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Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins

Oncogene volume 18, pages 1165–1176 (1999)Cite this article

Abstract

Bcr-Abl plays a critical role in the pathogenesis of Philadelphia chromosome-positive leukemia. Although a large number of substrates and interacting proteins of Bcr-Abl have been identified, it remains unclear whether Bcr-Abl assembles multi-protein complexes and if it does where these complexes are within cells. We have investigated the localization of Bcr-Abl in 32D myeloid cells attached to the extracellular matrix. We have found that Bcr-Abl displays a polarized distribution, co-localizing with a subset of filamentous actin at trailing portions of migrating 32D cells, and localizes on the cortical F-actin and on vesicle-like structures in resting 32D cells. Deletion of the actin binding domain of Bcr-Abl (Bcr-Abl-AD) dramatically enhances the localization of Bcr-Abl on the vesicle-like structures. These distinct localization patterns of Bcr-Abl and Bcr-Abl-AD enabled us to examine the localization of Bcr-Abl substrate and interacting proteins in relation to Bcr-Abl. We found that a subset of biochemically defined target proteins of Bcr-Abl redistributed and co-localized with Bcr-Abl on F-actin and on vesicle-like structures. The co-localization of signaling proteins with Bcr-Abl at its sites of localization supports the idea that Bcr-Abl forms a multi-protein signaling complex, while the polarized distribution and vesicle-like localization of Bcr-Abl may play a role in leukemogenesis.

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Acknowledgements

We thank Drs A Bouton, R Salgia, M Lasanti and M Zerial for providing anti-p130Cas, -Crkl, -caveolin, and -Rab7 antibodies, respectively, and X Zhang and A Gross for technical help and critical reading of the manuscript. This work was supported by National Cancer Institute grant CA68008 (to RR). RR is a recipient of American Cancer Society Junior Faculty Research Award.

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  1. Rosenstiel Basic Medical Sciences Research Center and Department of Biology, Brandeis University, Waltham, 02254-9110, Massachusetts, USA

    Paris A Skourides, Samanthi A Perera & Ruibao Ren

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Skourides, P., Perera, S. & Ren, R. Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins. Oncogene 18, 1165–1176 (1999). https://doi.org/10.1038/sj.onc.1202407

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