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Analysis of trk A and p53 association
Author(s) -
Browes Clare,
Rowe Janice,
Brown Anna,
Montano Ximena
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02429-2
Subject(s) - trk receptor , amino acid , mutant , immunoprecipitation , biology , in vitro , tyrosine , tropomyosin receptor kinase a , receptor tyrosine kinase , microbiology and biotechnology , in vivo , receptor , biochemistry , genetics , neurotrophin , gene
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.