BCR-ABL and BCR proteins: biochemical characterization and localization.
The Philadelphia translocation results in the expression of a family of chimaeric proteins in which a portion of the bcr protein is fused to c-abl protein. Using antibodies which recognize different portions of the bcr gene and abl gene products we have compared the normal bcr products with their chimaeric counterparts. We first conclude that the enhanced kinase activity of the rearranged bcr-abl products (p210 and p190) is recovered almost exclusively from the cytosolic fraction. This methodology was confirmed by the demonstration that in cells transformed by the Abelson murine leukemia virus (A-MuLV) the gag-abl kinase activity was recovered equally from the membrane and cytosolic fractions, in agreement with previous studies. To determine whether the distribution of kinase activity reflected the bulk distribution of the bcr-abl proteins, in vivo labeling followed by subcellular fractionation was performed. Both normal bcr proteins and the p210 bcr-abl protein were recovered from the cytosolic fraction with little detectable amounts present in other fractions. In vivo labeling was also used to demonstrate that both normal bcr products and the p210 bcr-abl had a relatively long half-life. It is concluded that bcr-abl products, like normal bcr products are located in the cytosolic fraction.
Dhut
S
S
Medical Oncology Laboratory, St. Bartholomew's Hospital, London, U.K.
Chaplin
T
T
Young
B D
BD
D003600:Cytosol / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr; D014407:Tumor Cells, Cultured / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr