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cbl-3: a new mammalian cbl family protein

Oncogene volume 18, pages 3365–3375 (1999)Cite this article

Abstract

We have cloned a new human gene, cbl-3, which encodes a protein with marked homology to the cbl family of proteins. The predicted protein encoded by this gene retains the conserved phosphotyrosine binding domain (PTB) in the N-terminal and the zinc finger but is significantly shorter (MW 52.5 kDa) than the other mammalian cbl proteins. The protein lacks the extensive proline rich domain and leucine zipper seen in c-cbl and cbl-b and structurally most resembles the C. elegans and Drosophila cbl proteins. The gene is ubiquitously expressed with highest expression in the aerodigestive tract, prostate, adrenal gland, and salivary gland. The protein is phosphorylated and recruited to the EGFR upon EGF stimulation and inhibits EGF stimulated MAP kinase activation. In comparison to the other mammalian cbl proteins (e.g. cbl-b), cbl-3 interacts with a restricted range of proteins containing Src Homology 3 regions. An alternatively spliced form of the cbl-3 protein was also identified which deletes a critical region of the PTB domain and which does not interact with the EGFR nor inhibit EGF stimulated MAP kinase activation. These data demonstrate that cbl-3, a novel mammalian cbl protein, is a regulator of EGFR mediated signal transduction.

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Authors and Affiliations

  1. Genetics Department, Medicine Branch, National Cancer Institute, Bethesda Naval Hospital, Bethesda, 20889, Maryland, USA

    Maccon M Keane, Seth A Ettenberg, Marion M Nau, Priya Banerjee, Mauricio Cuello & Stan Lipkowitz

  2. Departments of Medical Biophysics and Immunology, Amgen Institute/Ontario Cancer Institute, University of Toronto, Toronto/Ontario, Canada

    Josef Penninger

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  1. Maccon M Keane
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  2. Seth A Ettenberg
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Keane, M., Ettenberg, S., Nau, M. et al. cbl-3: a new mammalian cbl family protein. Oncogene 18, 3365–3375 (1999). https://doi.org/10.1038/sj.onc.1202753

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