P210 BCR-ABL is complexed to P160 BCR and ph-P53 proteins in K562 cells.
The BCR gene (Groffen et al., 1984) plays a critical role in the pathogenesis of human leukemias that involve the Philadelphia chromosome (Ph1) (Rowley, 1973; Nowell & Hungerford, 1960). Cells containing the Ph1 contain a chimeric gene formed from the fusion of BCR (Collins et al., 1987; Lifshitz et al. 1988) and ABL genes that results from the reciprocal translocation of segments of chromosomes 9 and 22 (Shtivelman et al., 1985). The product of this chimera is a 210 kDa protein, termed P210 BCR-ABL, that possesses an activated tyrosine kinase activity (Konopka et al., 1984; Kloetzer et al., 1985). Studies using long-term marrow culture systems and retrovirus-mediated gene transfer have documented that P210 BCR-ABL can stimulate the growth of immature hematopoietic precursor cell types (McLaughlin et al., 1987; Young & Witte, 1984). We have previously reported that P210 BCR-ABL exists in cytoplasmic complexes in association with a 53 kDa protein termed ph-P53 (Maxwell et al., 1987; Li et al. 1988). Similarly, BCR proteins have been found in cytoplasmic complexes containing ph-P53 in cells lacking the Ph1 (Li et al., 1989). These BCR protein complexes possess an associated ser/thr protein kinase activity. In this same study, we found that P210-containing complexes phosphorylate BCR proteins on tyrosine residues in vitro (Li et al., 1989). We now present results which demonstrate that P210 BCR-ABL is tightly associated with P160 BCR and ph-P53 proteins in cytoplasmic complexes from cells containing the Ph1.
Campbell
M L
ML
Department of Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Li
W
W
Arlinghaus
R B
RB
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism*; D010677:Philadelphia Chromosome; D010750:Phosphoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr; D016159:Tumor Suppressor Protein p53
D000912:Antibodies, Neoplasm; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr