Analysis of trk A and p53 association

FEBS Letters

Rowe, Janice¹  Browes, Clare²  Brown, Anna²  Montano, Ximena² 

[1]Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

[2]Cancer Research Unit, Medical School, Framlington Place, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK

关键词: trk A;    c-abl;    p53 mutant;    Association;    Mapping;   

DOI  :  10.1016/S0014-5793(01)02429-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

trk A tyrosine kinase (the high affinity receptor for nerve growth factor) binds to the p53 tumour suppressor protein in vitro and in vivo. Our aim was to determine which regions of p53 are involved in trk A association. In vitro binding experiments using baculovirus expressed trk A and in vitro transcribed and translated C-terminus p53 deletion mutants show amino acids 327–338 critical for association. Also, analysis with mutants at the N-terminus, conserved regions II, III, IV and V or amino acid positions 173, 175, 181, 248 and 249 (which are amino acids frequently mutated in a variety of neoplasms and transformed cell lines), show that these sites are not involved in trk A binding. Importantly, similar results are obtained after immunoprecipitation of lysates from p53 negative fibroblasts expressing trk A and the above p53 mutant proteins. These data suggest that the amino-terminus of the oligomerisation domain of p53 is involved in p53/trk A association.

【 授权许可】

Unknown