The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Truitt, K. E.
Right arrow Articles by Imboden, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Truitt, K. E.
Right arrow Articles by Imboden, J. B.

The Journal of Immunology, Vol 155, Issue 10 4702-4710, Copyright © 1995 by American Association of Immunologists

ARTICLES

CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase

KE Truitt, J Shi, S Gibson, LG Segal, GB Mills and JB Imboden
Department of Medicine, Veterans Affairs Medical Center, San Francisco, CA, USA.

CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28-mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.


This article has been cited by other articles:


Home page
 J. Immunol.Home page
A. J. de Souza, J. S. Oak, R. Jordanhazy, R. H. DeKruyff, D. A. Fruman, and L. P. Kane
T Cell Ig and Mucin Domain-1-Mediated T Cell Activation Requires Recruitment and Activation of Phosphoinositide 3-Kinase
J. Immunol., May 15, 2008; 180(10): 6518 - 6526.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. A. Deane, M. G. Kharas, J. S. Oak, L. N. Stiles, J. Luo, T. I. Moore, H. Ji, C. Rommel, L. C. Cantley, T. E. Lane, et al.
T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling
Blood, April 1, 2007; 109(7): 2894 - 2902.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Arimura, F. Shiroki, S. Kuwahara, H. Kato, U. Dianzani, T. Uchiyama, and J. Yagi
Akt Is a Neutral Amplifier for Th Cell Differentiation
J. Biol. Chem., March 19, 2004; 279(12): 11408 - 11416.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L.-W. Fang, T.-S. Tai, W.-N. Yu, F. Liao, and M.-Z. Lai
Phosphatidylinositide 3-Kinase Priming Couples c-FLIP to T Cell Activation
J. Biol. Chem., January 2, 2004; 279(1): 13 - 18.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 J. Leukoc. Biol.Home page
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]

Home page
 BloodHome page
P. Ghosh, M. A. Buchholz, S. Yano, D. Taub, and D. L. Longo
Effect of rapamycin on the cyclosporin A-resistant CD28-mediated costimulatory pathway
Blood, May 29, 2002; 99(12): 4517 - 4524.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
V. S. Shapiro, M. N. Mollenauer, and A. Weiss
Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression
Blood, July 1, 2001; 98(1): 187 - 193.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Harada, M. Tokushima, Y. Matsumoto, S. Ogawa, M. Otsuka, K. Hayashi, B. D. Weiss, C. H. June, and R. Abe
Critical Requirement for the Membrane-Proximal Cytosolic Tyrosine Residue for CD28-Mediated Costimulation In Vivo
J. Immunol., March 15, 2001; 166(6): 3797 - 3803.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C.-T. Yu, H.-m. Shih, and M.-Z. Lai
Multiple Signals Required for Cyclic AMP-Responsive Element Binding Protein (CREB) Binding Protein Interaction Induced by CD3/CD28 Costimulation
J. Immunol., January 1, 2001; 166(1): 284 - 292.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 Mol. Cell. Biol.Home page
X. Shan, M. J. Czar, S. C. Bunnell, P. Liu, Y. Liu, P. L. Schwartzberg, and R. L. Wange
Deficiency of PTEN in Jurkat T Cells Causes Constitutive Localization of Itk to the Plasma Membrane and Hyperresponsiveness to CD3 Stimulation
Mol. Cell. Biol., September 15, 2000; 20(18): 6945 - 6957.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
T. Cinek, A. Sadra, and J. B. Imboden
Cutting Edge: Tyrosine-Independent Transmission of Inhibitory Signals by CTLA-4
J. Immunol., January 1, 2000; 164(1): 5 - 8.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. Oki, T. Kohsaka, and M. Azuma
Augmentation of CTLA-4 expression by wortmannin: involvement of lysosomal sorting properties of CTLA-4
Int. Immunol., September 1, 1999; 11(9): 1563 - 1571.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
H. GUDMUNDSDOTTIR and L. A. TURKA
T Cell Costimulatory Blockade: New Therapies for TransplantRejection
J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1356 - 1365.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
A. Sadra, T. Cinek, J. L. Arellano, J. Shi, K. E. Truitt, and J. B. Imboden
Identification of Tyrosine Phosphorylation Sites in the CD28 Cytoplasmic Domain and Their Role in the Costimulation of Jurkat T Cells
J. Immunol., February 15, 1999; 162(4): 1966 - 1973.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. E. Sedwick, M. M. Morgan, L. Jusino, J. L. Cannon, J. Miller, and J. K. Burkhardt
TCR, LFA-1, and CD28 Play Unique and Complementary Roles in Signaling T Cell Cytoskeletal Reorganization
J. Immunol., February 1, 1999; 162(3): 1367 - 1375.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
D. A. Fruman, S. B. Snapper, C. M. Yballe, L. Davidson, J. Y. Yu, F. W. Alt, and L. C. Cantley
Impaired B Cell Development and Proliferation in Absence of Phosphoinositide 3-Kinase p85
Science, January 15, 1999; 283(5400): 393 - 397.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
C. Barz, T. Nagel, K. E. Truitt, and J. B. Imboden
Mutational Analysis of CD28-Mediated Costimulation of Jun-N-Terminal Kinase and IL-2 Production
J. Immunol., November 15, 1998; 161(10): 5366 - 5372.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Lu, B. Cuevas, S. Gibson, H. Khan, R. LaPushin, J. Imboden, and G. B. Mills
Phosphatidylinositol 3-Kinase Is Required for CD28 But Not CD3 Regulation of the TEC Family Tyrosine Kinase EMT/ITK/TSK: Functional and Physical Interaction of EMT with Phosphatidylinositol 3-Kinase
J. Immunol., November 15, 1998; 161(10): 5404 - 5412.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. M. Eder, L. Dominguez, T. F. Franke, and J. D. Ashwell
Phosphoinositide 3-Kinase Regulation of T Cell Receptor-mediated Interleukin-2 Gene Expression in Normal T Cells
J. Biol. Chem., October 23, 1998; 273(43): 28025 - 28031.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Porcu, J. Gaddy, and H. E. Broxmeyer
Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated with defective activation of Ras
PNAS, April 14, 1998; 95(8): 4538 - 4543.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Cefai, H. Schneider, O. Matangkasombut, H. Kang, J. Brody, and C. E. Rudd
CD28 Receptor Endocytosis Is Targeted by Mutations That Disrupt Phosphatidylinositol 3-Kinase Binding and Costimulation
J. Immunol., March 1, 1998; 160(5): 2223 - 2230.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
X. C. Liao, S. Fournier, N. Killeen, A. Weiss, J. P. Allison, and D. R. Littman
Itk Negatively Regulates Induction of  T Cell Proliferation by CD28 Costimulation
J. Exp. Med., July 21, 1997; 186(2): 221 - 228.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F.ço. Pagès, M. Ragueneau, S. Klasen, M. Battifora, D. Couez, R. Sweet, A. Truneh, S. G. Ward, and D. Olive
Two Distinct Intracytoplasmic Regions of the T-cell Adhesion Molecule CD28 Participate in Phosphatidylinositol 3-Kinase Association
J. Biol. Chem., April 19, 1996; 271(16): 9403 - 9409.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Harada, E. Tanabe, R. Watanabe, B. D. Weiss, A. Matsumoto, H. Ariga, O. Koiwai, Y. Fukui, M. Kubo, C. H. June, et al.
Novel Role of Phosphatidylinositol 3-Kinase in CD28-mediated Costimulation
J. Biol. Chem., March 16, 2001; 276(12): 9003 - 9008.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Kang, H. Schneider, and C. E. Rudd
Phosphatidylinositol 3-Kinase p85 Adaptor Function in T-cells. CO-STIMULATION AND REGULATION OF CYTOKINE TRANSCRIPTION INDEPENDENT OF ASSOCIATED p110
J. Biol. Chem., January 4, 2002; 277(2): 912 - 921.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1995 by The American Association of Immunologists, Inc. All rights reserved.