Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 291 (5510): 1987-1991

Copyright © 2001 by the American Association for the Advancement of Science

Requirement for the SLP-76 Adaptor GADS in T Cell Development

Jeff Yoder,1 Christine Pham,234 Yoshie-Matsubayashi Iizuka,3 Osami Kanagawa,4 Stanley K. Liu,5 Jane McGlade,5 Alec M. Cheng234*

GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling.

1 Medical Scientist Training Program;
2 Center for Immunology;
3 Division of Rheumatology, Department of Medicine;
4 Department of Pathology and Immunology; Washington University School of Medicine, St. Louis, MO 63110, USA.
5 Hospital for the Sick Children, University of Toronto, Toronto, Canada.
*   To whom correspondence should be addressed. E-mail:acheng{at}im.wustl.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SLP-76 Sterile {alpha} Motif (SAM) and Individual H5 {alpha} Helix Mediate Oligomer Formation for Microclusters and T-cell Activation.
H. Liu, Y. R. Thaker, L. Stagg, H. Schneider, J. E. Ladbury, and C. E. Rudd (2013)
J. Biol. Chem. 288, 29539-29549
   Abstract »    Full Text »    PDF »
The Importance of the Erk Pathway in the Development of Linker for Activation of T Cells-Mediated Autoimmunity.
D. M. Fuller, M. Zhu, S. Koonpaew, M. I. Nelson, and W. Zhang (2012)
J. Immunol. 189, 4005-4013
   Abstract »    Full Text »    PDF »
Evolution of SH2 domains and phosphotyrosine signalling networks.
B. A. Liu and P. D. Nash (2012)
Phil Trans R Soc B 367, 2556-2573
   Abstract »    Full Text »    PDF »
The SH2 Domain-Containing Proteins in 21 Species Establish the Provenance and Scope of Phosphotyrosine Signaling in Eukaryotes.
B. A. Liu, E. Shah, K. Jablonowski, A. Stergachis, B. Engelmann, and P. D. Nash (2011)
Science Signaling 4, ra83
   Abstract »    Full Text »    PDF »
Gads Regulates the Expansion Phase of CD8+ T Cell-Mediated Immunity.
E. Y. Zhang, B. L. Parker, and T. M. Yankee (2011)
J. Immunol. 186, 4579-4589
   Abstract »    Full Text »    PDF »
Fas Apoptosis Inhibitory Molecule Regulates T Cell Receptor-mediated Apoptosis of Thymocytes by Modulating Akt Activation and Nur77 Expression.
J. Huo, S. Xu, and K. P. Lam (2010)
J. Biol. Chem. 285, 11827-11835
   Abstract »    Full Text »    PDF »
SLP-76 Couples Syk to the Osteoclast Cytoskeleton.
J. L. Reeve, W. Zou, Y. Liu, J. S. Maltzman, F. P. Ross, and S. L. Teitelbaum (2009)
J. Immunol. 183, 1804-1812
   Abstract »    Full Text »    PDF »
The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-{alpha} motif domain in thymic selection and T-cell activation.
S. Shen, J. Lau, M. Zhu, J. Zou, D. Fuller, Q.-j. Li, and W. Zhang (2009)
Blood 114, 74-84
   Abstract »    Full Text »    PDF »
Cutting Edge: Rescue of Pre-TCR but Not Mature TCR Signaling in Mice Expressing Membrane-Targeted SLP-76.
N. A. Bezman, R. G. Baker, L. E. Lenox, M. S. Jordan, and G. A. Koretzky (2009)
J. Immunol. 182, 5183-5187
   Abstract »    Full Text »    PDF »
Origin of the sharp boundary that discriminates positive and negative selection of thymocytes.
A. Prasad, J. Zikherman, J. Das, J. P. Roose, A. Weiss, and A. K. Chakraborty (2009)
PNAS 106, 528-533
   Abstract »    Full Text »    PDF »
Selective impairment of Fc{varepsilon}RI-mediated allergic reaction in Gads-deficient mice.
S. Yamasaki, M. Takase-Utsugi, E. Ishikawa, M. Sakuma, K. Nishida, T. Saito, and O. Kanagawa (2008)
Int. Immunol. 20, 1289-1297
   Abstract »    Full Text »    PDF »
Impaired thymic selection in mice expressing altered levels of the SLP-76 adaptor protein.
K. Ramsey, N. Luckashenak, G. A. Koretzky, and J. L. Clements (2008)
J. Leukoc. Biol. 83, 419-429
   Abstract »    Full Text »    PDF »
Subtle Defects in Pre-TCR Signaling in the Absence of the Tec Kinase Itk.
J. A. Lucas, M. Felices, J. W. Evans, and L. J. Berg (2007)
J. Immunol. 179, 7561-7567
   Abstract »    Full Text »    PDF »
Gads-/- Mice Reveal Functionally Distinct Subsets of TCR{beta}+ CD4-CD8- Double-Negative Thymocytes.
L. Zeng, S. L. Dalheimer, and T. M. Yankee (2007)
J. Immunol. 179, 1013-1021
   Abstract »    Full Text »    PDF »
LAT and NTAL Mediate Immunoglobulin E-Induced Sustained Extracellular Signal-Regulated Kinase Activation Critical for Mast Cell Survival.
S. Yamasaki, E. Ishikawa, M. Sakuma, O. Kanagawa, A. M. Cheng, B. Malissen, and T. Saito (2007)
Mol. Cell. Biol. 27, 4406-4415
   Abstract »    Full Text »    PDF »
Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif.
B. T. Seet, D. M. Berry, J. S. Maltzman, J. Shabason, M. Raina, G. A. Koretzky, C. J. McGlade, and T. Pawson (2007)
EMBO J. 26, 678-689
   Abstract »    Full Text »    PDF »
Oncogenic role of Pax5 in the T-lymphoid lineage upon ectopic expression from the immunoglobulin heavy-chain locus.
A. Souabni, W. Jochum, and M. Busslinger (2007)
Blood 109, 281-289
   Abstract »    Full Text »    PDF »
ShcA Mediates the Dominant Pathway to Extracellular Signal-Regulated Kinase Activation during Early Thymic Development.
P. Trampont, L. Zhang, and K. S. Ravichandran (2006)
Mol. Cell. Biol. 26, 9035-9044
   Abstract »    Full Text »    PDF »
Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes.
A. Grabbe and J. Wienands (2006)
Blood 108, 3761-3768
   Abstract »    Full Text »    PDF »
Grb2 and Gads Exhibit Different Interactions with CD28 and Play Distinct Roles in CD28-Mediated Costimulation.
R. Watanabe, Y. Harada, K. Takeda, J. Takahashi, K. Ohnuki, S. Ogawa, D. Ohgai, N. Kaibara, O. Koiwai, K. Tanabe, et al. (2006)
J. Immunol. 177, 1085-1091
   Abstract »    Full Text »    PDF »
Adhesion- and Degranulation-Promoting Adapter Protein Is Required for Efficient Thymocyte Development and Selection.
J. N. Wu, S. Gheith, N. A. Bezman, Q.-H. Liu, L. V. Fostel, A. M. Swanson, B. D. Freedman, G. A. Koretzky, and E. J. Peterson (2006)
J. Immunol. 176, 6681-6689
   Abstract »    Full Text »    PDF »
A Role for MAPK in Feedback Inhibition of Tcrb Recombination.
A. M. Jackson and M. S. Krangel (2006)
J. Immunol. 176, 6824-6830
   Abstract »    Full Text »    PDF »
Disruption of SLP-76 Interaction with Gads Inhibits Dynamic Clustering of SLP-76 and Fc{varepsilon}RI Signaling in Mast Cells.
M. A. Silverman, J. Shoag, J. Wu, and G. A. Koretzky (2006)
Mol. Cell. Biol. 26, 1826-1838
   Abstract »    Full Text »    PDF »
T Cell Receptor-induced Activation of Phospholipase C-{gamma}1 Depends on a Sequence-independent Function of the P-I Region of SLP-76.
R. Gonen, D. Beach, C. Ainey, and D. Yablonski (2005)
J. Biol. Chem. 280, 8364-8370
   Abstract »    Full Text »    PDF »
The Gads (GrpL) Adaptor Protein Regulates T Cell Homeostasis.
T. M. Yankee, T. J. Yun, K. E. Draves, K. Ganesh, M. J. Bevan, K. Murali-Krishna, and E. A. Clark (2004)
J. Immunol. 173, 1711-1720
   Abstract »    Full Text »    PDF »
Roles of the Proline-rich Domain in SLP-76 Subcellular Localization and T Cell Function.
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 (2004)
J. Biol. Chem. 279, 15481-15490
   Abstract »    Full Text »    PDF »
Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads.
S. Cho, C. A. Velikovsky, C. P. Swaminathan, J. C. Houtman, L. E. Samelson, and R. A. Mariuzza (2004)
EMBO J. 23, 1441-1451
   Abstract »    Full Text »    PDF »
The Importance of Three Membrane-distal Tyrosines in the Adaptor Protein NTAL/LAB.
S. Koonpaew, E. Janssen, M. Zhu, and W. Zhang (2004)
J. Biol. Chem. 279, 11229-11235
   Abstract »    Full Text »    PDF »
Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76.
M. Harkiolaki, M. Lewitzky, R. J. C. Gilbert, E. Jones, R. P. Bourette, G. Mouchiroud, H. Sondermann, I. Moarefi, and S. M. Feller (2003)
EMBO J. 22, 2571-2582
   Abstract »    Full Text »    PDF »
Gab3-Deficient Mice Exhibit Normal Development and Hematopoiesis and Are Immunocompetent.
M. Seiffert, J. M. Custodio, I. Wolf, M. Harkey, Y. Liu, J. N. Blattman, P. D. Greenberg, and L. R. Rohrschneider (2003)
Mol. Cell. Biol. 23, 2415-2424
   Abstract »    Full Text »    PDF »
Gads/Grb2-Mediated Association with LAT Is Critical for the Inhibitory Function of Gab2 in T Cells.
S. Yamasaki, K. Nishida, M. Sakuma, D. Berry, C. J. McGlade, T. Hirano, and T. Saito (2003)
Mol. Cell. Biol. 23, 2515-2529
   Abstract »    Full Text »    PDF »
Signaling Life and Death in the Thymus: Timing Is Everything.
G. Werlen, B. Hausmann, D. Naeher, and E. Palmer (2003)
Science 299, 1859-1863
   Abstract »    Full Text »    PDF »
Growth Factor Independence-1B Expression Leads to Defects in T Cell Activation, IL-7 Receptor {alpha} Expression, and T Cell Lineage Commitment.
L. L. Doan, M. K. Kitay, Q. Yu, A. Singer, S. Herblot, T. Hoang, S. E. Bear, H. C. Morse III, P. N. Tsichlis, and H. L. Grimes (2003)
J. Immunol. 170, 2356-2366
   Abstract »    Full Text »    PDF »
Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML-1 transcription factor.
B. Guyot and G. Mouchiroud (2003)
J. Leukoc. Biol. 73, 263-272
   Abstract »    Full Text »    PDF »
Minimal Requirement of Tyrosine Residues of Linker for Activation of T Cells in TCR Signaling and Thymocyte Development.
M. Zhu, E. Janssen, and W. Zhang (2003)
J. Immunol. 170, 325-333
   Abstract »    Full Text »    PDF »
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.
T. M. Yankee, S. A. Solow, K. D. Draves, and E. A. Clark (2003)
J. Immunol. 170, 349-355
   Abstract »    Full Text »    PDF »
Molecular Cloning of a Novel Gene Encoding a Membrane-associated Adaptor Protein (LAX) in Lymphocyte Signaling.
M. Zhu, E. Janssen, K. Leung, and W. Zhang (2002)
J. Biol. Chem. 277, 46151-46158
   Abstract »    Full Text »    PDF »
Prevention of Thymic Lymphoma Development in Atm-/- Mice by Dexamethasone.
M. Yan, X. Kuang, W. Qiang, J. Shen, K. Claypool, W. S. Lynn, and P. K. Y. Wong (2002)
Cancer Res. 62, 5153-5157
   Abstract »    Full Text »    PDF »
Regulation of T Cell Receptor-induced Activation of the Ras-ERK Pathway by Diacylglycerol Kinase zeta.
X.-P. Zhong, E. A. Hainey, B. A. Olenchock, H. Zhao, M. K. Topham, and G. A. Koretzky (2002)
J. Biol. Chem. 277, 31089-31098
   Abstract »    Full Text »    PDF »
Dok-related protein negatively regulates T cell development via its RasGTPase-activating protein and Nck docking sites.
R. Gugasyan, C. Quilici, S. T.T. I, D. Grail, A. M. Verhagen, A. Roberts, T. Kitamura, A. R. Dunn, and P. Lock (2002)
J. Cell Biol. 158, 115-125
   Abstract »    Full Text »    PDF »
Induced Expression and Association of the Mona/Gads Adapter and Gab3 Scaffolding Protein during Monocyte/Macrophage Differentiation.
C. Bourgin, R. P. Bourette, S. Arnaud, Y. Liu, L. R. Rohrschneider, and G. Mouchiroud (2002)
Mol. Cell. Biol. 22, 3744-3756
   Abstract »    Full Text »    PDF »
Grap Negatively Regulates T-Cell Receptor-Elicited Lymphocyte Proliferation and Interleukin-2 Induction.
R. Shen, Y.-B. Ouyang, C.-K. Qu, A. Alonso, L. Sperzel, T. Mustelin, M. H. Kaplan, and G.-S. Feng (2002)
Mol. Cell. Biol. 22, 3230-3236
   Abstract »    Full Text »    PDF »
Differential Requirement for LAT and SLP-76 in GPVI versus T Cell Receptor Signaling.
B. A. Judd, P. S. Myung, A. Obergfell, E. E. Myers, A. M. Cheng, S. P. Watson, W. S. Pear, D. Allman, S. J. Shattil, and G. A. Koretzky (2002)
J. Exp. Med. 195, 705-717
   Abstract »    Full Text »    PDF »
Differential SLP-76 Expression and TCR-Mediated Signaling in Effector and Memory CD4 T Cells.
S. F. Hussain, C. F. Anderson, and D. L. Farber (2002)
J. Immunol. 168, 1557-1565
   Abstract »    Full Text »    PDF »
TCR{beta} Transmembrane Tyrosines Are Required for Pre-TCR Function.
L. M. Spain and P. Liu (2002)
J. Immunol. 168, 127-133
   Abstract »    Full Text »    PDF »
Loss of Neurons in the Hippocampus and Cerebral Cortex of AMSH-Deficient Mice.
N. Ishii, Y. Owada, M. Yamada, S. Miura, K. Murata, H. Asao, H. Kondo, and K. Sugamura (2001)
Mol. Cell. Biol. 21, 8626-8637
   Abstract »    Full Text »    PDF »
Membrane Raft-Dependent Regulation of Phospholipase C{gamma}-1 Activation in T Lymphocytes.
M.-C. Veri, K. E. DeBell, M.-C. Seminario, A. DiBaldassarre, I. Reischl, R. Rawat, L. Graham, C. Noviello, B. L. Rellahan, S. Miscia, et al. (2001)
Mol. Cell. Biol. 21, 6939-6950
   Abstract »    Full Text »    PDF »
Identification of the Minimal Tyrosine Residues Required for Linker for Activation of T Cell Function.
J. Lin and A. Weiss (2001)
J. Biol. Chem. 276, 29588-29595
   Abstract »    Full Text »    PDF »
Identification of the minimal tyrosine residues required for LAT function.
J. Lin and A. Weiss (2001)
J. Biol. Chem.
   Abstract »    PDF »
Docking Protein Gab2 Is Phosphorylated by ZAP-70 and Negatively Regulates T Cell Receptor Signaling by Recruitment of Inhibitory Molecules.
S. Yamasaki, K. Nishida, M. Hibi, M. Sakuma, R. Shiina, A. Takeuchi, H. Ohnishi, T. Hirano, and T. Saito (2001)
J. Biol. Chem. 276, 45175-45183
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882