Model-driven experimental analysis of the function of SHP-2 in IL-6-induced Jak/STAT signaling

摘要: Misregulated interleukin-6 (IL-6)-induced Jak/STAT signaling contributes to many diseases. Under non-pathological conditions is tightly regulated by a complex network of regulators. One these regulators the protein tyrosine phosphatase SH2-containing 2 (SHP2). Although SHP2 known be negative regulator IL-6-induced signaling, its exact molecular function not entirely understood. To elucidate in IL-6 we followed systems biology approach, which modeling, stepwise model refinement, and experimental analysis are closely linked. We come up with an identifiable early that describes data proves predictive. The model-based implies (1) association gp80 gp130 (2) STAT3 dimerization at receptor essential for dynamics pathway activation, (3) phosphorylation nonlinear. Furthermore, modeling results indicate does act as feedback inhibitor phase signaling. However, reveal exhibits basal repressory function.