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Role of gangliosides in the association of ErbB2 with lipid rafts in mammary epithelial HC11 cells
Author(s) -
Sottocornola Elena,
Misasi Roberta,
Mattei Vincenzo,
Ciarlo Laura,
Gradini Roberto,
Garofalo Tina,
Berra Bruno,
Colombo Irma,
Sorice Maurizio
Publication year - 2006
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2006.05203.x
Subject(s) - lipid raft , ganglioside , signal transduction , microbiology and biotechnology , colocalization , tyrosine kinase , chemistry , biology , biochemistry
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.

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