| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
/CD3 Complex, But Not CD28, Interact with Clathrin Adaptor Complexes AP-1 and AP-2
,||,||
*
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115;
Sackler School of Biomedical Sciences, Tufts University, and
Center for Blood Research, and Departments of
§
Medicine,
¶
Pathology, and
||
Cell Biology, Harvard Medical School, Boston, MA 02115
The negative signaling receptor cytolytic T lymphocyte-associated
Ag-4 (CTLA-4) resides primarily in intracellular compartments such as
the Golgi apparatus of T cells. However, little is known regarding the
molecular mechanisms that influence this accumulation. In this study,
we demonstrate binding of the clathrin adaptor complex AP-1 with the
GVYVKM motif of the cytoplasmic domain of CTLA-4. Binding occurred
primarily in the Golgi compartment of T cells, unlike with AP-2 binding
that occurs mostly with cell surface CTLA-4. Although evidence was not
found to implicate AP-1 binding in the retention of CTLA-4 in the
Golgi, AP-1 appears to play a role in shuttling of excess receptor from
the Golgi to the lysosomal compartments for degradation. In support of
this, increased CTLA-4 synthesis resulted in an increase in CTLA-4/AP-1
binding and a concomitant increase in the appearance of CTLA-4 in the
lysosomal compartment. At the same time, the level of intracellular
receptor was maintained at a constant level, suggesting that
CTLA-4/AP-1 binding represents one mechanism to ensure steady state
levels of intracellular CTLA-4 in T cells. Finally, we demonstrate that
the TCR
/CD3 complex (but not CD28) also binds to AP-1 and AP-2
complexes, thus providing a possible link between these two receptors
in the regulation of T cell function.
This article has been cited by other articles:
|
|
 |
|
  M. Berg and N. Zavazava Regulation of CD28 expression on CD8+ T cells by CTLA-4 J. Leukoc. Biol., April 1, 2008; 83(4): 853 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wei, S. da Rocha Dias, H. Wang, and C. E. Rudd CTL-Associated Antigen-4 Ligation Induces Rapid T Cell Polarization That Depends on Phosphatidylinositol 3-Kinase, Vav-1, Cdc42, and Myosin Light Chain Kinase J. Immunol., July 1, 2007; 179(1): 400 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Bernard, B. Riteau, J. D. Hansen, R. B. Phillips, F. Michel, P. Boudinot, and A. Benmansour Costimulatory Receptors in a Teleost Fish: Typical CD28, Elusive CTLA4 J. Immunol., April 1, 2006; 176(7): 4191 - 4200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lundholm, V. Motta, A. Lofgren-Burstrom, N. Duarte, M.-L. Bergman, S. Mayans, and D. Holmberg Defective Induction of CTLA-4 in the NOD Mouse Is Controlled by the NOD Allele of Idd3/IL-2 and a Novel Locus (Ctex) Telomeric on Chromosome 1 Diabetes, February 1, 2006; 55(2): 538 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Schneider, E. Valk, S. da Rocha Dias, B. Wei, and C. E. Rudd CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function PNAS, September 6, 2005; 102(36): 12861 - 12866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. I. Mead, Y. Zheng, C. N. Manzotti, L. C. A. Perry, M. K. P. Liu, F. Burke, D. J. Powner, M. J. O. Wakelam, and D. M. Sansom Exocytosis of CTLA-4 Is Dependent on Phospholipase D and ADP Ribosylation Factor-1 and Stimulated during Activation of Regulatory T Cells J. Immunol., April 15, 2005; 174(8): 4803 - 4811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Szymczak and D. A. A. Vignali Plasticity and Rigidity in Adaptor Protein-2-Mediated Internalization of the TCR:CD3 Complex J. Immunol., April 1, 2005; 174(7): 4153 - 4160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Yi, S. Hajialiasgar, and E. Chuang Tyrosine-mediated inhibitory signals contribute to CTLA-4 function in vivo Int. Immunol., April 1, 2004; 16(4): 539 - 547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Putnam, A. E. Moquin, M. Merrihew, C. Outcalt, E. Sorge, A. Caballero, T. A. Gondre-Lewis, and J. R. Drake Lipid Raft-Independent B Cell Receptor-Mediated Antigen Internalization and Intracellular Trafficking J. Immunol., January 15, 2003; 170(2): 905 - 912. [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]
|
|
|
|
 |
|
 M. P. Pistillo, P. L. Tazzari, G. L. Palmisano, I. Pierri, A. Bolognesi, F. Ferlito, P. Capanni, L. Polito, M. Ratta, S. Pileri, et al. CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells Blood, January 1, 2003; 101(1): 202 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Schneider, D. A. Mandelbrot, R. J. Greenwald, F. Ng, R. Lechler, A. H. Sharpe, and C. E. Rudd Cutting Edge: CTLA-4 (CD152) Differentially Regulates Mitogen-Activated Protein Kinases (Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase) in CD4+ T Cells from Receptor/Ligand-Deficient Mice J. Immunol., October 1, 2002; 169(7): 3475 - 3479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chikuma and J. A. Bluestone CTLA-4: Acting at the Synapse Mol. Interv., July 1, 2002; 2(4): 205 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakajima, H. Iijima, M. F. Neurath, T. Nagaishi, E. E. S. Nieuwenhuis, R. Raychowdhury, J. Glickman, D. M. Blau, S. Russell, K. V. Holmes, et al. Activation-Induced Expression of Carcinoembryonic Antigen-Cell Adhesion Molecule 1 Regulates Mouse T Lymphocyte Function J. Immunol., February 1, 2002; 168(3): 1028 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. da Rocha Dias and C. E. Rudd CTLA-4 blockade of antigen-induced cell death Blood, February 15, 2001; 97(4): 1134 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Iida, H. Ohno, C. Nakaseko, M. Sakuma, M. Takeda-Ezaki, H. Arase, E. Kominami, T. Fujisawa, and T. Saito Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells J. Immunol., November 1, 2000; 165(9): 5062 - 5068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Qadri, C. G. Radu, J. Thatte, P. Cianga, B. T. Ober, R. J. Ober, and E. S. Ward A Role for the Region Encompassing the c'' Strand of a TCR V{alpha} Domain in T Cell Activation Events J. Immunol., July 15, 2000; 165(2): 820 - 829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Masteller, E. Chuang, A. C. Mullen, S. L. Reiner, and C. B. Thompson Structural Analysis of CTLA-4 Function In Vivo J. Immunol., May 15, 2000; 164(10): 5319 - 5327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
