Department of Physiology, Medical Science Research Institute, College of Medicine, Dong-A University, Busan 602-714, Korea.
Korean J Physiol Pharmacol. 2008 Oct;12(5):281-6. doi: 10.4196/kjpp.2008.12.5.281. Epub 2008 Oct 31.
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.
虽然 gp130 与 ErbB 家族之间的相互作用在癌细胞中经常被观察到，但这种相互作用的机制仍不清楚且存在争议。在本研究中，我们发现 ErbB2 的特定 tyrphostin 抑制剂（AG825 和 AG879），但不是 ErbB1 抑制剂（AG1478），可以抑制施万细胞瘤细胞中 IL-6 诱导的 STAT3 酪氨酸磷酸化。然而，并未观察到 IL-6 通过转导激活 ErbB2 的生化证据。此外，用特异性 RNAi 或转染缺乏细胞内结构域的 ErbB2 突变体抑制 ErbB2 表达，也不能抑制 IL-6 诱导的 STAT3 酪氨酸磷酸化。因此，tyrphostins（已知是 ErbB2 激酶的特异性抑制剂）可能对 IL-6/STAT3 途径具有非特异性抑制作用。
