Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04626 (
erbB-2
)
5,251
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The endosomal sorting complexes required for transport, ESCRT-I, -II, and -III, are thought to mediate the biogenesis of multivesicular endosomes (MVEs) and endosomal sorting of ubiquitinated membrane proteins. Here, we have compared the importance of the ESCRT-I subunit tumor susceptibility gene 101 (Tsg101) and the ESCRT-III subunit
hVps24
/
CHMP3
for endosomal functions and receptor signaling. Like Tsg101, endogenous
hVps24
localized mainly to late endosomes. Depletion of
hVps24
by siRNA showed that this ESCRT subunit, like Tsg101, is important for degradation of the
epidermal growth factor (EGF) receptor
(EGFR) and for transport of the receptor from early endosomes to lysosomes. Surprisingly, however, whereas depletion of Tsg101 caused sustained EGF activation of the mitogen-activated protein kinase pathway, depletion of
hVps24
had no such effect. Moreover, depletion of Tsg101 but not of
hVps24
caused a major fraction of internalized EGF to accumulate in nonacidified endosomes. Electron microscopy of
hVps24
-depleted cells showed an accumulation of EGFRs in MVEs that were significantly smaller than those in control cells, probably because of an impaired fusion with lyso-bisphosphatidic acid-positive late endosomes/lysosomes. Together, our results reveal functional differences between ESCRT-I and ESCRT-III in degradative protein trafficking and indicate that degradation of the EGFR is not required for termination of its signaling.
...
PMID:The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. 1655 68
