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Signalling

Location, location, location

Nature Reviews Cancer volume 11, pages 462–463 (2011)Cite this article

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MET mutants (M1268T and D1246N) that are constitutively active and can transform cells were more highly localized in intracellular compartments of NIH3T3 cells and exhibited increased colocalization with early endosome and recycling endosome markers, as compared with wild-type MET. By contrast, little colocalization of MET mutants was observed with markers of late endosomes or lysosomes. Surface biotinylation and degradation assays further demonstrated constitutive internalization and recycling of the mutants, as well as impaired degradation. Interestingly, inhibition of activation of MET-M1268T by the MET-specific tyrosine kinase inhibitor PHA-665752 (MET-D1246N is insensitive to this inhibitor) did not affect levels of endocytosis.

the increased accumulation and signalling of the MET mutants on endosomes has a direct role in enhancing tumorigenesis.

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ORIGINAL RESEARCH PAPER

  1. Joffre, C. et al. A direct role for Met endocytosis in tumorigenesis. Nature Cell Biol. 5 Jun 2011 (doi:10.1038/ncb2257)

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  1. Sarah Seton-Rogers
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Seton-Rogers, S. Location, location, location. Nat Rev Cancer 11, 462–463 (2011). https://doi.org/10.1038/nrc3096

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