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
相关论文
共 45 条
  • [21] UV activates growth factor receptors via reactive oxygen intermediates
    Huang, RP
    Wu, JX
    Fan, Y
    Adamson, ED
    [J]. JOURNAL OF CELL BIOLOGY, 1996, 133 (01) : 211 - 220
  • [22] IMMUNOSTAINING OF HUMAN AUTOPSY AORTAS WITH ANTIBODIES TO MODIFIED APOLIPOPROTEIN-B AND APOPROTEIN(A)
    JURGENS, G
    CHEN, Q
    ESTERBAUER, H
    MAIR, S
    LEDINSKI, G
    DINGES, HP
    [J]. ARTERIOSCLEROSIS AND THROMBOSIS, 1993, 13 (11): : 1689 - 1699
  • [23] KASLAUKAS A, 1994, CURR OPIN GENE DEV, V4, P5
  • [24] THE B-ISOFORM OF THE INSULIN-RECEPTOR SIGNALS MORE EFFICIENTLY THAN THE A-ISOFORM IN HEPG2 CELLS
    KOSAKI, A
    PILLAY, TS
    XU, L
    WEBSTER, NJG
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (35) : 20816 - 20823
  • [25] LYSOPHOSPHATIDYLCHOLINE TRANSCRIPTIONALLY INDUCES GROWTH-FACTOR GENE-EXPRESSION IN CULTURED HUMAN ENDOTHELIAL-CELLS
    KUME, N
    GIMBRONE, MA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) : 907 - 911
  • [26] THE SH2 AND SH3 DOMAIN-CONTAINING NCK PROTEIN IS ONCOGENIC AND A COMMON TARGET FOR PHOSPHORYLATION BY DIFFERENT SURFACE-RECEPTORS
    LI, W
    HU, P
    SKOLNIK, EY
    ULLRICH, A
    SCHLESSINGER, J
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (12) : 5824 - 5833
  • [27] THE SH2 AND SH3 DOMAIN CONTAINING PROTEIN GRB2 LINKS RECEPTOR TYROSINE KINASES TO RAS SIGNALING
    LOWENSTEIN, EJ
    DALY, RJ
    BATZER, AG
    LI, W
    MARGOLIS, B
    LAMMERS, R
    ULLRICH, A
    SKOLNIK, EY
    BARSAGI, D
    SCHLESSINGER, J
    [J]. CELL, 1992, 70 (03) : 431 - 442
  • [28] THE TYROSINE PHOSPHORYLATED CARBOXYTERMINUS OF THE EGF RECEPTOR IS A BINDING-SITE FOR GAP AND PLC-GAMMA
    MARGOLIS, B
    LI, N
    KOCH, A
    MOHAMMADI, M
    HURWITZ, DR
    ZILBERSTEIN, A
    ULLRICH, A
    PAWSON, T
    SCHLESSINGER, J
    [J]. EMBO JOURNAL, 1990, 9 (13) : 4375 - 4380
  • [29] APPEARANCE OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR IN WOUND FLUID AS A RESPONSE TO INJURY
    MARIKOVSKY, M
    BREUING, K
    LIU, PY
    ERIKSSON, E
    HIGASHIYAMA, S
    FARBER, P
    ABRAHAM, J
    KLAGSBRUN, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (09) : 3889 - 3893
  • [30] SH2 DOMAINS OF THE P85-ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE REGULATE BINDING TO GROWTH-FACTOR RECEPTORS
    MCGLADE, CJ
    ELLIS, C
    REEDIJK, M
    ANDERSON, D
    MBAMALU, G
    REITH, AD
    PANAYOTOU, G
    END, P
    BERNSTEIN, A
    KAZLAUSKAS, A
    WATERFIELD, MD
    PAWSON, T
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (03) : 991 - 997