Tyrphostin ErbB2 Inhibitors AG825 and AG879 Have Non-specific Suppressive Effects on gp130/ STAT3 Signaling.
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.
Lee
Hyun Kyoung
HK
Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University, Busan 602-714, Korea.
Seo
In Ae
IA
Lee
Sang Hwa
SH
Seo
Su-Young
SY
Kim
Kyung Sup
KS
Park
Hwan Tae
HT