Epidermal Growth Factor Receptor Potentiates MCM7-Mediated DNA Replication through Tyrosine Phosphorylation of Lyn Kinase in Human Cancers

详细信息    查看全文

• 作者：Tzu-Hsuan Huang¹ ; ⁷ ; ⁸ ; Longfei Huo¹ ; ⁷ ; Ying-Nai Wang¹ ; ⁵ ; ⁶ ; Weiya Xia¹ ; Yongkun Wei¹ ; Shih-Shin Chang¹ ; ³ ; Wei-Chao Chang⁴ ; ⁵ ; Yueh-Fu Fang¹ ; Chun-Te Chen¹ ; Jing-Yu Lang¹ ; Chun Tu¹ ; Yan Wang¹ ; Ming-Chuan Hsu¹ ; Hsu-Ping Kuo¹ ; How-Wen Ko¹ ; Jia Shen¹ ; ³ ; Heng-Huan Lee¹ ; ³ ; Pei-Chih Lee¹ ; Yun Wu² ; Chung-Hsuan Chen⁴ ; Mien-Chie Hung¹ ; ³ ; ⁵ ; ⁶ ; ^{mhung@mdanderson.org}
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：10 June, 2013
• 年：2013
• 卷：23
• 期：6
• 页码：796-810
• 全文大小：2287 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

Epidermal growth factor receptor (EGFR) initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56^Lyn, at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other minichromosome maintenance complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56^Lyn Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells.