Format

Send to

Choose Destination
Nat Commun. 2014 May 19;5:3907. doi: 10.1038/ncomms4907.

Receptor tyrosine kinase c-Met controls the cytoskeleton from different endosomes via different pathways.

Author information

1
1] Centre for Tumour Biology, Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK [2] Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
2
1] Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK [2] Division of Cancer Studies, King's College School of Medicine, Guy's Hospital, Thomas Street, London SE1 9RT, UK.
3
Centre for Tumour Biology, Barts Cancer Institute-a Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.

Abstract

Receptor tyrosine kinases (RTKs) are increasingly recognized as having the capacity to signal post-internalization. Signalling outputs and/or duration, and subsequent cellular outcome, are thought to be distinct when emanating from endosomes compared with those from the plasma membrane. Here we show, in invasive, basal-like human breast cell models, that different mechanisms are engaged by the RTK c-Met in two different endosomes to control the actin cytoskeleton via the key migratory signal output Rac1. Despite an acute activation of Rac1 from peripheral endosomes (PEs), c-Met needs to traffic to a perinuclear endosome (PNE) to sustain Rac1 signalling, trigger optimal membrane ruffling, cell migration and invasion. Unexpectedly, in the PNE but not in the PE, PI3K and the Rac-GEF Vav2 are required. Thus we describe a novel endosomal signalling mechanism whereby one signal output, Rac1, is stimulated through distinct pathways by the same RTK depending on which endosome it is localized to in the cell.

PMID:
24835487
DOI:
10.1038/ncomms4907
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center