Tyrosine phosphorylation of P160 BCR by P210 BCR-ABL.
It is well established that the chimeric BCR-ABL gene formed by joining parts of the BCR and ABL genes plays a key role in the pathogenesis of Philadelphia (Ph) chromosome-positive leukemias. We report that simultaneous expression of P210 BCR-ABL and P160 BCR in simian COS-1 cells yielded stable complexes of these two proteins, and induced phosphorylation of P160 BCR on tyrosine residues in vivo. Tyrosine phosphorylation of a deletion mutant encoding 553 amino acids of BCR N-terminal sequences was also detected when it was coexpressed with P210 BCR-ABL. We propose that tyrosine phosphorylation of P160 BCR by P210 BCR-ABL and their stable physical interaction may perturb normal BCR functions and that these alterations are directly involved in the pathologic processes found in Ph chromosome-associated leukemias.
Lu
D
D
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Liu
J
J
Campbell
M
M
Guo
J Q
JQ
Heisterkamp
N
N
Groffen
J
J
Canaani
E
E
Arlinghaus
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr; D014407:Tumor Cells, Cultured; 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