The clustered Fcγ receptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner
- 1 April 2001
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 31 (4) , 989-998
- https://doi.org/10.1002/1521-4141(200104)31:4<989::aid-immu989>3.0.co;2-v
Abstract
Phosphorylation of clustered Fcγ receptor II (FcγRII) by Src family tyrosine kinases is the earliest event in the receptor signaling cascade. However, the molecular mechanisms for the interaction between FcγRII and these kinases are not elucidated. To asses this problem we isolated high molecular weight complexes of cross-linked FcγRII from non-ionic detergent lysates of U937 monocytic cells. CD55, a glycosylphosphatidylinositol-anchored protein, a ganglioside GM1 and Lyn, a Src family tyrosine kinase, were also located in these complexes. Gradient centrifugation demonstrated that the complexes containing cross-linked FcγRII displayed a low buoyant density. The FcγRII present in the complexes underwent tyrosine phosphorylation. Cross-linked FcγRII and Lyn occupied common 100–200 nm detergent-resistant membrane fragments, as demonstrated by immunoprecipitation and microscopy studies. Pretreatment of the cells with β-cyclodextrin, a cholesterol acceptor, depleted membrane cholesterol and released CD55, GM1 and Lyn from the detergent-resistant complexes. In parallel, the association of Lyn with cross-linked FcγRII was disrupted and phosphorylation of the receptor inhibited. Reincorporation of cholesterol evoked the relocation of Lyn into the detergent-resistant membrane fraction and restored both Lyn association with cross-linked FcγRII and tyrosine phosphorylation of the receptor. Our data demonstrate that cholesterol-enriched membrane rafts can facilitate tyrosine phosphorylation of clustered FcγRII by Lyn kinase.Keywords
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