Send to

Choose Destination
Oncogene. 2001 May 17;20(22):2761-70.

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

Author information

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


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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center