Shemyakin⁻Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Int J Mol Sci. 2019 Mar 26;20(6):1515. doi: 10.3390/ijms20061515.
ErbB2 is an oncogene receptor tyrosine kinase linked to breast cancer. It is a member of the epidermal growth factor receptor (EGFR) minifamily. ErbB2 is currently viewed as an orphan receptor since, by itself, it does not bind EGF-like ligands and can be activated only when overexpressed in malignant cells or complexed with ErbB3, another member of the EGFR minifamily. Here, we report that ErbB2 can be activated by extracellular application of mildly alkaline (pH 8⁻9) media to ErbB2-transfected cells. We also show that the activation of the ErbB2 receptor by alkali is dose-dependent and buffer-independent. The endogenous ErbB2 receptor of A431 cell line can also undergo alkali-dependent autophosphorylation. Thus, we describe a novel ligand-independent mechanism of ErbB2 receptor activation.
erbB2 是一种癌基因受体酪氨酸激酶，与乳腺癌有关。它是表皮生长因子受体 (EGFR) 小家族的成员。erbB2 目前被视为孤儿受体，因为它本身不能结合 EGF 样配体，只能在恶性细胞过度表达或与 EGFR 小家族的另一个成员 erbB3 复合时被激活。在这里，我们报告 erbB2 可以通过向 erbB2 转染细胞施加轻度碱性（pH8-9）介质来激活。我们还表明，碱对 erbB2 受体的激活是剂量依赖性的，并且与缓冲液无关。A431 细胞系的内源性 erbB2 受体也可以经历依赖于碱的自身磷酸化。因此，我们描述了 erbB2 受体激活的一种新的配体非依赖性机制。
