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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marmor, M. D. Articles by Julius, M. Search for Related Content PubMed PubMed Citation Articles by Marmor, M. D. Articles by Julius, M. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2001, Vol. 98, No. 5, pp. 1489-1497 IMMUNOBIOLOGY Role for lipid rafts in regulating interleukin-2 receptor signaling Mina D. Marmor and Michael Julius From Sunnybrook and Women's College Health Sciences Centre and the Department of Immunology, University of Toronto, Ontario, Canada. Lipid rafts are plasma membrane microdomains characterized by a unique lipid environment enriched in gangliosides and cholesterol, leading to their insolubility in nonionic detergents. Many receptors are constitutively or inducibly localized in lipid rafts, which have been shown to function as platforms coordinating the induction of signaling pathways. In this report, the first evidence is provided for a role of these lipid microdomains in regulating interleukin-2 receptor (IL-2R) signaling. It is demonstrated that antibody- or ligand-mediated immobilization of components of lipid rafts, glycosyl-phosphatidyl-inositol-anchored proteins, and the GM1 ganglioside, respectively, inhibit IL-2-induced proliferation in T cells. IL-2R is shown to be constitutively enriched in rafts and further enriched in the presence of immobilized anti-Thy-1. In contrast, IL-2R and IL-2R, as well as JAK1 and JAK3, are found in soluble membrane fractions, and their localization is not altered by anti-Thy-1. IL-2-mediated heterotrimerization of IL-2R chains is shown to occur within soluble membrane fractions, exclusively, as is the activation of JAK1 and JAK3. As predicted by these results, the disruption of lipid raft integrity did not impair IL-2-induced signaling. Thus, the sequestration of IL-2R within lipid microdomains restricts its intermolecular interactions and regulates IL-2R signaling through impeding its association with IL-2R and IL-2R. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Jahn, S. Sindhu, S. Gooch, P. Seipel, P. Lavori, E. Leifheit, and K. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020