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- Title
Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells.
- Authors
Sottocornola, Elena; Misasi, Roberta; Mattei, Vincenzo; Ciarlo, Laura; Gradini, Roberto; Garofalo, Tina; Berra, Bruno; Colombo, Irma; Sorice, Maurizio
- Abstract
We analyzed the role of gangliosides in the association of the ErbB2 receptor tyrosine-kinase (RTK) with lipid rafts in mammary epithelial HC11 cells. Scanning confocal microscopy experiments revealed a strict ErbB2–GM3 colocalization in wild-type cells. In addition, analysis of membrane fractions obtained using a linear sucrose gradient showed that ErbB2, epidermal growth factor receptor (EGFR) and Shc-p66 (proteins correlated with the ErbB2 signal transduction pathway) were preferentially enriched in lipid rafts together with gangliosides. Blocking of endogenous ganglioside synthesis by (+/–)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol hydrochloride ([D]-PDMP) induced a drastic cell-surface redistribution of ErbB2, EGFR and Shc-p66, within the Triton-soluble fractions, as revealed by linear sucrose-gradient analysis. This redistribution was partially reverted when exogenous GM3 was added to ganglioside-depleted HC11 cells. The results point out the key role of ganglioside GM3 in retaining ErbB2 and signal-transduction-correlated proteins in lipid rafts.
- Subjects
GANGLIOSIDES; PROTEIN-tyrosine kinases; SUCROSE; EPIDERMAL growth factor; CELLULAR signal transduction
- Publication
FEBS Journal, 2006, Vol 273, Issue 8, p1821
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2006.05203.x