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Titolo:
Enhancement of epidermal growth factor signaling and activation of src kinase by gangliosides
Autore:
Li, RX; Liu, YH; Ladisch, S;
Indirizzi:
Childrens Res Inst, Ctr Canc & Transplantat Biol, Glycobiol Program, Washington, DC 20010 USA Childrens Res Inst Washington DC USA 20010 gram, Washington, DC 20010 USA George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA George Washington Univ Washington DC USA 20052 , Washington, DC 20052 USA George Washington Univ, Sch Med, Dept Biochem Mol Biol, Washington, DC 20052 USA George Washington Univ Washington DC USA 20052 , Washington, DC 20052 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 46, volume: 276, anno: 2001,
pagine: 42782 - 42792
SICI:
0021-9258(20011116)276:46<42782:EOEGFS>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
T-CELL ACTIVATION; LIPID RAFTS; FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; MEDIATED MODULATION; CAVEOLAE MEMBRANE; DOMAIN; TRANSDUCTION; MICRODOMAINS; PATHWAY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Li, RX Childrens Res Inst, Ctr Canc & Transplantat Biol, Glycobiol Program, 111 Michigan Ave NW, Washington, DC 20010 USA Childrens Res Inst 111 Michigan Ave NW Washington DC USA 20010 USA
Citazione:
R.X. Li et al., "Enhancement of epidermal growth factor signaling and activation of src kinase by gangliosides", J BIOL CHEM, 276(46), 2001, pp. 42782-42792

Abstract

In a recent study, inhibition of cellular ganglioside synthesis blocked growth factor-induced fibroblast proliferation. Conversely, enrichment of cell membrane gangliosides by ganglioside preincubation enhanced growth factor-elicited cell proliferation. In the absence of serum and growth factors, NeuNAc alpha2-3Gal beta1-3GalNAc beta1-4(NeuNAc alpha2-3)Gal beta1-4Glc beta1-1Cer (G(D1a)) acted like a growth factor when cells were pretreated with the ganglioside, stimulating proliferation of normal human dermal fibroblasts and Swiss 3T3 fibroblasts. In contrast, growth inhibition was observed when high concentrations of gangliosides were continuously present in the culture medium during incubation of fibroblasts with growth factors (Li, R., Manela, J., Kong, Y., and Ladisch, S. (2000) J. Biol. Chem. 275,34213-34223). Here, we investigated the mechanisms whereby gangliosides elicit proliferation-coupled signaling in normal human dermal fibroblasts. Incubation of the fibroblasts with G(D1a) enhanced epidermal growth factor (EGF) receptorautophosphorylation and Ras and MAPK activation in a dose-dependent manner. Exposure of the cells to G(D1a) also enhanced the phosphorylation of Elk-1 by the activated MAPK. Brief pretreatment of the cells with PD98059 blocked the enhancing effect of gangliosides on EGF-induced MAPK activation. In the absence of serum and growth factors, G(D1a) incubation induced phosphorylation of Src kinase, Ras activation, and phosphorylation of MAPK and Elk-1 in a dose-dependent manner. The activation of Src kinase was confirmed byenhanced Src kinase activity. Brief treatment of the cells with PPI blocked the activation of Src kinase and MAPK. Again, PD98059 treatment inhibitedganglioside-elicited MAPK phosphorylation. Among the gangliosides tested, G(D1a), was the most active molecule, whereas lactosylceramide was the least active one, indicating relative structural specificity of the gangliosideaction. In conclusion, gangliosides promote fibroblast proliferation through enhancement of growth factor signaling and activation of Src kinase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:44:39