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Autophosphorylation and the Dynamics of the Activation of Lck
Lck (lymphocyte-specific protein tyrosine kinase) is an enzyme which plays a number of important roles in the function of immune cells. It belongs to the Src family of kinases which are known to undergo autophosphorylation. It turns out that this leads to a remarkable variety of dynamical behaviour...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088428/ https://www.ncbi.nlm.nih.gov/pubmed/33932170 http://dx.doi.org/10.1007/s11538-021-00900-9 |
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author | Kreusser, Lisa Maria Rendall, Alan D. |
author_facet | Kreusser, Lisa Maria Rendall, Alan D. |
author_sort | Kreusser, Lisa Maria |
collection | PubMed |
description | Lck (lymphocyte-specific protein tyrosine kinase) is an enzyme which plays a number of important roles in the function of immune cells. It belongs to the Src family of kinases which are known to undergo autophosphorylation. It turns out that this leads to a remarkable variety of dynamical behaviour which can occur during their activation. We prove that in the presence of autophosphorylation one phenomenon, bistability, already occurs in a mathematical model for a protein with a single phosphorylation site. We further show that a certain model of Lck exhibits oscillations. Finally, we discuss the relations of these results to models in the literature which involve Lck and describe specific biological processes, such as the early stages of T cell activation and the stimulation of T cell responses resulting from the suppression of PD-1 signalling which is important in immune checkpoint therapy for cancer. |
format | Online Article Text |
id | pubmed-8088428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-80884282021-05-05 Autophosphorylation and the Dynamics of the Activation of Lck Kreusser, Lisa Maria Rendall, Alan D. Bull Math Biol Original Article Lck (lymphocyte-specific protein tyrosine kinase) is an enzyme which plays a number of important roles in the function of immune cells. It belongs to the Src family of kinases which are known to undergo autophosphorylation. It turns out that this leads to a remarkable variety of dynamical behaviour which can occur during their activation. We prove that in the presence of autophosphorylation one phenomenon, bistability, already occurs in a mathematical model for a protein with a single phosphorylation site. We further show that a certain model of Lck exhibits oscillations. Finally, we discuss the relations of these results to models in the literature which involve Lck and describe specific biological processes, such as the early stages of T cell activation and the stimulation of T cell responses resulting from the suppression of PD-1 signalling which is important in immune checkpoint therapy for cancer. Springer US 2021-05-01 2021 /pmc/articles/PMC8088428/ /pubmed/33932170 http://dx.doi.org/10.1007/s11538-021-00900-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Kreusser, Lisa Maria Rendall, Alan D. Autophosphorylation and the Dynamics of the Activation of Lck |
title | Autophosphorylation and the Dynamics of the Activation of Lck |
title_full | Autophosphorylation and the Dynamics of the Activation of Lck |
title_fullStr | Autophosphorylation and the Dynamics of the Activation of Lck |
title_full_unstemmed | Autophosphorylation and the Dynamics of the Activation of Lck |
title_short | Autophosphorylation and the Dynamics of the Activation of Lck |
title_sort | autophosphorylation and the dynamics of the activation of lck |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088428/ https://www.ncbi.nlm.nih.gov/pubmed/33932170 http://dx.doi.org/10.1007/s11538-021-00900-9 |
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