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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...

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Detalles Bibliográficos
Autores principales: Kreusser, Lisa Maria, Rendall, Alan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
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.
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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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