Figure 2

Simulated time courses of species in the crosstalk model with continuous exposure to IFN-gamma (0.1 nM) or IL-6 (0.1 nM) after knocking out SHP2 and/or SOCSs. (A) Without SHP-2, IFN-gamma stimulation induced higher levels of STAT1* and STAT3* (about 150%) than normal conditions. (B) Without SHP-2, IL-6 stimulation induced rapid increases in STAT1* and STAT3*. (C) Without SOCS1, IFN-gamma stimulation induced higher levels of STAT1* and STAT3* (about 250%) than normal conditions. (D) Without SOCS3, IL-6 stimulation induced rapid increases in STAT1* and STAT3*, the maximum concentrations of which reached 900 nM and 500 nM, respectively. (E) With SHP-2 and SOCS1 combined knockout, IFN-gamma stimulation produced a similar strength of STAT1* and STAT3*, which both rapidly reached their maximum concentrations of 960 nM and 900 nM, respectively. (F) With SHP-2 and SOCS3 combined knockout, IL-6 produced similar strengths of STAT1* and STAT3*, which both rapidly reached their maximum concentrations of 950 nM and 980 nM, respectively. (G) With SHP-2 and SOCS1 combined knockout, the level of (IFN-R-JAK)2* increased significantly after IFN-gamma stimulation. (H) With SHP-2 and SOCS3 combined knockout, the level of (IL6-gp80-gp130-JAK)2* increased significantly after IL-6 stimulation.