Dept. of Lead Discovery, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str.65, D-88397 Biberach, Germany.
Exp Cell Res. 2011 Jan 1;317(1):42-50. doi: 10.1016/j.yexcr.2010.09.009. Epub 2010 Sep 18.
The question whether epidermal growth factor (EGF)-induced receptor endocytosis requires the prior autophosphorylation via the EGF receptor (EGFR) kinase domain has been a matter of long-standing debate. In the airway epithelial cell line NCI-H292, the EGFR kinase domain inhibitor BIBW 2948 BS was found to inhibit both autophosphorylation and subsequent internalization of the endogenous EGFR with similar IC₅₀ values. Applying an ex vivo EGFR internalization assay in a clinical study, the in vivo effect of inhalatively administered BIBW 2948 BS was determined directly at the targeted receptor in airway tissues from COPD patients. In these experiments, the in vivo inhibition of the EGFR kinase domain prevented the EGF-induced internalization of EGFR.
表皮生长因子（EGF）诱导的受体内吞作用是否需要 EGF 受体（EGFR）激酶结构域的磷酸化一直是一个长期存在的争论问题。在气道上皮细胞系 NCI-H292 中，发现 EGFR 激酶结构域抑制剂 BIBW 2948 BS 可抑制内源性 EGFR 的自身磷酸化及其随后的内化，其 IC₅₀ 值相似。在一项临床研究中应用 EGFR 内化的体外测定法，直接在 COPD 患者气道组织中的靶向受体中确定吸入给予 BIBW 2948 BS 的体内作用。在这些实验中，EGFR 激酶结构域的体内抑制作用阻止了 EGF 诱导的 EGFR 内化。
