Mathematics of the NFAT Signaling Pathway

作者：Rendall Alan D^*

来源：SIAM Journal on Applied Dynamical Systems, 2012, 11(3): 988-1006.

DOI：10.1137/120866488

• immunology
• signaling pathway
• chemical reaction network theory

This paper is a mathematical study of some aspects of the signaling pathway leading to the activation of the transcription factor NFAT (nuclear factor of activated T cells). Activation takes place by dephosphorylation at multiple sites. This has been modeled by Salazar and Hofer using a large system of ordinary differential equations depending on many parameters. With the help of chemical reaction network theory we show that for any choice of the parameters this system has a unique stationary solution for each value of the conserved quantity given by the total amount of NFAT and that all solutions converge to this stationary solution at late times. The dephosphorylation is carried out by calcineurin, which in turn is activated by a rise in calcium concentration. We study the way in which the dynamics of the calcium concentration influences NFAT activation, an issue also considered by Salazar and Hofer with the help of a model arising from work of Somogyi and Stucki. Criteria are obtained for convergence to equilibrium of solutions of the model for the calcium concentration.

• 出版日期2012