Model predictions for the concentration of STAT3_p phosphorylated by JAK and dephosphorylated by SHP-1.

<p>Investigation of the dependence of STAT3 phosphorylation on the relative activities of JAK and SHP. (A) Cartoon diagram of STAT3 phosphorylation and dephosphorylation by JAK and SHP-1, respectively. (B) A comparative analysis of the proposed and applications of the previously published models for STAT3 phosphorylation. Ratios of JAK and SHP-1 are found to be critical for STAT3 phosphorylation response and the differences between the model predictions. The red line shows the predictions by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110913#pone.0110913-Goldbeter1" target="_blank">[6]</a> whereas the black line offers predictions from the presented model. The STAT3 phosphorylation predictions coincide when STAT3 significantly exceeds SHP-1 concentration. (C) The effects of phosphorylation and dephosphorylation rates are studied on the proposed (black line) and previously reported (red line) models <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110913#pone.0110913-Goldbeter1" target="_blank">[6]</a>. We found that our model predicts the modulation of phosphorylated STAT as opposed to the prediction of STAT3 phosphorylation rate offered by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110913#pone.0110913-Goldbeter1" target="_blank">[6]</a>. (D) The comparison between the proposed and the previously model <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110913#pone.0110913-Goldbeter1" target="_blank">[6]</a> is shown as a function of phosphorylation/dephosphorylation rates for various ratios of JAK and SHP-1. This analysis clearly demonstrates the differences in STAT3 phosphorylation predictions due to the underlying assumptions employed in the models.