|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 51, 49631-49637, December 20, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Cell Biology Program, Memorial Sloan-Kettering Cancer
Center, New York, New York 10021 and Graduate Program in Biochemistry
and Structural Biology, Weill Graduate School of Medical Sciences of
Cornell University, New York, New York 10021
We recently demonstrated that depletion of plasma
membrane cholesterol with methyl-
Cholesterol Depletion from the Plasma Membrane Triggers
Ligand-independent Activation of the Epidermal Growth Factor
Receptor*
-cyclodextrin (MCD) caused
activation of MAPK (Chen, X., and Resh, M. D. (2001) J. Biol. Chem. 276, 34617-34623). MAPK activation was
phosphatidylinositol 3-kinase (PI3K)-dependent and involved
increased tyrosine phosphorylation of the p85 subunit of PI3K. We next
determined whether MCD treatment induced tyrosine phosphorylation of
other cellular proteins. Here we report that cholesterol depletion of
serum-starved COS-1 cells with MCD or filipin caused an increase in
Tyr(P) levels of a 180-kDa protein that was identified as the epidermal
growth factor receptor (EGFR). Cross-linking experiments showed that
MCD induced dimerization of EGFR, indicative of receptor activation.
Reagents that block release of membrane-bound EGFR ligands did not
affect MCD-induced tyrosine phosphorylation of EGFR, indicating that MCD activation of EGFR is ligand-independent. Moreover, MCD treatment resulted in increased tyrosine phosphorylation of EGFR downstream targets and Ras activation. Incubation of cells with the
specific EGFR inhibitor AG4178 blocked MCD-induced phosphorylation of EGFR, SHC, phospholipase C-
, and Gab-1 as well as MAPK
activation. We conclude that cholesterol depletion from the plasma
membrane by MCD causes ligand-independent activation of EGFR,
resulting in MAPK activation by PI3K and Ras-dependent
mechanisms. Moreover, these studies reveal a novel mode of action of
MCD, in addition to its ability to disrupt membrane rafts.
*
This work was supported by National Institutes of Health
Grant GM 57966.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Cell Biology Program,
Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 143, New
York, NY 10021. Tel.: 212-639-2514; Fax: 212-717-3317; E-mail:
m-resh@ski.mskcc.org.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Dhungana, B. A. Merrick, K. B. Tomer, and M. B. Fessler Quantitative Proteomics Analysis of Macrophage Rafts Reveals Compartmentalized Activation of the Proteasome and of Proteasome-mediated ERK Activation in Response to Lipopolysaccharide Mol. Cell. Proteomics, January 1, 2009; 8(1): 201 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. G. Hofman, M. O. Ruonala, A. N. Bader, D. van den Heuvel, J. Voortman, R. C. Roovers, A. J. Verkleij, H. C. Gerritsen, and P. M. P. van Bergen en Henegouwen EGF induces coalescence of different lipid rafts J. Cell Sci., August 1, 2008; 121(15): 2519 - 2528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Chinni, H. Yamamoto, Z. Dong, A. Sabbota, R. D. Bonfil, and M. L. Cher CXCL12/CXCR4 Transactivates HER2 in Lipid Rafts of Prostate Cancer Cells and Promotes Growth of Metastatic Deposits in Bone Mol. Cancer Res., March 1, 2008; 6(3): 446 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pertusa, C. Morenilla-Palao, C. Carteron, F. Viana, and H. Cabedo Transcriptional Control of Cholesterol Biosynthesis in Schwann Cells by Axonal Neuregulin 1 J. Biol. Chem., September 28, 2007; 282(39): 28768 - 28778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Raghu, N. Sharma-Walia, M. V. Veettil, S. Sadagopan, A. Caballero, R. Sivakumar, L. Varga, V. Bottero, and B. Chandran Lipid Rafts of Primary Endothelial Cells Are Essential for Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8-Induced Phosphatidylinositol 3-Kinase and RhoA-GTPases Critical for Microtubule Dynamics and Nuclear Delivery of Viral DNA but Dispensable for Binding and Entry J. Virol., August 1, 2007; 81(15): 7941 - 7959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Adachi, T. Nagao, H. I. Ingolfsson, F. R. Maxfield, O. S. Andersen, L. Kopelovich, and I. B. Weinstein The Inhibitory Effect of (-)-Epigallocatechin Gallate on Activation of the Epidermal Growth Factor Receptor Is Associated with Altered Lipid Order in HT29 Colon Cancer Cells Cancer Res., July 1, 2007; 67(13): 6493 - 6501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fujita, J. Cheng, M. Hirakawa, K. Furukawa, S. Kusunoki, and T. Fujimoto Gangliosides GM1 and GM3 in the Living Cell Membrane Form Clusters Susceptible to Cholesterol Depletion and Chilling Mol. Biol. Cell, June 1, 2007; 18(6): 2112 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Schley, D. N. Brindley, and C. J. Field (n-3) PUFA Alter Raft Lipid Composition and Decrease Epidermal Growth Factor Receptor Levels in Lipid Rafts of Human Breast Cancer Cells J. Nutr., March 1, 2007; 137(3): 548 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Khare, C. Holgren, and A. M. Samarel Deoxycholic acid differentially regulates focal adhesion kinase phosphorylation: role of tyrosine phosphatase ShP2 Am J Physiol Gastrointest Liver Physiol, December 1, 2006; 291(6): G1100 - G1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jean-Louis, S. Akare, M. A. Ali, E. A. Mash Jr., E. Meuillet, and J. D. Martinez Deoxycholic Acid Induces Intracellular Signaling through Membrane Perturbations J. Biol. Chem., May 26, 2006; 281(21): 14948 - 14960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Mazie, J. K. Spix, E. R. Block, H. B. Achebe, and J. K. Klarlund Epithelial cell motility is triggered by activation of the EGF receptor through phosphatidic acid signaling J. Cell Sci., April 15, 2006; 119(8): 1645 - 1654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Li, M. J. Park, S.-K. Ye, C.-W. Kim, and Y.-N. Kim Elevated Levels of Cholesterol-Rich Lipid Rafts in Cancer Cells Are Correlated with Apoptosis Sensitivity Induced by Cholesterol-Depleting Agents Am. J. Pathol., April 1, 2006; 168(4): 1107 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-X. Zhu, S. Goldoni, G. Bix, R. T. Owens, D. J. McQuillan, C. C. Reed, and R. V. Iozzo Decorin Evokes Protracted Internalization and Degradation of the Epidermal Growth Factor Receptor via Caveolar Endocytosis J. Biol. Chem., September 16, 2005; 280(37): 32468 - 32479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Dittmann, C. Mayer, B. Fehrenbacher, M. Schaller, U. Raju, L. Milas, D. J. Chen, R. Kehlbach, and H. P. Rodemann Radiation-induced Epidermal Growth Factor Receptor Nuclear Import Is Linked to Activation of DNA-dependent Protein Kinase J. Biol. Chem., September 2, 2005; 280(35): 31182 - 31189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. McLaughlin, S. O. Smith, M. J. Hayman, and D. Murray An Electrostatic Engine Model for Autoinhibition and Activation of the Epidermal Growth Factor Receptor (EGFR/ErbB) Family J. Gen. Physiol., June 27, 2005; 126(1): 41 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Lin and D. J. Takemoto Oxidative Activation of Protein Kinase C{gamma} through the C1 Domain: EFFECTS ON GAP JUNCTIONS J. Biol. Chem., April 8, 2005; 280(14): 13682 - 13693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Fessler, S. K. Young, S. Jeyaseelan, J. G. Lieber, P. G. Arndt, J. A. Nick, and G. S. Worthen A Role for Hydroxy-Methylglutaryl Coenzyme A Reductase in Pulmonary Inflammation and Host Defense Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 606 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Fessler, P. G. Arndt, S. C. Frasch, J. G. Lieber, C. A. Johnson, R. C. Murphy, J. A. Nick, D. L. Bratton, K. C. Malcolm, and G. S. Worthen Lipid Rafts Regulate Lipopolysaccharide-induced Activation of Cdc42 and Inflammatory Functions of the Human Neutrophil J. Biol. Chem., September 17, 2004; 279(38): 39989 - 39998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Seveau, H. Bierne, S. Giroux, M.-C. Prevost, and P. Cossart Role of lipid rafts in E-cadherin- and HGF-R/Met-mediated entry of Listeria monocytogenes into host cells J. Cell Biol., August 30, 2004; 166(5): 743 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Danthi and M. Chow Cholesterol Removal by Methyl-{beta}-Cyclodextrin Inhibits Poliovirus Entry J. Virol., January 1, 2004; 78(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Westover, D. F. Covey, H. L. Brockman, R. E. Brown, and L. J. Pike Cholesterol Depletion Results in Site-specific Increases in Epidermal Growth Factor Receptor Phosphorylation due to Membrane Level Effects: STUDIES WITH CHOLESTEROL ENANTIOMERS J. Biol. Chem., December 19, 2003; 278(51): 51125 - 51133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Odintsova, J. Voortman, E. Gilbert, and F. Berditchevski Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR J. Cell Sci., November 15, 2003; 116(22): 4557 - 4566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Pike Lipid rafts: bringing order to chaos J. Lipid Res., April 1, 2003; 44(4): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |