title: Tyrosine phosphorylation of P160 BCR by P210 BCR-ABL.
abstract: 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.
authors.affiliation: Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: D
authors.initials: D
authors.lastname: Lu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.forename: J Q
authors.initials: JQ
authors.lastname: Guo
authors.forename: N
authors.initials: N
authors.lastname: Heisterkamp
authors.forename: J
authors.initials: J
authors.lastname: Groffen
authors.forename: E
authors.initials: E
authors.lastname: Canaani
authors.forename: R
authors.initials: R
authors.lastname: Arlinghaus
mesh_terms: 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*
chemical_list: 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