Abstract:
:Mitogenic tyrosine kinase receptors such as the EGFR (epidermal growth factor receptor) are endocytosed once they are activated at the cell surface. After reaching the early endosome, they are ubiquitinated within their cytosolic domain and are consequently sorted away from recycling receptors. They are then incorporated into intraluminal vesicles within the MVB (multivesicular body) en route to the lysosome, where they are degraded. MVB formation requires the stabilization of the vacuolar domain of the early endosome, the segregation of degradative cargo within this domain (with subsequent incorporation of receptors such as EGFR into intraluminal vesicles) and the physical separation and movement of this domain away from the tubular regions of the early endosome. How these different aspects of MVB biogenesis are coupled is unknown, but ESCRTs (endosomal sorting complexes required for transport) have been identified as key molecular players in driving mitogenic receptor sequestration and formation of intraluminal vesicles. The present review summarizes recent findings within the field and from our laboratory regarding the detailed function of ESCRTs and associated proteins in driving the ubiquitin-dependent sorting of EGFR and in maintaining the domain organization of the early endosome.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Woodman Pdoi
10.1042/BST0370146subject
Has Abstractpub_date
2009-02-01 00:00:00pages
146-50issue
Pt 1eissn
0300-5127issn
1470-8752pii
BST0370146journal_volume
37pub_type
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journal_title:Biochemical Society transactions
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journal_title:Biochemical Society transactions
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journal_title:Biochemical Society transactions
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更新日期:2010-08-01 00:00:00
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