
id | pubmed-7320164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73201642020-06-30 The receptor PTPRU is a redox sensitive pseudophosphatase Hay, Iain M. Fearnley, Gareth W. Rios, Pablo Köhn, Maja Sharpe, Hayley J. Deane, Janet E. Nat Commun Article The receptor-linked protein tyrosine phosphatases (RPTPs) are key regulators of cell-cell communication through the control of cellular phosphotyrosine levels. Most human RPTPs possess an extracellular receptor domain and tandem intracellular phosphatase domains: comprising an active membrane proximal (D1) domain and an inactive distal (D2) pseudophosphatase domain. Here we demonstrate that PTPRU is unique amongst the RPTPs in possessing two pseudophosphatase domains. The PTPRU-D1 displays no detectable catalytic activity against a range of phosphorylated substrates and we show that this is due to multiple structural rearrangements that destabilise the active site pocket and block the catalytic cysteine. Upon oxidation, this cysteine forms an intramolecular disulphide bond with a vicinal “backdoor” cysteine, a process thought to reversibly inactivate related phosphatases. Importantly, despite the absence of catalytic activity, PTPRU binds substrates of related phosphatases strongly suggesting that this pseudophosphatase functions in tyrosine phosphorylation by competing with active phosphatases for the binding of substrates. Nature Publishing Group UK 2020-06-26 /pmc/articles/PMC7320164/ /pubmed/32591542 http://dx.doi.org/10.1038/s41467-020-17076-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hay, Iain M. Fearnley, Gareth W. Rios, Pablo Köhn, Maja Sharpe, Hayley J. Deane, Janet E. The receptor PTPRU is a redox sensitive pseudophosphatase |
title | The receptor PTPRU is a redox sensitive pseudophosphatase |
title_full | The receptor PTPRU is a redox sensitive pseudophosphatase |
title_fullStr | The receptor PTPRU is a redox sensitive pseudophosphatase |
title_full_unstemmed | The receptor PTPRU is a redox sensitive pseudophosphatase |
title_short | The receptor PTPRU is a redox sensitive pseudophosphatase |
title_sort | receptor ptpru is a redox sensitive pseudophosphatase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320164/ https://www.ncbi.nlm.nih.gov/pubmed/32591542 http://dx.doi.org/10.1038/s41467-020-17076-w |
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