Comparative analysis of the JAK/STAT signaling through erythropoietin receptor and thrombopoietin receptor using a systems approach

Abstract

Background: The Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is one of the most important targets for myeloproliferative disorder (MPD). Although several efforts toward modeling the pathway using systems biology have been successful, the pathway was not fully investigated in regard to understanding pathological context and to model receptor kinetics and mutation effects. Results: We have performed modeling and simulation studies of the JAK/STAT pathway, including the kinetics of two associated receptors (the erythropoietin receptor and thrombopoietin receptor) with the wild type and a recently reported mutation (JAK2V617F) of the JAK2 protein. Conclusion: We found that the different kinetics of those two receptors might be important factors that affect the sensitivity of JAK/STAT signaling to the mutation effect. In addition, our simulation results support clinically observed pathological differences between the two subtypes of MPD with respect to the JAK2V617F mutation.