Internalization of EGF receptor following lipid rafts disruption in keratinocytes is delayed and dependent on p38 MAPK activation

Journal of Cellular Physiology
Sylviane LambertYves Poumay

Abstract

The receptor for epidermal growth factor (EGF) plays an important role in epidermal keratinocytes and is known to move out of lipid raft after cholesterol depletion, leading to ligand-independent activation. Accumulation of evidence indicates the ability of EGF receptor (EGFR) to undergo internalization without participation of the ligand under the control of p38 MAPK during stress conditions. Since cholesterol depletion using methyl-beta-cyclodextrin is known to induce ligand-independent activation of EGFR in keratinocytes, we investigated by confocal microscopy and ligand-binding tests the processing and localization of EGFR following lipid raft disruption. Here, we report the dimerization and the slow internalization of the receptor accompanied by the delayed phosphorylation of tyrosine 1068 and its degradation by the proteasome. We also demonstrate the involvement of p38 MAPK during the process of internalization, which can be considered as a protective response to stress. Moreover, cholesterol-depleted keratinocytes recover their ability to proliferate during the recovery period that follows lipid raft disruption.

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Citations

Dec 30, 2009·Archives of Dermatological Research·Sylviane LambertYves Poumay
Jan 15, 2010·Molecular & Cellular Proteomics : MCP·Thiemo B SchreiberHenrik Daub
Mar 26, 2013·The Journal of Clinical Investigation·Robert M HarmonKathleen J Green
Feb 19, 2009·Journal of Neuroscience Research·M E EvangelopoulosA Krüttgen
Dec 1, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jeong Hee JeonYoon Soo Chang
Oct 22, 2016·Biochimica Et Biophysica Acta·R Ariel Igal
Nov 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jing Wang, Robert K Yu
May 28, 2019·Frontiers in Cell and Developmental Biology·Michael G SugiyamaCostin N Antonescu
Mar 21, 2019·Cancer Research·Guizhong ZhangXiaochun Wan
May 8, 2020·Biochimica Et Biophysica Acta. Biomembranes·Stephanie E Zimmer, Andrew P Kowalczyk
Feb 11, 2010·Current Opinion in Clinical Nutrition and Metabolic Care

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