Compartmentalization of epidermal growth factor receptor in liver plasma membrane.
We have investigated epidermal growth factor (EGF)-induced compartmentalization and activation of the EGF receptor (EGFR) in rat liver plasma membrane (PM) raft subfractions prepared by three different biochemical methods previously developed to characterize the composition of membrane rafts. Only detergent-resistant membranes (DRMs) possessed the basic characteristics attributed to membrane rafts. Following the administration of a low dose of EGF (1 microg/100 g BW) the content of EGFR in PM-DRMs did not change significantly; whereas after a higher dose of EGF (5 microg/100 g BW) we observed a rapid and marked disappearance of EGFR (around 80%) from both PM and DRM fractions. Interestingly, following the administration of either a low or high dose of EGF, the pool of EGFR in the PM-DRM fraction became highly Tyr-phosphorylated. In accordance with the higher level of EGFR Tyr-Phosphorylation, EGF induced an augmented recruitment of Grb2 and Shc proteins to PM-DRMs compared with whole PM. Furthermore neither high nor low doses of EGF affected the caveolin content in DRMs and PM. These observations suggest that EGFR located in DRMs are competent for signaling, and non-caveolae PM rafts are involved in the compartmentalization and internalization of the EGFR.
Wang
Ye
Y
Faculty of Medicine, Polypeptide Hormone Laboratory, McGill University, Montreal, Quebec, Canada.
Posner
Barry I
BI
Balbis
Alejandro
A
D000818:Animals; D021941:Caveolae / Q000378:metabolism; D002458:Cell Fractionation / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism*; D003902:Detergents; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
D003902:Detergents; D004815:Epidermal Growth Factor; D066246:ErbB Receptors