Cytoplasmic and nuclear localization of the 130 and 160 kDa Bcr proteins

Formation of the Bcr-Abl chimeric protein is the molecular hallmark of Phil adelphia-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 th at Bcr can also associate with condensed chromatin. Since two major Bcr pro teins have been characterized (p160(Bcr) and p130(Bcr)), we sought to deter mine if different forms of Bcr localized to the nucleus vs the cytoplasm. M etabolic labeling and Western blotting experiments were performed using nuc lear and cytoplasmic extracts of three human Philadelphia-negative leukemia /lymphoma cell lines (KG-1, HL-60, and Jurkat). Both methodologies showed t hat p160(Bcr) and p130(Bcr) localized to the cytoplasm, but the p130 form p redominated in the nucleus. These results suggest that Bcr serves both nucl ear and cytoplasmic functions, and that different forms of Bcr may be prefe rentially involved in these distinct activities.