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

Ras/B-Raf/C-Raf/MEK/ERK通路（ERK通路）对于控制包括增殖在内的许多细胞过程至关重要。在此，我们发现，siRNA依赖性敲低二酰基甘油激酶η（DGK η）会损害HeLa细胞中表皮生长因子（EGF）激活的ERK通路。DGK η的过表达可以以不依赖于DGK活性的方式激活ERK通路，表明DGK η作为接头蛋白。我们发现DGK η激活C-Raf而不激活B-Raf。此外，DGK η的敲低抑制EGF诱导的C-Raf与B-Raf的异二聚化。DGK η与B-Raf和C-Raf物理相互作用，并调节EGF诱导的B-Raf和C-Raf从胞质溶胶到膜的募集。这些结果支持DGK η作为ERK信号级联的新的关键调节组分。

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.