| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Chain Signaling Motifs1
,*
Departments of
*
Medicine, and Microbiology and Immunology, and
Howard Hughes Medical Institute, University of California, San Francisco, CA 94143; and
Laboratory of Mammalian Genes and Development, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
The 
ß TCR is a multimeric protein complex comprising
ligand-binding and signal-transducing subunits. The signal transduction
processes are mediated by the immunoreceptor tyrosine-based activation
motifs (ITAMs), and up to 10 ITAMs are present within a single TCR
complex. This multiplicity may allow for signal amplification and/or
the formation of qualitatively distinct intracellular signals. Notably,
the TCR-
subunit contains three ITAMs, and exists as a
disulfide-linked homodimer in the TCR complex. In normal murine
thymocytes and peripheral T cells, a proportion of TCR- molecules is
constitutively tyrosine phosphorylated and associated with the ZAP-70
protein tyrosine kinase. We examined the contribution of the different
TCR- ITAMs in regulating the constitutive phosphorylation of the
TCR- subunit in thymocytes by analyzing TCR--deficient mice that
had been reconstituted with either full-length or single
ITAM-containing TCR- subunits. We report in this work that in the
absence of a full-length TCR- subunit, there is no apparent
constitutive phosphorylation of the remaining TCR/CD3 ITAMs. Following
TCR ligation, all of the CD3 ITAMs become inducibly phosphorylated and
associate with the ZAP-70 protein tyrosine kinase. Regardless of the
number of TCR- ITAMs present in the TCR complex, we report that a
number of molecules involved in downstream signaling events, such as
ZAP-70, SLP-76, and pp36, are all inducibly tyrosine phosphorylated
following TCR ligation. These results support the notion that the
different TCR ITAMs function in a quantitative rather than qualitative
manner.
This article has been cited by other articles:
|
|
 |
|
  J. Mori, A. C. Pearce, J. C. Spalton, B. Grygielska, J. A. Eble, M. G. Tomlinson, Y. A. Senis, and S. P. Watson G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2 J. Biol. Chem., December 19, 2008; 283(51): 35419 - 35427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Andersson, I. Stefanova, G. L. Stephens, and E. M. Shevach CD4+CD25+ regulatory T cells are activated in vivo by recognition of self Int. Immunol., April 1, 2007; 19(4): 557 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Levin and A. Weiss Twisting tails exposed: the evidence for TCR conformational change J. Exp. Med., February 22, 2005; 201(4): 489 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Y. J. Sun, S. T. Kim, I. C. Kim, A. Fahmy, E. L. Reinherz, and G. Wagner Solution structure of the CD3{epsilon}{delta} ectodomain and comparison with CD3{epsilon}{gamma} as a basis for modeling T cell receptor topology and signaling PNAS, November 30, 2004; 101(48): 16867 - 16872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-J. Chae, H.-K. Lee, J.-H. Han, S.-W. V. Kim, A. L.M. Bothwell, T. Morio, and S.-K. Lee Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor {zeta} chain ITAMs and their tyrosine residues Int. Immunol., September 1, 2004; 16(9): 1225 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Pitcher, P. S. Ohashi, and N. S. C. van Oers T Cell Antagonism is Functionally Uncoupled from the 21- and 23-kDa Tyrosine-Phosphorylated TCR {zeta} Subunits J. Immunol., July 15, 2003; 171(2): 845 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Y. Lin and M. R. Roberts Developmental dissociation of T cells from B, NK, and myeloid cells revealed by MHC class II-specific chimeric immune receptors bearing TCR-zeta or FcR-gamma chain signaling domains Blood, September 26, 2002; 100(8): 3045 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Haks, E. Pepin, J. H.N. van den Brakel, S. A.A. Smeele, S. M. Belkowski, H. W.H.G. Kessels, P. Krimpenfort, and A. M. Kruisbeek Contributions of the T Cell Receptor-associated CD3{gamma}-ITAM to Thymocyte Selection J. Exp. Med., July 1, 2002; 196(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Spain and P. Liu TCR{beta} Transmembrane Tyrosines Are Required for Pre-TCR Function J. Immunol., January 1, 2002; 168(1): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Mora, S. Stanley, W. Armistead, A. C. Chan, and M. Boothby Inefficient ZAP-70 Phosphorylation and Decreased Thymic Selection In Vivo Result from Inhibition of NF-{kappa}B/Rel J. Immunol., November 15, 2001; 167(10): 5628 - 5635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Azzam, J. B. DeJarnette, K. Huang, R. Emmons, C.-S. Park, C. L. Sommers, D. El-Khoury, E. W. Shores, and P. E. Love Fine Tuning of TCR Signaling by CD5 J. Immunol., May 1, 2001; 166(9): 5464 - 5472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Haks, T. A. Cordaro, J. H. N. van den Brakel, J. B. A. G. Haanen, E. F. R. de Vries, J. Borst, P. Krimpenfort, and A. M. Kruisbeek A Redundant Role of the CD3{{gamma}}-Immunoreceptor Tyrosine-Based Activation Motif in Mature T Cell Function J. Immunol., February 15, 2001; 166(4): 2576 - 2588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Sommers, J. B. Dejarnette, K. Huang, J. Lee, D. El-Khoury, E. W. Shores, and P. E. Love Function of Cd3{varepsilon}-Mediated Signals in T Cell Development J. Exp. Med., September 18, 2000; 192(6): 913 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Love, J. Lee, and E. W. Shores Critical Relationship Between TCR Signaling Potential and TCR Affinity During Thymocyte Selection J. Immunol., September 15, 2000; 165(6): 3080 - 3087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Nolan, C.-O. Yun, Y. Akamatsu, J. C. Murphy, S.-O. Leung, E. J. Beecham, and R. P. Junghans Bypassing Immunization: Optimized Design of ""Designer T Cells"" against Carcinoembryonic Antigen (CEA)-expressing Tumors, and Lack of Suppression by Soluble CEA Clin. Cancer Res., December 1, 1999; 5(12): 3928 - 3941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carleton, N. R. Ruetsch, M. A. Berger, M. Rhodes, S. Kaptik, and D. L. Wiest Signals Transduced by CD3{epsilon}, But Not by Surface Pre-TCR Complexes, Are Able to Induce Maturation of an Early Thymic Lymphoma In Vitro J. Immunol., September 1, 1999; 163(5): 2576 - 2585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zubiaur, M. Guirado, C. Terhorst, F. Malavasi, and J. Sancho The CD3-gamma delta epsilon Transducing Module Mediates CD38-induced Protein-tyrosine Kinase and Mitogen-activated Protein Kinase Activation in Jurkat T Cells J. Biol. Chem., July 16, 1999; 274(29): 20633 - 20642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Liu and D. A. A. Vignali Differential CD3{zeta} Phosphorylation Is Not Required for the Induction of T Cell Antagonism by Altered Peptide Ligands J. Immunol., July 15, 1999; 163(2): 599 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Geiger, D. Leitenberg, and R. A. Flavell The TCR {zeta}-Chain Immunoreceptor Tyrosine-Based Activation Motifs Are Sufficient for the Activation and Differentiation of Primary T Lymphocytes J. Immunol., May 15, 1999; 162(10): 5931 - 5939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Grassi, E. Barbier, S. Porcellini, H. von Boehmer, and P.-A. Cazenave Surface Expression and Functional Competence of CD3-Independent TCR {zeta}-Chains in Immature Thymocytes J. Immunol., March 1, 1999; 162(5): 2589 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Johansson, E. Palmer, and L. Bolliger The Extracellular Domain of the {zeta}-Chain Is Essential for TCR Function J. Immunol., January 15, 1999; 162(2): 878 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Kersh, A. S. Shaw, and P. M. Allen Fidelity of T Cell Activation Through Multistep T Cell Receptor  PhosphorylationScience, July 24, 1998; 281(5376): 572 - 575. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
