In vivo inhibition of epidermal growth factor receptor autophosphorylation prevents receptor internalization

被引：2

作者：

Wolff, Michael ^{[1
]}

Tetzlaff, Kay ^{[2
]}

Nivens, Michael C. ^{[2
]}

Schneider, Franz-Josef ^{[3
]}

Jung, Birgit ^{[3
]}

Hohlfeld, Jens ^{[4
]}

Heilker, Ralf ^{[1
]}

机构：

[1] Boehringer Ingelheim GmbH & Co KG, Dept Lead Discovery, D-88397 Biberach, Germany

[2] Boehringer Ingelheim Pharmaceut Inc, Dept Clin Operat Resp, Ridgefield, CT 06877 USA

[3] Boehringer Ingelheim GmbH & Co KG, Dept Pulm Dis Res, D-88397 Biberach, Germany

[4] Fraunhofer Inst Toxicol & Expt Med ITEM, D-30625 Hannover, Germany

来源：

EXPERIMENTAL CELL RESEARCH | 2011年 / 317卷 / 01期

关键词：

Autophosphorylation; Epidermal growth factor receptor; Fluorescence microscopy; Image analysis; Internalization; EGF RECEPTOR; TYROSINE KINASE; MUCIN SYNTHESIS; ENDOCYTOSIS; PHOSPHORYLATION; IDENTIFICATION; RECRUITMENT; ACTIVATION; PATHWAYS; CLATHRIN;

D O I：

10.1016/j.yexcr.2010.09.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2010 Elsevier Inc All rights reserved

引用

页码：42 / 50

页数：9

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