This paper presents a mathematical model for IL-6 (interleukin-6) signal transduction in hepatocytes. Signaling by IL-6 involves two pathways. In the first pathway, Janus-associated kinases (JAK) & signal transducers and transcription factors (STAT 3) are activated while the second pathway involves the activation of mitogen-activated protein kinases (MAPK). However, simultaneous signaling through both JAK/STAT and MAPK pathways has been studied only in few cases (Schaper et. al (1998)) and the interaction between these pathways is not yet clearly understood. In this work, a mathematical model has been developed that integrates signaling through both pathways. The presented model is used to analyze the effect of SHP-2 (domain containing tyrosine phosphatase 2) and SOCS3 (suppressor of cytokine signaling 3), on signal transduction induced by IL-6. The results obtained from the developed model show that SHP-2 and SOCS3 do not act independently of each other. SHP-2 and SOCS3 influence signal transduction through the JAK/STAT as well as the MAPK pathway.
Proceedings Foundations of Systems Biology in Engineering 2005, Santa Barbara, pp. 188-192 (2005)