| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Gastroenterology Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115;
Department of Immunology, Imperial College, London, U.K.; and
Institute for Immunology, Charité-Humboldt University, Berlin, Germany
Carcinoembryonic Ag-related cellular adhesion molecule 1 (CEACAM1) represents a group of transmembrane protein isoforms that consist of variable numbers of extracellular Ig-like domains together with either a long cytoplasmic (cyt) tail containing two immunoreceptor tyrosine-based inhibitory motifs or a unique short cyt tail. Although CEACAM1 has been reported to be expressed on the surface of T lymphocytes upon activation, its roles in T cell regulation are controversial due to the lack of functional characterization of each individual CEACAM1 isoform. We thus cotransfected Jurkat T cells with CEACAM1 isoform-encoding constructs and an IL-2 promoter-bearing plasmid or a small interference RNA targeting src homology domain 2 containing phosphatase 1. In a luciferase reporter assay and through measurements of cytokine secretion (IL-2, IL-4, and IFN-
), CEACAM1 containing either a long or a short cyt tail inhibited or costimulated, respectively, TCR/CD3 complex plus CD28 mediated activation with the inhibitory functions of the long cyt tail dominating. The inhibitory function of CEACAM1, was dependent upon src homology domain 2 containing phosphatase 1 activity, required both tyrosine residues within the immunoreceptor tyrosine-based inhibitory motif domains of the cyt tail and was mediated through the mitogen-activated protein kinase pathway. CEACAM1-mediated inhibition could be functionally reconstituted by incubation of PBMC with either a CEACAM1-specific mAb or CEACAM1-Fc fusion protein in the presence of an allogeneic or mitogenic stimulus, respectively. These studies indicate that the long and short cyt tails of CEACAM1 serve as inhibitory and costimulatory receptors, respectively, in T cell regulation.
This article has been cited by other articles:
|
|
 |
|
  H. S. W. Lee, M. A. Ostrowski, and S. D. Gray-Owen CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation J. Immunol., May 15, 2008; 180(10): 6827 - 6835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, L. Chen, S.-W. Qiao, T. Nagaishi, and R. S. Blumberg Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70 J. Immunol., May 1, 2008; 180(9): 6085 - 6093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Monu and A. B. Frey Suppression of Proximal T Cell Receptor Signaling and Lytic Function in CD8+ Tumor-Infiltrating T Cells Cancer Res., December 1, 2007; 67(23): 11447 - 11454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. W. Lee, I. C. Boulton, K. Reddin, H. Wong, D. Halliwell, O. Mandelboim, A. R. Gorringe, and S. D. Gray-Owen Neisserial Outer Membrane Vesicles Bind the Coinhibitory Receptor Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 and Suppress CD4+ T Lymphocyte Function Infect. Immun., September 1, 2007; 75(9): 4449 - 4455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schmitter, S. Pils, V. Sakk, R. Frank, K.-D. Fischer, and C. R. Hauck The Granulocyte Receptor Carcinoembryonic Antigen-Related Cell Adhesion Molecule 3 (CEACAM3) Directly Associates with Vav to Promote Phagocytosis of Human Pathogens J. Immunol., March 15, 2007; 178(6): 3797 - 3805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Yu, E. M. C. Chow, H. Wong, J. Gu, O. Mandelboim, S. D. Gray-Owen, and M. A. Ostrowski CEACAM1 (CD66a) Promotes Human Monocyte Survival via a Phosphatidylinositol 3-Kinase- and AKT-dependent Pathway J. Biol. Chem., December 22, 2006; 281(51): 39179 - 39193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Albarran-Somoza, R. Franco-Topete, V. Delgado-Rizo, F. Cerda-Camacho, L. Acosta-Jimenez, M. Lopez-Botet, and A. Daneri-Navarro CEACAM1 in Cervical Cancer and Precursor Lesions: Association With Human Papillomavirus Infection J. Histochem. Cytochem., December 1, 2006; 54(12): 1393 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wang, Z. Li, R. Ding, G. D. Frank, T. Senbonmatsu, E. J. Landon, T. Inagami, and Z. J. Zhao Antagonism or Synergism: ROLE OF TYROSINE PHOSPHATASES SHP-1 AND SHP-2 IN GROWTH FACTOR SIGNALING J. Biol. Chem., August 4, 2006; 281(31): 21878 - 21883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-M. Bamberger, J. Briese, J. Gotze, I. Erdmann, H. M. Schulte, C. Wagener, and P. Nollau Stimulation of CEACAM1 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium ionophore A23187 in endometrial carcinoma cells Carcinogenesis, March 1, 2006; 27(3): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Azuz-Lieberman, G. Markel, S. Mizrahi, R. Gazit, J. Hanna, H. Achdout, R. Gruda, G. Katz, T. I. Arnon, S. Battat, et al. The involvement of NK cells in ankylosing spondylitis Int. Immunol., July 1, 2005; 17(7): 837 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Stern, G. Markel, T. I. Arnon, R. Gruda, H. Wong, S. D. Gray-Owen, and O. Mandelboim Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1 J. Immunol., June 1, 2005; 174(11): 6692 - 6701. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
