GGC represses activation of kinases controlling STAT3
phosphorylation.
As STAT3 can be activated by upstream kinases, we deciphered the actions
of GGC on the phosphorylation of JAK1, JAK2, and Src. GGC inhibited
p-JAK1, p-JAK2, and p-Src levels (Fig. 1F) without altering total JAK1,
JAK2, and Src proteins. We also found that IL-6 promoted phosphorylation
of STAT3 was maximally induced at 15 min after IL-6 treatment (Fig. 2A).
As shown Fig. 2B and 2C, GGC attenuated IL-6-driven STAT3
phosphorylation and upstream signaling proteins in time dependent
manner. In addition, H1299 cells were transfected with STAT3-luciferase
construct and when the cells exposed to GGC prior to stimulation,
IL-6-induced STAT3 activity was repressed significantly.