c-abl is involved in the association of p53 and trk A

被引:18
作者
Brown, A
Browes, G
Mitchell, M
Montano, X
机构
[1] Newcastle Univ, Sch Med, Canc Res Unit, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
[2] Imperial Canc Res Fund, London WC2A 3PX, England
关键词
c-abl; phosphorylation; p53 and trk A association; c-abl and trk A association;
D O I
10.1038/sj.onc.1203619
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 p53 tumour suppressor phosphoprotein associates with proteins involved in DNA replication, transcription, cell cycle machinery and regulation of its own expression, Recently it has been shown that p53 can also bind to trk A tyrosine kinase which is the receptor for nerve growth factor (NGF). This study demonstrates that p53 appears to associate with trk A via c-abl, Endogenous c-abl was detected when the trk A and p53 complex was immunoprecipitated from lysates of NGF stimulated NIH3T3 cells expressing trk A or NIH3T3 cells expressing trk A and a temperature sensitive p53 (val 135), Endogenous c-abl and trk A association was observed in NGF stimulated p53 negative fibroblasts transfected with trk A alone; suggesting that c-abl can independently bind to trk A in the absence of p53. Interestingly, association between endogenous p53 and trk A was not detected in NGF stimulated abl negative fibroblasts transfected with trk A or when these cells were exposed to gamma radiation, This result suggests that p53 preferentially binds to trk A in the presence of c-abl and that p53 and trk A do not appear to associate directly even if p53 is activated and its levels increased by gamma radiation, Overall, these data suggest that c-abl is possibly acting as an adaptor or bridge between p53 and trk A.
引用
收藏
页码:3032 / 3040
页数:9
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