BCR-ABL tyrosine kinase is autophosphorylated or transphosphorylates P160 BCR on tyrosine predominantly within the first BCR exon.

The role of BCR gene sequences in Philadelphia (Ph) chromosome-positive leukemia is not well understood. Our previous studies demonstrated that P210 BCR-ABL co-precipitates with P160 BCR following immunoprecipitation with antibodies to the C-terminal domain of P160 BCR, sequences lacking in P210 BCR-ABL. We now report that tryptic peptides shared by both P160 BCR and P210 BCR-ABL are phosphorylated on tyrosine in vitro either when using immune complexes containing P160 BCR complexed to BCR-ABL or when P160 BCR is phosphorylated in trans by P210 BCR-ABL immune complexes from cells lacking functional P160 BCR. P185 BCR-ABL produced in a cell line derived from a Ph chromosome-positive acute lymphocytic leukemia patient also co-immunoprecipitated with P160 BCR. As with P210 BCR-ABL, P160 BCR tyrosine phosphopeptides were shared with P185 BCR-ABL, indicating that the major sites of tyrosine phosphorylation in vitro are contained within the first exon of P160 BCR. Similarly, BCR-ABL autophosphorylation was found to occur predominantly at tyrosines within BCR exon 1 sequences. These results raise the possibility that the activated ABL protein kinase of BCR-ABL proteins modulates the putative signal transduction activities of P160 BCR by tyrosine phosphorylation of exon 1 sequences.