Plasma membrane domain organization regulates EGFR signaling in tumor cells.

Plasma membrane domain organization regulates EGFR signaling in tumor cells. Research Abstract Details 

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Plasma membrane domain organization regulates EGFR signaling in tumor cells. Abstract Text:

Patrick Lajoie,Emily A Partridge,Ginette Guay,Jacky G Goetz,Judy Pawling,Annick Lagana,Bharat Joshi,James W Dennis,Ivan R Nabi,Patrick Lajoie,Emily A Partridge,Ginette Guay,Jacky G Goetz,Judy Pawling,Annick Lagana,Bharat Joshi,James W Dennis,Ivan R Nabi,

Macromolecular complexes exhibit reduced diffusion in biological membranes; however, the physiological consequences of this characteristic of plasma membrane domain organization remain elusive. We report that competition between the galectin lattice and oligomerized caveolin-1 microdomains for epidermal growth factor (EGF) receptor (EGFR) recruitment regulates EGFR signaling in tumor cells. In mammary tumor cells deficient for Golgi beta1,6N-acetylglucosaminyltransferase V (Mgat5), a reduction in EGFR binding to the galectin lattice allows an increased association with stable caveolin-1 cell surface microdomains that suppresses EGFR signaling. Depletion of caveolin-1 enhances EGFR diffusion, responsiveness to EGF, and relieves Mgat5 deficiency-imposed restrictions on tumor cell growth. In Mgat5(+/+) tumor cells, EGFR association with the galectin lattice reduces first-order EGFR diffusion rates and promotes receptor interaction with the actin cytoskeleton. Importantly, EGFR association with the lattice opposes sequestration by caveolin-1, overriding its negative regulation of EGFR diffusion and signaling. Therefore, caveolin-1 is a conditional tumor suppressor whose loss is advantageous when beta1,6GlcNAc-branched N-glycans are below a threshold for optimal galectin lattice formation.

Plasma membrane domain organization regulates EGFR signaling in tumor cells. Publishing Authors By Initials

P Lajoie,EA Partridge,G Guay,JG Goetz,J Pawling,A Lagana,B Joshi,JW Dennis,IR Nabi,P Lajoie,EA Partridge,G Guay,JG Goetz,J Pawling,A Lagana,B Joshi,JW Dennis,IR Nabi,

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Plasma membrane domain organization regulates EGFR signaling in tumor cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of cell biology

VOLUME: 179

Page Numbers: 341-56

Journal Abbreviation: J. Cell Biol.

ISSN: 0021-9525

DAY: 15

MONTH: 10

YEAR: 2007

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LANGUAGE: eng

NlmUniqueID: 375356

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AFFILIATION: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.

Country: United States

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MEDLINETA: J Cell Biol

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