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* Group of Cell Activation and Gene Expression, Instituto de Biologia Molecular e Celular, and
Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal; and
Institut National de la Santé et de la Recherche Médicale, Unité 567, Institut Cochin, Département de Biologie Cellulaire, Laboratoire labellisé par la Ligue Nationale contre le Cancer, Université René Descartes, Paris, France
In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions. In murine T cells, a significant fraction of CD2 associates with membrane lipid rafts. We have addressed the mechanisms that control the localization of rat CD2 at the plasma membrane, and its redistribution within lipid rafts induced upon activation. Following incubation of rat CD2-expressing cells with radioactive-labeled palmitic acid, or using CD2 mutants with Cys226 and Cys228 replaced by alanine residues, we found no evidence that rat CD2 was subjected to lipid modifications that could favor the translocation to lipid rafts, discarding palmitoylation as the principal mechanism for raft addressing. In contrast, using Jurkat cells expressing different CD2 and Lck mutants, we show that the association of CD2 with the rafts fully correlates with CD2 capacity to bind to Lck. As CD2 physically interacts with both Lck and Fyn, preferentially inside lipid rafts, and reflecting the increase of CD2 in lipid rafts following activation, CD2 can mediate the interaction between the two kinases and the consequent boost in kinase activity in lipid rafts.
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1 This work was funded by European Regional Development Fund FEDER, by Programa Operacional Ciência, Tecnologia, Inovação (POCTI) and Programa Operacional Ciência e Inovação 2010 from the Fundação para a Ciência e a Tecnologia (FCT), and support from the Programa Pessoa (cooperation Grices/Egide). R.J.N. and M.B. are recipients of studentships from FCT-POCTI. M.A.A.C. is supported by a Postdoctoral Fellowship from FCT-Programa Operacional Sociedade da Informação.
2 Current address: Lymphocyte Development Group, Medical Research Council, Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, U.K.
3 Address correspondence and reprint requests to Dr. Alexandre M. Carmo, Group of Cell Activation and Gene Expression, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal. E-mail address: acarmo{at}ibmc.up.pt
4 Abbreviations used in this paper: SH3, Src homology 3; PAG, phosphoprotein associated with glycosphingolipid-enriched microdomains; LAT, linker for activation of T cell.
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