Study of Eps8 in EGFR-mediated mitogenesis and signal transduction

• Main Authors: Tsai-Chien Cheng, 鄭采倩
• Other Authors: Tzeng-Horng Leu
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/32297104077753206178

碩士 === 國立成功大學 === 藥理學研究所 === 93 === 　Eps8 (EGF receptor pathway substrate NO.8) is a common substrate for both EGF receptor (EGFR) tyrosine kinase and cytoplasmic tyrosine kinase Src. It exists in two isoforms p97EPS8 and p68Eps8 in many cell lines. Early studies have indicated that ectopical overexpression of p97Eps8 in EGFR overexpressing cells not only enhances its mitogenic responsiveness to epidermal growth factor, but also elevates EGF-dependent cellular transformation. 　However, we observed that Eps8 expression is elevated in EGFR-overexpressing C3H10T1/2 fibroblast cells (NeoR). Thus, whether Eps8 really participates in EGFR-mediated mitogenesis and transformation becomes an interesting issue. 　To address this, we generated eps8 siRNA and p97eps8-specific siRNA - overexpressing cells from NeoR cells. Interestingly, the EGF-induced cell growth is abolished in both p97eps8siRNA- and eps8 siRNA-overexpressing cells. Thus, Eps8 is indeed involved in EGF-mediated mitogenesis. In addition, we examined the activity of ERK and PI3K within these EGF-stimulated cells and found that as compared with control cells, both ERK and AKT activation was down-regulated in Eps8 knockdown cells. Unexpectedly, the protein expression and Tyr317 phosphorylation of Shc was up-regulated and led to increased interaction between EGFR and Shc.