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*
Department of Oncology, Biomedical Research Center, Osaka University Medical School, Osaka, Japan;
Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan; and
Saga Medical College, Saga, Japan
While CD28 functions as the major T cell costimulatory receptor, a number of other T cell molecules have also been described to induce T cell costimulation. Here, we investigated the mechanisms by which costimulatory molecules other than CD28 contribute to T cell activation. Non-CD28 costimulatory molecules such as CD5, CD9, CD2, and CD44 were present in the detergent-insoluble glycolipid-enriched (DIG) fraction/raft of the T cell surface, which is rich in TCR signaling molecules and generates a TCR signal upon recruitment of the TCR complex. Compared with CD3 ligation, coligation of CD3 and CD5 as an example of DIG-resident costimulatory molecules led to an enhanced association of CD3 and DIG. Such a DIG redistribution markedly up-regulated TCR signaling as observed by ZAP-70/LAT activation and Ca2+ influx. Disruption of DIG structure using an agent capable of altering cholesterol organization potently diminished Ca2+ mobilization induced by the coligation of CD3 and CD5. This was associated with the inhibition of the redistribution of DIG although the association of CD3 and CD5 was not affected. Thus, the DIG-resident costimulatory molecules exert their costimulatory effects by contributing to an enhanced association of TCR/CD3 and DIG.
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H. Lin, M. P. Martelli, and B. E. Bierer The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation Int. Immunol., January 1, 2001; 13(1): 13 - 22. [Abstract] [Full Text] [PDF]
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J. M. Vila, J. Calvo, L. Places, O. Padilla, M. Arman, I. Gimferrer, C. Aussel, J. Vives, and F. Lozano Role of Two Conserved Cytoplasmic Threonine Residues (T410 and T412) in CD5 Signaling J. Immunol., January 1, 2001; 166(1): 396 - 402. [Abstract] [Full Text] [PDF]
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P. J. R. Ebert, J. F. Baker, and J. A. Punt Immature CD4+CD8+ Thymocytes Do Not Polarize Lipid Rafts in Response to TCR-Mediated Signals J. Immunol., November 15, 2000; 165(10): 5435 - 5442. [Abstract] [Full Text] [PDF]
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F. Michel, G. Mangino, G. Attal-Bonnefoy, L. Tuosto, A. Alcover, A. Roumier, D. Olive, and O. Acuto CD28 Utilizes Vav-1 to Enhance TCR-Proximal Signaling and NF-AT Activation J. Immunol., October 1, 2000; 165(7): 3820 - 3829. [Abstract] [Full Text] [PDF]
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M. P. Martelli, H. Lin, W. Zhang, L. E. Samelson, and B. E. Bierer Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation Blood, September 15, 2000; 96(6): 2181 - 2190. [Abstract] [Full Text] [PDF]
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C. Claas, C. S. Stipp, and M. E. Hemler Evaluation of Prototype Transmembrane 4 Superfamily Protein Complexes and Their Relation to Lipid Rafts J. Biol. Chem., March 9, 2001; 276(11): 7974 - 7984. [Abstract] [Full Text] [PDF]
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R. A. Rebres, J. M. Green, M. I. Reinhold, M. Ticchioni, and E. J. Brown Membrane Raft Association of CD47 Is Necessary for Actin Polymerization and Protein Kinase C theta Translocation in Its Synergistic Activation of T Cells J. Biol. Chem., March 2, 2001; 276(10): 7672 - 7680. [Abstract] [Full Text] [PDF]
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H. Yang and E. L. Reinherz Dynamic Recruitment of Human CD2 into Lipid Rafts. LINKAGE TO T CELL SIGNAL TRANSDUCTION J. Biol. Chem., May 25, 2001; 276(22): 18775 - 18785. [Abstract] [Full Text] [PDF]
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C. S. Stipp, D. Orlicky, and M. E. Hemler FPRP, a Major, Highly Stoichiometric, Highly Specific CD81- and CD9-associated Protein J. Biol. Chem., February 9, 2001; 276(7): 4853 - 4862. [Abstract] [Full Text] [PDF]
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X. A. Zhang, A. L. Bontrager, and M. E. Hemler Transmembrane-4 Superfamily Proteins Associate with Activated Protein Kinase C (PKC) and Link PKC to Specific beta 1 Integrins J. Biol. Chem., June 29, 2001; 276(27): 25005 - 25013. [Abstract] [Full Text] [PDF]
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M. Zubiaur, O. Fernandez, E. Ferrero, J. Salmeron, B. Malissen, F. Malavasi, and J. Sancho CD38 Is Associated with Lipid Rafts and upon Receptor Stimulation Leads to Akt/Protein Kinase B and Erk Activation in the Absence of the CD3-zeta Immune Receptor Tyrosine-based Activation Motifs J. Biol. Chem., January 4, 2002; 277(1): 13 - 22. [Abstract] [Full Text] [PDF]
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B. S. Hostager, I. M. Catlett, and G. A. Bishop Recruitment of CD40 and Tumor Necrosis Factor Receptor-associated Factors 2 and 3 to Membrane Microdomains during CD40 Signaling J. Biol. Chem., May 12, 2000; 275(20): 15392 - 15398. [Abstract] [Full Text] [PDF]
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T. Ishii, K. Ohnuma, A. Murakami, N. Takasawa, S. Kobayashi, N. H. Dang, S. F. Schlossman, and C. Morimoto CD26-mediated signaling for T cell activation occurs in lipid rafts through its association with CD45RO PNAS, October 9, 2001; 98(21): 12138 - 12143. [Abstract] [Full Text] [PDF]
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 M. E. Hemler Specific tetraspanin functions J. Cell Biol., December 24, 2001; 155(7): 1103 - 1108. [Abstract] [Full Text] [PDF]
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 H. Yuan, E. Takeuchi, and D. J. Salant Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton Am J Physiol Renal Physiol, April 1, 2002; 282(4): F585 - F591. [Abstract] [Full Text] [PDF]
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