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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 Martelli, M. P. Articles by Bierer, B. E. Search for Related Content PubMed PubMed Citation Articles by Martelli, M. P. Articles by Bierer, B. E. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 September 2000, Vol. 96, No. 6, pp. 2181-2190 IMMUNOBIOLOGY Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation Maria Paola Martelli, Huamao Lin, Weiguo Zhang, Lawrence E. Samelson, and Barbara E. Bierer From the Laboratory of Lymphocyte Biology, National Heart, Lung, and Blood Institute, Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD. Activation of T cells can be initiated through cell surface molecules in addition to the T-cell receptor-CD3 (TCR-CD3) complex. In human T cells, ligation of the CD2 molecule by mitogenic pairs of anti-CD2 monoclonal antibodies activates T cells via biochemical signaling pathways similar but not identical to those elicited on TCR engagement. This study describes a key role for the p36/38 membrane adapter protein linker for T cell activation (LAT) in CD2-mediated T-cell activation. Following ligation of CD2 on the surface of the Jurkat T-cell line and human purified T cells, LAT was tyrosine phosphorylated and shown to associate in vivo with a number of other tyrosine phosphorylated proteins including PLC-1, Grb-2, and SLP-76. Using Jurkat cell lines deficient in ZAP70/Syk (P116) or LAT (ANJ3) expression, CD2-dependent PLC-1 and SLP-76 tyrosine phosphorylation required expression both of ZAP70 or Syk and of LAT. As predicted, the absence of either LAT or ZAP70/Syk kinases correlated with a defect in the induction of nuclear factor of activated T cells (NFAT) transcriptional activity, activation of the interleukin-2 promoter, and ERK phosphorylation following CD2 stimulation. These data suggest that LAT is an adapter protein important for the regulation of CD2-mediated T-cell activation. © 2000 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: R. Rodriguez-Manzanet, J. H. Meyers, S. Balasubramanian, J. Slavik, N. Kassam, V. Dardalhon, E. A. Greenfield, A. C. Anderson, R. A. Sobel, D. A. Hafler, et al. TIM-4 Expressed on APCs Induces T Cell Expansion and Survival J. Immunol., April 1, 2008; 180(7): 4706 - 4713. [Abstract] [Full Text] [PDF] R. Seggewiss, K. Lore, E. Greiner, M. K. Magnusson, D. A. Price, D. C. Douek, C. E. Dunbar, and A. Wiestner Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner Blood, March 15, 2005; 105(6): 2473 - 2479. [Abstract] [Full Text] [PDF] A. Wiestner, A. Rosenwald, T. S. Barry, G. Wright, R. E. Davis, S. E. Henrickson, H. Zhao, R. E. Ibbotson, J. A. Orchard, Z. Davis, et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile Blood, June 15, 2003; 101(12): 4944 - 4951. [Abstract] [Full Text] [PDF] E. Teixeiro, P. Fuentes, B. Galocha, B. Alarcon, and R. Bragado T Cell Receptor-mediated Signal Transduction Controlled by the beta Chain Transmembrane Domain. APOPTOSIS-DEFICIENT CELLS DISPLAY UNBALANCED MITOGEN-ACTIVATED PROTEIN KINASES ACTIVITIES UPON T CELL RECEPTOR ENGAGEMENT J. Biol. Chem., February 1, 2002; 277(6): 3993 - 4002. [Abstract] [Full Text] [PDF] Y. Zaffran, O. Destaing, A. Roux, S. Ory, T. Nheu, P. Jurdic, C. Rabourdin-Combe, and A. L. Astier CD46/CD3 Costimulation Induces Morphological Changes of Human T Cells and Activation of Vav, Rac, and Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase J. Immunol., December 15, 2001; 167(12): 6780 - 6785. [Abstract] [Full Text] [PDF] M. P. Martelli, J. Boomer, M. Bu, and B. E. Bierer T Cell Regulation of p62dok (Dok1) Association with Crk-L J. Biol. Chem., November 30, 2001; 276(49): 45654 - 45661. [Abstract] [Full Text] [PDF] B. S. Wilson, J. R. Pfeiffer, Z. Surviladze, E. A. Gaudet, and J. M. Oliver High resolution mapping of mast cell membranes reveals primary and secondary domains of Fc{epsilon}RI and LAT J. Cell Biol., August 6, 2001; 154(3): 645 - 658. [Abstract] [Full Text] [PDF]

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