cbl-b inhibits epidermal growth factor receptor signaling

被引:104
|
作者
Ettenberg, SA
Keane, MM
Nau, MM
Frankel, M
Wang, LM
Pierce, JH
Lipkowitz, S [1 ]
机构
[1] USN Hosp, NCI, Med Branch, Dept Genet, Bethesda, MD 20889 USA
[2] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
[3] NCI, Mol & Cellular Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA
关键词
cbl proteins; EGF receptor; signal transduction;
D O I
10.1038/sj.onc.1202499
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
The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR),vas studied and compared with c-cbl, We demonstrate in vivo, that chl-b, like c-cbl, is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl proteins can bind to the Grb2 adaptor protein, To investigate the functional role of chi proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells overexpressing the EGFR (32D/EGFR), This cell line is absolutely dependent on exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b showed markedly inhibited growth in EGF compared to c-cbl transfectants and vector controls, This growth inhibition by cbl-b was the result of a dramatic increase in the number of cells undergoing apoptosis, Consistent with this finding, chl-b overexpression markedly decreased the amplitude and duration of AKT activation upon EGF stimulation compared to either vector controls or c-cbl overexpressing cells. In addition, the duration of EGF mediated MAP kinase and Jun kinase activation in cells overespressing cbl-b is shortened. These data demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl have distinct roles in EGF mediated signaling.
引用
收藏
页码:1855 / 1866
页数:12
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