Elucidation of the mechanism by which diacylglycerol kinase η regulates cell proliferation

Ras/B-Raf/C-Raf/MEK/ERK通路(ERK通路)对包括细胞增殖在内的许多细胞过程的调控起着至关重要的作用。在这里，我们发现依赖小干扰RNA的二酰基甘油激酶η(DGKERK)的敲除会损害由表皮生长因子激活的η通路。DGKη的过表达可以激活DGK活性不依赖的ERK通路，提示DGKη是一种适配蛋白。我们发现DGKη能激活C-Raf，但不能激活B-Raf。此外，敲除Dgkη可抑制表皮生长因子诱导的C-Raf和B-Raf的异构化。DGKη与B-Raf和C-Raf相互作用，调节表皮生长因子诱导的B-Raf和C-Raf从胞浆向膜的募集。这些结果支持DGKERK作为ERK信号级联中的一个新的关键调节成分。

The Ras/B-Raf/C-Raf/MEK/ERK pathway (ERK pathway) is critical for the control of many cellular processes including proliferation. Here we showed that siRNA-dependent knockdown of diacylglycerol kinase η (DGK η) impairs the ERK pathway activated by epidermal growth factor (EGF) in HeLa cells. The overexpression of DGK η could activate the ERK pathway in a DGK activity-independent manner, suggesting that DGK η serves as an adaptor protein. We revealed that DGK η activates C-Raf but not B-Raf. Moreover, knockdown of DGK η inhibited EGF-induced heterodimerization of C-Raf with B-Raf. DGK η physically interacted with B-Raf and C-Raf and regulated EGF-induced recruitment of B-Raf and C-Raf from the cytosol to membranes. These results support that DGK η acts as a novel critical regulatory component of the ERK signaling cascade.