通过Gab1 plekstrin同源（PH）结构域诱饵同时抑制Erk和Akt/PKB激活。
Simultaneous suppression of Erk and Akt/PKB activation by a Gab1 pleckstrin homology (PH) domain decoy.
作者信息
Ren Yuan, Wu Jie
机构信息
Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
出版信息
Anticancer Res. 2003 Jul-Aug;23(4):3231-6.
BACKGROUND
Gab1 is a pleckstrin homology (PH) domain containing docking protein that mediates EGF-induced Erk and Akt/PKB activation. Using a decoy strategy, we explored the Gab1 PH domain as a potential target for simultaneous inhibition of Erk and Akt/PKB activation.
MATERIALS AND METHODS
MDA-MB-468 and SK-BR-3 derived cell lines were established for doxycycline-inducible expression of a Gab1 PH domain decoy. Erk and Akt activation, matrix metalloprotease-9 (MMP-9) secretion and cell motility were analyzed.
RESULTS
Expression of the Gab1 PH domain decoy in these cells suppressed EGF-induced Erk2 and Akt/PKB activation, MMP-9 secretion and cell migration. The constitutively active Akt/PKB in the PTEN-negative MDA-MB-468 cells was also suppressed by the Gab1 PH domain decoy.
CONCLUSION
These results illustrate that the Gab1 PH domain is a potential target for antagonizing ErbB activation and PTEN inactivation, and for suppression of ErbB-induced metastatic activities in breast cancer cells.
背景
Gab1是一种含有pleckstrin同源（PH）结构域的对接蛋白，介导表皮生长因子（EGF）诱导的细胞外信号调节激酶（Erk）和蛋白激酶B（Akt/PKB）的激活。我们采用诱饵策略，探索Gab1的PH结构域作为同时抑制Erk和Akt/PKB激活的潜在靶点。
材料与方法
建立了源自MDA-MB-468和SK-BR-3细胞系，用于强力霉素诱导表达Gab1 PH结构域诱饵。分析了Erk和Akt的激活、基质金属蛋白酶-9（MMP-9）的分泌及细胞运动性。
结果
Gab1 PH结构域诱饵在这些细胞中的表达抑制了EGF诱导的Erk2和Akt/PKB激活、MMP-9分泌及细胞迁移。PTEN阴性的MDA-MB-468细胞中组成型激活的Akt/PKB也被Gab1 PH结构域诱饵所抑制。
结论
这些结果表明，Gab1的PH结构域是拮抗表皮生长因子受体（ErbB）激活和PTEN失活、抑制ErbB诱导的乳腺癌细胞转移活性的潜在靶点。
Zotero 插件