2004
DOI: 10.1091/mbc.e04-06-0446
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Regulation of Epidermal Growth Factor Receptor Degradation by Heterotrimeric Gαs Protein

Abstract: Heterotrimeric G proteins have been implicated in the regulation of membrane trafficking, but the mechanisms involved are not well understood. Here, we report that overexpression of the stimulatory G protein subunit (Gαs) promotes ligand-dependent degradation of epidermal growth factor (EGF) receptors and Texas Red EGF, and knock-down of Gαs expression by RNA interference (RNAi) delays receptor degradation. We also show that Gαs and its GTPase activating protein (GAP), RGS-PX1, interact with hepatocyte growth … Show more

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Cited by 58 publications
(88 citation statements)
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“…The change in megalin and ARH localization in mutant cells indicates a shift in its distribution to the inside of the cell (presumably to recycling endosomes) and suggests defects in their recycling to the plasma membrane. The implication that RGS-PX1͞SNX13 is involved in receptor recycling adds a new dimension to the role of RGS-PX1͞SNX13 in receptor degradation previously demonstrated by using cultured cells and ectopic expression (10). Another striking feature in the Snx13-null VYS endoderm is the appearance of autophagic vacuoles which most likely reflects a deficiency in the supply of nutrients from endocytic uptake and͞or lysosomal degradation in these cells, as autophagy represents a major cellular response to nutrient deprivation (18).…”
Section: Discussionmentioning
confidence: 83%
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“…The change in megalin and ARH localization in mutant cells indicates a shift in its distribution to the inside of the cell (presumably to recycling endosomes) and suggests defects in their recycling to the plasma membrane. The implication that RGS-PX1͞SNX13 is involved in receptor recycling adds a new dimension to the role of RGS-PX1͞SNX13 in receptor degradation previously demonstrated by using cultured cells and ectopic expression (10). Another striking feature in the Snx13-null VYS endoderm is the appearance of autophagic vacuoles which most likely reflects a deficiency in the supply of nutrients from endocytic uptake and͞or lysosomal degradation in these cells, as autophagy represents a major cellular response to nutrient deprivation (18).…”
Section: Discussionmentioning
confidence: 83%
“…We showed previously that RGS-PX1͞SNX13 is localized in early endosomes, and overexpression of RGS-PX1͞SNX13 delays the degradation of epidermal growth factor receptor, probably at the steps of endosome sorting and lysosomal targeting (8). More recently, we found that RGS-PX1 and G␣s form a complex with Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate), a critical component of the endosomal sorting machinery that targets ubiquitinated membrane proteins for sequestration into multivesicular bodies and subsequent degradation in lysosomes (10). These studies using cultured mammalian cells demonstrated that RGS-PX1 plays an important role in the regulation of endocytic trafficking.…”
mentioning
confidence: 76%
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“…Invagination of the endosomal membrane and delivery of sequestered receptors into the lumen of the MVB is accompanied by receptor deubiquitination and disassembly of the ESCRT complex (11,12). The ESCRT machinery, first identified in yeast as class E Vps (vacuolar protein sorting) mutants (13) and highly conserved among eukaryotic cells (14), is important in targeting EGFR into the lumen of the MVB (15,16). Substantial progress has been made in identifying the molecular mechanisms involved (12,17).…”
mentioning
confidence: 99%
“…Fibroblast cell lines derived from STAM1 and STAM2 double knock-out mice display delayed EGFR degradation (24). Hrs-STAM complex is required for the recruitment of ESCRT-1 (16,25), an early event in MVB formation (26).…”
mentioning
confidence: 99%