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Identification of proteolytic fragments from ErbB-2 that induce apoptosis

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Abstract

The receptor tyrosine kinase ErbB-2 plays an important role in cell proliferation and differentiation as well as oncogenesis. We have found that ErbB-2 kinase domain fragmentation is important for the induction of apoptosis. Exogenous expression of peptides derived from the ErbB-2 kinase domain induces cells death with the hallmarks of apoptosis. In contrast, transfection of the ErbB-2 carboxy-terminal domain did not induce apoptosis. We have identified a 37-residue segment from the ErbB-2 kinase N-terminal lobe that can strongly induce apoptosis in transfected cells. Cell death was not blocked by the pan-caspase inhibitor z-VAD-FMK. Similar fragments derived from several other receptor tyrosine kinases also induce cell death. These data imply that proteolytic fragmentation of tyrosine kinases liberates apoptotic fragments that can accelerate cell death.

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Acknowledgements

We are grateful to Catherine Alford and Vanderbilt University Flow Cytometry Core Facility for technical support. The support of the Department of Defense Idea Award Grant DAMD 17-00-1-0483, grant of the Vanderbilt Ingram Cancer Center P30 CA68485 and the Vanderbilt Diabetes Center P30 DK20593 for core facility support are acknowledged.

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Authors and Affiliations

  1. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 37232-0146, USA

    Oleg Tikhomirov & Graham Carpenter

  2. Division of Hematology/Oncology, Vanderbilt University School of Medicine, Nashville, TN, 37232-0146, USA

    Mikhail Dikov

  3. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232-0146, USA

    Mikhail Dikov & Graham Carpenter

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  1. Oleg Tikhomirov
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  2. Mikhail Dikov
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  3. Graham Carpenter
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Correspondence to Graham Carpenter.

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Tikhomirov, O., Dikov, M. & Carpenter, G. Identification of proteolytic fragments from ErbB-2 that induce apoptosis. Oncogene 24, 3906–3913 (2005). https://doi.org/10.1038/sj.onc.1208534

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  • DOI: https://doi.org/10.1038/sj.onc.1208534

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