Autophosphorylation and the Dynamics of the Activation of Lck

Lisa Maria Kreusser, Alan D. Rendall

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number64
JournalBulletin of Mathematical Biology
Volume83
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Bifurcation
  • Dynamics
  • Phosphorylation
  • Src kinase
  • T cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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