Ganglioside modulates ligand binding to the epidermal growth factor receptor

X. Wang, Z. Rahman, P. Sun, Emmanuelle Meuillet, D. George, E. G. Bremer, A. Al-Qamari, A. S. Paller

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Whereas previous investigations have shown that pharmacologic addition of gangliosides inhibits keratinocyte proliferation by downregulating epidermal growth factor receptor phosphorylation, the underlying biochemical basis and physiologic relevance are unknown. Using Scatchard and displacement plots, we have shown that supplemental purified gangliosides decrease the binding of 125I-labeled epidermal growth factor to keratinocyte-derived SCC12 cells. Conversely, SCC12 cells transfected with sialidase and thus depleted of gangliosides show increased ligand binding to the epidermal growth factor receptor, which is consistent with their increased proliferation in response to epidermal growth factor and transforming growth factor-α, and increased phosphorylation of the epidermal growth factor receptor, and downstream signal transduction pathway components. The mechanism of the altered binding appears to involve primarily decreased numbers of available receptors within the intact membrane, but not altered receptor protein expression. These studies provide evidence that the effect of gangliosides on keratinocyte proliferation results, at least in part, from the direct binding of ganglioside to the receptor and disruption of the receptor - ligand interaction. Manipulation of membrane ganglioside content may be a powerful new means to alter epidermal growth factor receptor-dependent cell proliferation.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalJournal of Investigative Dermatology
Volume116
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Gangliosides
Epidermal Growth Factor Receptor
Ligands
Keratinocytes
Phosphorylation
Epidermal Growth Factor
Membranes
Neuraminidase
Transforming Growth Factors
Signal transduction
Cell proliferation
Signal Transduction
Down-Regulation
Cell Proliferation
Proteins

Keywords

  • Epidermis
  • Glycosphingolipid
  • Glycosylation
  • Sialidase

ASJC Scopus subject areas

  • Dermatology

Cite this

Ganglioside modulates ligand binding to the epidermal growth factor receptor. / Wang, X.; Rahman, Z.; Sun, P.; Meuillet, Emmanuelle; George, D.; Bremer, E. G.; Al-Qamari, A.; Paller, A. S.

In: Journal of Investigative Dermatology, Vol. 116, No. 1, 2001, p. 69-76.

Research output: Contribution to journalArticle

Wang, X, Rahman, Z, Sun, P, Meuillet, E, George, D, Bremer, EG, Al-Qamari, A & Paller, AS 2001, 'Ganglioside modulates ligand binding to the epidermal growth factor receptor', Journal of Investigative Dermatology, vol. 116, no. 1, pp. 69-76. https://doi.org/10.1046/j.1523-1747.2001.00222.x
Wang, X. ; Rahman, Z. ; Sun, P. ; Meuillet, Emmanuelle ; George, D. ; Bremer, E. G. ; Al-Qamari, A. ; Paller, A. S. / Ganglioside modulates ligand binding to the epidermal growth factor receptor. In: Journal of Investigative Dermatology. 2001 ; Vol. 116, No. 1. pp. 69-76.
@article{7ac31cc6070349a89116a66bc75d4127,
title = "Ganglioside modulates ligand binding to the epidermal growth factor receptor",
abstract = "Whereas previous investigations have shown that pharmacologic addition of gangliosides inhibits keratinocyte proliferation by downregulating epidermal growth factor receptor phosphorylation, the underlying biochemical basis and physiologic relevance are unknown. Using Scatchard and displacement plots, we have shown that supplemental purified gangliosides decrease the binding of 125I-labeled epidermal growth factor to keratinocyte-derived SCC12 cells. Conversely, SCC12 cells transfected with sialidase and thus depleted of gangliosides show increased ligand binding to the epidermal growth factor receptor, which is consistent with their increased proliferation in response to epidermal growth factor and transforming growth factor-α, and increased phosphorylation of the epidermal growth factor receptor, and downstream signal transduction pathway components. The mechanism of the altered binding appears to involve primarily decreased numbers of available receptors within the intact membrane, but not altered receptor protein expression. These studies provide evidence that the effect of gangliosides on keratinocyte proliferation results, at least in part, from the direct binding of ganglioside to the receptor and disruption of the receptor - ligand interaction. Manipulation of membrane ganglioside content may be a powerful new means to alter epidermal growth factor receptor-dependent cell proliferation.",
keywords = "Epidermis, Glycosphingolipid, Glycosylation, Sialidase",
author = "X. Wang and Z. Rahman and P. Sun and Emmanuelle Meuillet and D. George and Bremer, {E. G.} and A. Al-Qamari and Paller, {A. S.}",
year = "2001",
doi = "10.1046/j.1523-1747.2001.00222.x",
language = "English (US)",
volume = "116",
pages = "69--76",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Ganglioside modulates ligand binding to the epidermal growth factor receptor

AU - Wang, X.

AU - Rahman, Z.

AU - Sun, P.

AU - Meuillet, Emmanuelle

AU - George, D.

AU - Bremer, E. G.

AU - Al-Qamari, A.

AU - Paller, A. S.

PY - 2001

Y1 - 2001

N2 - Whereas previous investigations have shown that pharmacologic addition of gangliosides inhibits keratinocyte proliferation by downregulating epidermal growth factor receptor phosphorylation, the underlying biochemical basis and physiologic relevance are unknown. Using Scatchard and displacement plots, we have shown that supplemental purified gangliosides decrease the binding of 125I-labeled epidermal growth factor to keratinocyte-derived SCC12 cells. Conversely, SCC12 cells transfected with sialidase and thus depleted of gangliosides show increased ligand binding to the epidermal growth factor receptor, which is consistent with their increased proliferation in response to epidermal growth factor and transforming growth factor-α, and increased phosphorylation of the epidermal growth factor receptor, and downstream signal transduction pathway components. The mechanism of the altered binding appears to involve primarily decreased numbers of available receptors within the intact membrane, but not altered receptor protein expression. These studies provide evidence that the effect of gangliosides on keratinocyte proliferation results, at least in part, from the direct binding of ganglioside to the receptor and disruption of the receptor - ligand interaction. Manipulation of membrane ganglioside content may be a powerful new means to alter epidermal growth factor receptor-dependent cell proliferation.

AB - Whereas previous investigations have shown that pharmacologic addition of gangliosides inhibits keratinocyte proliferation by downregulating epidermal growth factor receptor phosphorylation, the underlying biochemical basis and physiologic relevance are unknown. Using Scatchard and displacement plots, we have shown that supplemental purified gangliosides decrease the binding of 125I-labeled epidermal growth factor to keratinocyte-derived SCC12 cells. Conversely, SCC12 cells transfected with sialidase and thus depleted of gangliosides show increased ligand binding to the epidermal growth factor receptor, which is consistent with their increased proliferation in response to epidermal growth factor and transforming growth factor-α, and increased phosphorylation of the epidermal growth factor receptor, and downstream signal transduction pathway components. The mechanism of the altered binding appears to involve primarily decreased numbers of available receptors within the intact membrane, but not altered receptor protein expression. These studies provide evidence that the effect of gangliosides on keratinocyte proliferation results, at least in part, from the direct binding of ganglioside to the receptor and disruption of the receptor - ligand interaction. Manipulation of membrane ganglioside content may be a powerful new means to alter epidermal growth factor receptor-dependent cell proliferation.

KW - Epidermis

KW - Glycosphingolipid

KW - Glycosylation

KW - Sialidase

UR - http://www.scopus.com/inward/record.url?scp=0035136450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035136450&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1747.2001.00222.x

DO - 10.1046/j.1523-1747.2001.00222.x

M3 - Article

C2 - 11168800

AN - SCOPUS:0035136450

VL - 116

SP - 69

EP - 76

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 1

ER -