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


CONCLUSIONS
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.
Won
Hong-Hee
HH
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-710, South Korea. honghee.won@gmail.com
Park
Inho
I
Lee
Eunjung
E
Kim
Jong-Won
JW
Lee
Doheon
D
D003198:Computer Simulation; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism*; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D049490:Systems Biology
D017467:Receptors, Erythropoietin; D053628:Receptors, Thrombopoietin; D050791:STAT Transcription Factors; D053612:Janus Kinases