| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Immunopathology and
Immunology Units, GlaxoWellcome Medicines Research Centre, Stevenage, United Kingdom; and
Department of Molecular Sciences, Glaxo-Wellcome, Inc., Research Triangle Park, NC 27709
Adapter proteins such as Grb2 play a central role in the formation of signaling complexes through their association with multiple protein binding partners. These interactions are mediated by specialized domains such as the well-characterized Src homology SH2 and SH3 motifs. Using yeast three-hybrid technology, we have identified a novel adapter protein, expressed predominantly in T lymphocytes, that associates with the activated form of the costimulatory receptor, CD28. The protein is a member of the Grb2 family of adapter proteins and contains an SH3-SH2-SH3 domain structure. A unique glutamine/proline-rich domain (insert domain) of unknown function is situated between the SH2 and N-terminal SH3 domains. We term this protein GRID for Grb2-related protein with insert domain. GRID coimmunoprecipitates with CD28 from Jurkat cell lysates following activation of CD28. Using mutants of CD28 and GRID, we demonstrate that interaction between the proteins is dependent on phosphorylation of CD28 at tyrosine 173 and integrity of the GRID SH2 domain, although there are also subsidiary stabilizing contacts between the PXXP motifs of CD28 and the GRID C-terminal SH3 domain. In addition to CD28, GRID interacts with a number of other T cell signaling proteins, including SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa), p62dok, and RACK-1 (receptor for activated protein kinase C-1). These findings suggest that GRID functions as an adapter protein in the CD28-mediated costimulatory pathway in T cells.
This article has been cited by other articles:
|
|
 |
|
  S. Yamasaki, M. Takase-Utsugi, E. Ishikawa, M. Sakuma, K. Nishida, T. Saito, and O. Kanagawa Selective impairment of Fc{varepsilon}RI-mediated allergic reaction in Gads-deficient mice Int. Immunol., October 1, 2008; 20(10): 1289 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Garcon, D. T. Patton, J. L. Emery, E. Hirsch, R. Rottapel, T. Sasaki, and K. Okkenhaug CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer Blood, February 1, 2008; 111(3): 1464 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Tai, F. Van Laethem, A. H. Sharpe, and A. Singer Induction of autoimmune disease in CTLA-4 / mice depends on a specific CD28 motif that is required for in vivo costimulation PNAS, August 21, 2007; 104(34): 13756 - 13761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zeng, S. L. Dalheimer, and T. M. Yankee Gads-/- Mice Reveal Functionally Distinct Subsets of TCRbeta+ CD4-CD8- Double-Negative Thymocytes J. Immunol., July 15, 2007; 179(2): 1013 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Dennehy, F. Elias, S.-Y. Na, K.-D. Fischer, T. Hunig, and F. Luhder Mitogenic CD28 Signals Require the Exchange Factor Vav1 to Enhance TCR Signaling at the SLP-76-Vav-Itk Signalosome J. Immunol., February 1, 2007; 178(3): 1363 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Badour, M. K. H. McGavin, J. Zhang, S. Freeman, C. Vieira, D. Filipp, M. Julius, G. B. Mills, and K. A. Siminovitch Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells PNAS, January 30, 2007; 104(5): 1593 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Abtahian, N. Bezman, R. Clemens, E. Sebzda, L. Cheng, S. J. Shattil, M. L. Kahn, and G. A. Koretzky Evidence for the Requirement of ITAM Domains but Not SLP-76/Gads Interaction for Integrin Signaling in Hematopoietic Cells. Mol. Cell. Biol., September 1, 2006; 26(18): 6936 - 6949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Watanabe, Y. Harada, K. Takeda, J. Takahashi, K. Ohnuki, S. Ogawa, D. Ohgai, N. Kaibara, O. Koiwai, K. Tanabe, et al. Grb2 and Gads Exhibit Different Interactions with CD28 and Play Distinct Roles in CD28-Mediated Costimulation J. Immunol., July 15, 2006; 177(2): 1085 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Yankee, T. J. Yun, K. E. Draves, K. Ganesh, M. J. Bevan, K. Murali-Krishna, and E. A. Clark The Gads (GrpL) Adaptor Protein Regulates T Cell Homeostasis J. Immunol., August 1, 2004; 173(3): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Singer, S. C. Bunnell, A. E. Obstfeld, M. S. Jordan, J. N. Wu, P. S. Myung, L. E. Samelson, and G. A. Koretzky Roles of the Proline-rich Domain in SLP-76 Subcellular Localization and T Cell Function J. Biol. Chem., April 9, 2004; 279(15): 15481 - 15490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Cook, L. Albacker, A. August, and A. J. Henderson CD28-dependent HIV-1 Transcription Is Associated with Vav, Rac, and NF-{kappa}B Activation J. Biol. Chem., September 12, 2003; 278(37): 35812 - 35818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Parry, C. A. Rumbley, L. H. Vandenberghe, C. H. June, and J. L. Riley CD28 and Inducible Costimulatory Protein Src Homology 2 Binding Domains Show Distinct Regulation of Phosphatidylinositol 3-Kinase, Bcl-xL, and IL-2 Expression in Primary Human CD4 T Lymphocytes J. Immunol., July 1, 2003; 171(1): 166 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Dennehy, A. Kerstan, A. Bischof, J.-H. Park, S.-Y. Na, and T. Hunig Mitogenic signals through CD28 activate the protein kinase C{theta}-NF-{kappa}B pathway in primary peripheral T cells Int. Immunol., May 1, 2003; 15(5): 655 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yin, H. Schneider, and C. E. Rudd Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor J. Leukoc. Biol., January 1, 2003; 73(1): 178 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Yankee, S. A. Solow, K. D. Draves, and E. A. Clark Expression of the Grb2-Related Protein of the Lymphoid System in B Cell Subsets Enhances B Cell Antigen Receptor Signaling Through Mitogen-Activated Protein Kinase Pathways J. Immunol., January 1, 2003; 170(1): 349 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Martin, H. Schneider, A. Azouz, and C. E. Rudd Cytotoxic T Lymphocyte Antigen 4 and CD28 Modulate Cell Surface Raft Expression in Their Regulation of T Cell Function J. Exp. Med., December 3, 2001; 194(11): 1675 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yablonski, T. Kadlecek, and A. Weiss Identification of a Phospholipase C-{gamma}1 (PLC-{gamma}1) SH3 Domain-Binding Site in SLP-76 Required for T-Cell Receptor-Mediated Activation of PLC-{gamma}1 and NFAT Mol. Cell. Biol., July 1, 2001; 21(13): 4208 - 4218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kikuchi, Y. Kawasaki, N. Ishii, Y. Sasaki, H. Asao, T. Takeshita, I. Miyoshi, N. Kasai, and K. Sugamura Suppression of thymic development by the dominant-negative form of Gads Int. Immunol., June 1, 2001; 13(6): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
