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Specific association of Type I c-Abl with Ran GTPase in lipopolysaccharide-mediated differentiation

Oncogene volume 20, pages 2618–2625 (2001)Cite this article

Abstract

Each of several isoforms of c-Abl may be involved in different biological functions. Type I c-Abl has been shown to be involved in LPS-induced differentiation and Type IV c-Abl, apoptosis. Ran has recently been shown to be involved in LPS endotoxin signal transduction. Here we show that Type I c-Abl associates with Ran. Formation of this complex is specific, as Ran did not associate with the highly homologous Type IV c-Abl isoform. In non-stimulated lymphoid B cells, Type I c-Abl tyrosine kinase is inactive, whereas Type IV kinase is active. Formation of Type I c-Abl/Ran complex and activation of Type I c-Abl kinase activity are LPS dose-dependent. This complex is detectable in B cells of endotoxin-sensitive inbred mice but absent in B cells of endotoxin-resistant mice. These findings therefore suggest that Type I c-Abl and Ran are important targets in lipopolysaccharide-induced biological responses of hematopoietic cells.

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Acknowledgements

We thank Yuan Quan and Hong Chen for discussions, assistance and experimental verification; Dr Mary Moore (Baylor College) for the anti-Ran antibody, and Dr Jean Wang (UCSD) for the 8E9 monoclonal antibody. This work was supported by NIH grants (RO1AI39159 and RO1CA70854) to PMC Wong.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, 19140, Pennsylvania, PA, USA

    Rene Daniel, Siu-Wah Chung & Peter M C Wong

  2. Department of Microbiology and Immunology, Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, 19140, Pennsylvania, PA, USA

    Toby K Eisenstein & Peter M C Wong

  3. Stem Cell Therapeutics, King of Prussia, Pennsylvania, 19406, PA, USA

    Barnet M Sultzer

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  1. Rene Daniel
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Daniel, R., Chung, SW., Eisenstein, T. et al. Specific association of Type I c-Abl with Ran GTPase in lipopolysaccharide-mediated differentiation. Oncogene 20, 2618–2625 (2001). https://doi.org/10.1038/sj.onc.1204361

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