Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range
19.07.2011
Bachmann J, Raue A, Schilling M, Boehm ME, Kreutz C, Kaschek D, Busch H, Gretz N, Lehmann WD, Timmer J, Klingmüller U
Mol Syst Biol 7:516
We establish a dynamic pathway model to dissect the roles of two transcriptional negative feedback regulators in JAK2/STAT5 signaling. By the model, we provide a quantitative link between cell survival and the response of STAT5 in the nucleus. The model shows that the two feedbacks are effective at different ligand concentration ranges. This divided function of dual feedback regulation enables control of STAT5 responses for Epo concentrations that can vary 1000-fold in vivo.
