Membrane Regulation of EGFR Signaling by Gangliosides
Xiao-qi Wang, Amy S. Paller*
Identifiers and Pagination:Year: 2009
First Page: 159
Last Page: 162
Publisher Id: TODJ-3-159
Article History:Received Date: 15/05/2009
Revision Received Date: 18/05/2009
Acceptance Date: 18/05/2009
Electronic publication date: 4/11/2009
Collection year: 2009
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Signal transduction is initiated at the cell membrane by the interaction of membrane-anchored receptors (such as growth factors or integrin) with extracellular stimuli (ligands). The availability of these receptors for their ligands and how the activated receptors triggers intracellular signaling cascades are regulated, at least in part, by cholesterol and sphingolipids of the plasma membrane. Gangliosides, sialylated glycosphingolipids, were first shown to regulate epidermal growth factor receptor (EGFR) signal transduction at the membrane level of epithelial cells in the mid-1980’s. Since that time gangliosides have been shown to influence the signaling of a variety of other growth factor receptors. Regulation of signaling by gangliosides involves ganglioside-induced shifts of signaling components at the membrane level that either promote or disrupt signaling complexes. To decrease phosphorylation of the EGFR, ganglioside GM3 has been shown to promote the formation of a complex in which the caveolin-1 and tetraspanin CD82-dependent association of PKC-α with EGFR leads to increased threonine phosphorylation of the EGFR and EGFR internalization, making it unavailable for ligand stimulation. The lack of available EGFR at the membrane may also impact EGFR crosstalk with other signaling pathways, such as those triggered by activation of integrins and the urokinase-like plasminogen activator receptor.