Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Taiping Road, Haidian, Beijing, 100850, People's Republic of China.
Mol Cell Biochem. 2014 Apr;389(1-2):239-47. doi: 10.1007/s11010-013-1945-7. Epub 2014 Jan 8.
Previously, we demonstrated that SGEF enhances EGFR stability; however, SGEF-mediated downstream signaling of EGFR is not well understood. Here, we show that SGEF enhances EGF-induced ERK1/2 activation independent of its guanine nucleotide exchange (GEF) activity. We further show that SGEF interacts with Grb2, a critical downstream transducer of EGFR. Surprisingly, we found that interaction of Grb2 to SGEF antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation. Taken together, this study reports a novel function of SGEF that excludes GEF and also provides important insights into the complex role of Grb2 in EGFR signal transduction.
此前，我们证明了 SGEF 可增强 EGFR 的稳定性；然而，SGEF 介导的 EGFR 下游信号通路尚不清楚。在这里，我们表明 SGEF 增强了 EGF 诱导的 ERK1/2 激活，而不依赖其鸟嘌呤核苷酸交换（GEF）活性。我们还表明，SGEF 与 Grb2 相互作用，Grb2 是 EGFR 的关键下游转导物。令人惊讶的是，我们发现 Grb2 与 SGEF 的相互作用拮抗了 SGEF 增强 EGF 诱导的 ERK1/2 激活的能力。总之，本研究报道了 SGEF 的一个新功能，该功能排除了 GEF，还为 Grb2 在 EGFR 信号转导中的复杂作用提供了重要的见解。
