Truncated adenomatous polyposis coli (APC) tumour suppressor protein can undergo tyrosine phosphorylation

Numerous mutations in the adenomatous polyposis coli (APC) gene have been d escribed in colorectal cancer. The vast majority introduce nonsense codons leading to the production of truncated N-terminal APC fragments. Mutations occurring before APC codon 158, have been associated with an attenuated for m of familial adenomatous polyposis whereas those occurring at codon 168 or beyond lead to the characteristic form of the disease. These 10 amino acid residues of APC contain a YYAQ motif which appears to constitute a potenti al SH2 binding domain similar to a sequence present in tyrosine kinase rece ptors that activate STAT 3 when phosphorylated. We have expressed a recombi nant, N-terminal APC fragment in bacterial cells, and shown that it can ind eed undergo tyrosine phosphorylation in this domain. We used site-directed mutagenesis to confirm the specificity of the reaction. These observations raise the possibility that tyrosine phosphorylation may be another mechanis m involved in controlling APC function. (C) 2000 Elsevier Science Ltd. All rights reserved.