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.
Liu
J
J
Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Campbell
M
M
Guo
J Q
JQ
Lu
D
D
Xian
Y M
YM
Andersson
B S
BS
Arlinghaus
R B
RB
D000818:Animals; D002460:Cell Line; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010449:Peptide Mapping; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr; D011817:Rabbits; D014443:Tyrosine / Q000378:metabolism*
D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr