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Autophosphorylation and the Dynamics of the Activation of Lck

Published version
Peer-reviewed

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Authors

Kreusser, Lisa Maria 

Abstract

Abstract: 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.

Description

Keywords

Original Article, Src kinase, Bifurcation, Phosphorylation, Dynamics, T cells

Journal Title

Bulletin of Mathematical Biology

Conference Name

Journal ISSN

0092-8240
1522-9602

Volume Title

83

Publisher

Springer US
Sponsorship
Horizon 2020 (No. 777826 (NoMADS))