Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals

Teruhiko Mitsuda, Keiko Furukawa, Satoshi Fukumoto, Hiroshi Miyazaki, Takeshi Urano, Koichi Furukawa

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

To investigate the molecular mechanisms of gangliosides for the regulation of cell proliferation, Swiss 3T3 cells were transfected with GM2/GD2 synthase and GM1 synthase cDNAs, resulting in the establishment of GM1-expressing (GM1+) lines. Compared with the vector control (GM1-) cell lines, GM1+ cells exhibited reduced cell proliferation by stimulation with platelet-derived growth factor (PDGF). In accordance with the reduced cell growth, GM1+ cells showed earlier decreases in the phosphorylation levels of PDGF receptor and less activation of MAP kinases than GM1- cells. To analyze the effects of GM1 expression on the PDGF/PDGF receptor (PDGFR) signals, the glycolipid-enriched microdomain (GEM) was isolated and the following results were obtained. (i) PDGFR predominantly distributed in the non-GEM fraction in GM1+ cells, while it was present in both GEM and non-GEM fractions in GM1- cells. (ii) Activation of PDGFR as detected by anti-phosphotyrosine antibody occurred almost in parallel with existing amounts of PDGFR in each fraction. (iii) GM1 binds with PDGFR in GEM fractions. These findings suggested that GM1 regulates signals via PDGF/PDGFR by controlling the distribution of PDGFR in- and outside of GEM, and also interacting with PDGFR in the GEM fraction as a functional constituent of the microdomain.

Original languageEnglish
Pages (from-to)11239-11246
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number13
DOIs
Publication statusPublished - Mar 29 2002

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G(M1) Ganglioside
Platelet-Derived Growth Factor Receptors
Glycolipids
Cell growth
Growth
(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
Platelet-Derived Growth Factor
Cell proliferation
Chemical activation
Cell Proliferation
Swiss 3T3 Cells
Phosphotyrosine
Phosphorylation
Gangliosides
Phosphotransferases
Complementary DNA
Anti-Idiotypic Antibodies
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Overexpression of ganglioside GM1 results in the dispersion of platelet-derived growth factor receptor from glycolipid-enriched microdomains and in the suppression of cell growth signals. / Mitsuda, Teruhiko; Furukawa, Keiko; Fukumoto, Satoshi; Miyazaki, Hiroshi; Urano, Takeshi; Furukawa, Koichi.

In: Journal of Biological Chemistry, Vol. 277, No. 13, 29.03.2002, p. 11239-11246.

Research output: Contribution to journalArticle

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