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PMID:10330413

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Citation

Sheets, ED, Holowka, D and Baird, B (1999) Critical role for cholesterol in Lyn-mediated tyrosine phosphorylation of FcepsilonRI and their association with detergent-resistant membranes. J. Cell Biol. 145:877-87

Abstract

Tyrosine phosphorylation of the high affinity immunoglobulin (Ig)E receptor (FcepsilonRI) by the Src family kinase Lyn is the first known biochemical step that occurs during activation of mast cells and basophils after cross-linking of FcepsilonRI by antigen. The hypothesis that specialized regions in the plasma membrane, enriched in sphingolipids and cholesterol, facilitate the coupling of Lyn and FcepsilonRI was tested by investigating functional and structural effects of cholesterol depletion on Lyn/FcepsilonRI interactions. We find that cholesterol depletion with methyl-beta-cyclodextrin substantially reduces stimulated tyrosine phosphorylation of FcepsilonRI and other proteins while enhancing more downstream events that lead to stimulated exocytosis. In parallel to its inhibition of tyrosine phosphorylation, cholesterol depletion disrupts the interactions of aggregated FcepsilonRI and Lyn on intact cells and also disrupts those interactions with detergent-resistant membranes that are isolated by sucrose gradient ultracentrifugation of lysed cells. Importantly, cholesterol repletion restores receptor phosphorylation together with the structural interactions. These results provide strong evidence that membrane structure, maintained by cholesterol, plays a critical role in the initiation of FcepsilonRI signaling.

Links

PubMed PMC2133197

Keywords

Cell Line; Cell Membrane/drug effects; Cell Membrane/metabolism; Cholesterol/physiology; Cross-Linking Reagents; Cyclodextrins/pharmacology; Detergents; Humans; Octoxynol; Phosphorylation; Receptors, IgE/metabolism; Tyrosine/metabolism; beta-Cyclodextrins; src-Family Kinases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:LYN

involved_in

GO:0006991: response to sterol depletion

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:LYN

involved_in

GO:0009743: response to carbohydrate

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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