Cytoplasmic and nuclear localization of the 130 and 160 kDa Bcr proteins.
Formation of the Bcr-Abl chimeric protein is the molecular hallmark of Philadelphia-positive leukemia. Normal Bcr is a complex protein which has been found in the cytoplasm, has serine kinase activity, and has been implicated in cellular signal transduction. However, we have recently demonstrated that Bcr can also associate with condensed chromatin. Since two major Bcr proteins have been characterized (p160Bcr and p130Bcr), we sought to determine if different forms of Bcr localized to the nucleus vs the cytoplasm. Metabolic labeling and Western blotting experiments were performed using nuclear and cytoplasmic extracts of three human Philadelphia-negative leukemia/lymphoma cell lines (KG-1, HL-60, and Jurkat). Both methodologies showed that p160Bcr and p130Bcr localized to the cytoplasm, but the p130 form predominated in the nucleus. These results suggest that Bcr serves both nuclear and cytoplasmic functions, and that different forms of Bcr may be preferentially involved in these distinct activities.
Laurent
E
E
Department of Bioimmunotherapy, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Talpaz
M
M
Wetzler
M
M
Kurzrock
R
R
D000208:Acute Disease; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry*; D003593:Cytoplasm / Q000737:chemistry*; D018922:HL-60 Cells / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry / Q000648:ultrastructure; D007951:Leukemia, Myeloid / Q000473:pathology; D016253:Microscopy, Immunoelectron; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis / Q000737:chemistry; D020033:Protein Isoforms / Q000032:analysis* / Q000737:chemistry; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D051562:Proto-Oncogene Proteins c-bcr; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000648:ultrastructure
D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr