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Cutting Edge |
,¶
* Department of Oncogenesis, Graduate School of Medicine,
Faculty of Medicine, School of Allied Health Sciences,
Department of Oncogene Research, Research Institute for Microbial Diseases,
Division of Molecular Genetics, Institute for Molecular and Cellular Biology, Osaka University, Osaka, Japan; and
¶ Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama, Japan
In resting T cells, Csk is constitutively localized in lipid rafts by virtue of interaction with a phosphorylated adaptor protein, Csk-binding protein (Cbp)/phosphoprotein associated with glycolipid-enriched microdomains, and sets an activation threshold in TCR signaling. In this study, we examined a kinase responsible for Cbp phosphorylation in T cell membrane rafts. By analyzing T cells from Fyn-/- mice, we clearly demonstrated that Fyn, but not Lck, has its kinase activity in membrane rafts, and plays a critical role in Cbp phosphorylation, Cbp-Csk interaction, and Csk kinase activity. Naive CD44lowCD62 ligandhigh T cells were substantially reduced in Fyn-/- mice, presumably due to the inhibition of Cbp phosphorylation. Thus, Fyn mediates Cbp-Csk interaction and recruits Csk to rafts by phosphorylating Cbp. Csk recruited to rafts would then be activated and inhibit the kinase activity of Lck to keep resting T cells in a quiescent state. Our results elucidate a negative regulatory role for Fyn in proximal TCR signaling in lipid rafts.
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