Although the interaction between gp130 and the ErbB family has frequently been shown in
cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific
tyrphostin inhibitors of ErbB2 (
AG825 and
AG879), but not ErbB1 inhibitor (
AG1478), suppressed IL-6-induced
tyrosine phosphorylation of STAT3 in
schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by
IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced
tyrosine phosphorylation of STAT3. Thus, it seems that
tyrphostins, which are known as specific inhibitors of the ErbB2
kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.