The proto-oncogene c-Cbl is a negative regulator of DNA synthesis initiated by both receptor and cytoplasmic tyrosine kinases

被引:24
作者
Broome, MA
Galisteo, ML
Schlessinger, J
Courtneidge, SA
机构
[1] SUGEN Inc, S San Francisco, CA 94080 USA
[2] NYU Med Ctr, Dept Pharmacol, New York, NY 10016 USA
关键词
c-Cbl; Src; growth-factor-signaling; mitogenesis;
D O I
10.1038/sj.onc.1202873
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
In C, elegans, genetic and biochemical data indicate that the Cbl homolog Sli-1 attenuates Let-23 (EGFR) signaling. To investigate whether c-Cbl might have a role in mammalian growth factor-mediated mitogenic signaling, me microinjected NIH3T3 mouse fibroblasts with expression plasmids encoding wt and G306ECbl (a 'loss of function' mutant identified in C. elegans). We observed inhibition of PDGF BB- and EGF-induced DNA synthesis by wt Cbl but not the mutant. Microinjection of two different affinity purified polyclonal antisera against Cbl boosted a suboptimal PDGF-stimulated mitogenic response. The inhibition of both PDGF BB- and EGF-induced DNA synthesis by,rt Cbl was reversed by co-expression with Myc but not with Fos, DNA synthesis initiated by constitutively activated Src was also blocked by Cbl expression, but curiously by the G306E mutant as well. These data are all consistent with the proposition that Cbl negatively affects mitogenic signaling in mammalian fibroblasts.
引用
收藏
页码:2908 / 2912
页数:5
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