Activation of EGF receptor by oxidized LDL

被引:127
作者
Suc, I
Meilhac, O
Lajoie-Mazenc, I
Vandaele, J
Jürgens, G
Salvayre, R
Nègre-Salvayre, A
机构
[1] CHU Rangueil, INSERM, U466, IFR 31, F-31403 Toulouse 4, France
[2] CHU Rangueil, Inst Louis Bugnard, Dept Biochem, F-31403 Toulouse, France
[3] Karl Franzens Univ Graz, Inst Med Biochem, Graz, Austria
关键词
signaling; 4-hydroxynonenal; tyrosine phosphorylation;
D O I
10.1096/fasebj.12.9.665
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oxidized low density lipoproteins (oxLDL) are thought to play a major role: in atherosclerosis, OxLDL exhibit a wide variety of biological effects resulting from their ability to interfere with intracellular signaling, The cellular targets and primary signaling events of oxLDL are unknown. We report that oxLDL elicit, in intact cells, tyrosine phosphorylation of the epithelial growth factor receptor (EGFR) and activation of its signaling pathway. This activation triggered by oxLDL was associated with derivatization of reactive amino groups of EGFR and was mimicked by 4-hydroxynonenal (4-HNE, a major lipid peroxidation product of oxLDL), Immunopurified EGFR was derivatized and activated in vitro by oxLDL lipid extracts and 4-HNE, thus indicating that 1) EGFR may be a primary target of oxidized lipids and 2) EGFR derivatization may be associated with activation. The reported data suggest that EGFR acts as a sensor for oxidized lipids. We therefore propose a novel concept of the mechanism by which oxidized lipids (contained in oxLDL or more generally produced during oxidative stress) are able to activate receptor tyrosine kinase and subsequent signaling pathways, resulting finally in a gain of function.
引用
收藏
页码:665 / 671
页数:7
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