scholarly journals STAM Proteins Bind Ubiquitinated Proteins on the Early Endosome via the VHS Domain and Ubiquitin-interacting Motif

2003 ◽  
Vol 14 (9) ◽  
pp. 3675-3689 ◽  
Author(s):  
Emi Mizuno ◽  
Kensuke Kawahata ◽  
Masaki Kato ◽  
Naomi Kitamura ◽  
Masayuki Komada
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Binding Activity ◽  
Early Endosome ◽  
Ubiquitinated Proteins ◽  
Ubiquitin Binding ◽  
Cargo Proteins ◽  
Epidermal Growth ◽  
Vhs Domain ◽  
Hepatocyte Growth

Conjugation with ubiquitin acts as a sorting signal for proteins in the endocytic and biosynthetic pathways at the endosome. Signal-transducing adaptor molecule (STAM) proteins, STAM1 and STAM2, are associated with hepatocyte growth factor-regulated substrate (Hrs) but their function remains unknown. Herein, we show that STAM proteins bind ubiquitin and ubiquitinated proteins and that the tandemly located VHS (Vps27/Hrs/STAM) domain and ubiquitin-interacting motif serve as the binding site(s). STAM proteins colocalize with Hrs on the early endosome. Overexpression of STAM proteins, but not their mutants lacking the ubiquitin-binding activity, causes the accumulation of ubiquitinated proteins and ligand-activated epidermal growth factor receptor on the early endosome. These results suggest that through interaction with ubiquitinated cargo proteins on the early endosome via the VHS domain and ubiquitin-interacting motif, STAM proteins participate in the sorting of cargo proteins for trafficking to the lysosome.

scholarly journals Distinct Roles for Tsg101 and Hrs in Multivesicular Body Formation and Inward Vesiculation

2006 ◽  
Vol 17 (8) ◽  
pp. 3469-3483 ◽  
Author(s):  
M. Razi ◽  
C. E. Futter
Keyword(s):  
Growth Factor ◽  
Mammalian Cells ◽  
Susceptibility Gene ◽  
Growth Factor Receptor ◽  
Multivesicular Body ◽  
Early Endosome ◽  
Endosomal Sorting ◽  
Epidermal Growth ◽  
Tumor Susceptibility Gene ◽  
Hepatocyte Growth

In mammalian cells, epidermal growth factor (EGF) stimulation promotes multivesicular body (MVB) formation and inward vesiculation within MVB. Annexin 1 is required for EGF-stimulated inward vesiculation but not MVB formation, demonstrating that MVB formation (the number of MVBs/unit cytoplasm) and inward vesiculation (the number of internal vesicles/MVB) are regulated by different mechanisms. Here, we show that EGF-stimulated MVB formation requires the tumor susceptibility gene, Tsg101, a component of the ESCRT (endosomal sorting complex required for transport) machinery. Depletion of Tsg101 potently inhibits EGF degradation and MVB formation and causes the vacuolar domains of the early endosome to tubulate. Although Tsg101 depletion inhibits MVB formation and alters the morphology of the early endosome in unstimulated cells, these effects are much greater after EGF stimulation. In contrast, depletion of hepatocyte growth factor receptor substrate (Hrs) only modestly inhibits EGF degradation, does not induce tubulation of the early endosome, and causes the generation of enlarged MVBs that retain the ability to fuse with the lysosome. Together, these results indicate that Tsg101 is required for the formation of stable vacuolar domains within the early endosome that develop into MVBs and Hrs is required for the accumulation of internal vesicles within MVBs and that both these processes are up-regulated by EGF stimulation.

scholarly journals Hepatocyte Growth Factor Induces Resistance to Anti-Epidermal Growth Factor Receptor Antibody in Lung Cancer

2012 ◽  
Vol 7 (2) ◽  
pp. 272-280 ◽  
Author(s):  
Tadaaki Yamada ◽  
Shinji Takeuchi ◽  
Kenji Kita ◽  
Hideaki Bando ◽  
Takahiro Nakamura ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Antibody ◽  
Epidermal Growth ◽  
Hepatocyte Growth
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