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Down-regulation of MET, the receptor for hepatocyte growth factor

Oncogene volume 20, pages 2761–2770 (2001)Cite this article

Abstract

The ligand-dependent degradation of activated tyrosine kinase receptors provides a means by which mitogenic signalling can be attenuated. In many cell types the ligand-dependent degradation of the tyrosine kinase receptor Met is completely dependent on the activity of the 26S proteasome (Jeffers et al., 1997b). We now show that degradation also requires trafficking to late endosomal compartments and the activity of acid dependent proteases as determined by the effects of a dominant negative form of dynamin (K44A) and a vacuolar-ATPase inhibitor, concanamycin. We show that in the presence of the proteasome inhibitor lactacystin, Met fails to redistribute from the plasma membrane to intracellular compartments. This observation is most consistent with the interpretation that proteasome activity is required for Met internalization and only indirectly for its degradation.

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Acknowledgements

Dean Hammond is the recipient of a Wellcome Trust prize studentship. Sylvie Urbé is supported by a fellowship from the North West Cancer Research Fund. We thank members of the Haematology Department, University of Liverpool for allowing us to use their con-focal microscope. We also thank Jean Gruenberg and Harry Mellor for provision of antibodies and Dave Fernig for EGF.

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Authors and Affiliations

  1. Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

    Dean E Hammond, Sylvie Urbé & Michael J Clague

  2. Van Andel Research Institute, 333 Bostwick Northeast, Grand Rapids, 49503, Michigan, MI, USA

    George F Vande Woude

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Hammond, D., Urbé, S., Vande Woude, G. et al. Down-regulation of MET, the receptor for hepatocyte growth factor. Oncogene 20, 2761–2770 (2001). https://doi.org/10.1038/sj.onc.1204475

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