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CUTTING EDGE |
*
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA; and
Center for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women’s and Children’s Hospital, Adelaide, Australia
The genetic defect in X-linked lymphoproliferative syndrome (XLP) is the Src homology 2 domain-containing protein SAP. SAP constitutively associates with the cell surface molecule, signaling lymphocytic activation molecule (SLAM), and competes with SH2-domain containing protein tyrosine phosphatase-2 (SHP-2) for recruitment to SLAM. SLAM exhibits homology with the mouse cell surface receptor 2B4. The human homologue of 2B4 has now been identified. It is recognized by the c1.7 mAb, a mAb capable of activating human NK cells. Human 2B4 became tyrosine phosphorylated following pervanadate-treatment of transfected cells and recruited SHP-2. SAP was also recruited to 2B4 in activated cells. Importantly, the 2B4-SAP interaction prevented the association between 2B4 and SHP-2. These results suggest that the phenotype of XLP may result from perturbed signaling not only through SLAM, but also other cell surface molecules that utilize SAP as a signaling adaptor protein.
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S. Parolini, C. Bottino, M. Falco, R. Augugliaro, S. Giliani, R. Franceschini, H. D. Ochs, H. Wolf, J.-Y. Bonnefoy, R. Biassoni, et al. X-Linked Lymphoproliferative Disease: 2b4 Molecules Displaying Inhibitory Rather than Activating Function Are Responsible for the Inability of Natural Killer Cells to Kill Epstein-Barr Virus-Infected Cells J. Exp. Med., August 7, 2000; 192(3): 337 - 346. [Abstract] [Full Text] [PDF]
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N. Fournier, L. Chalus, I. Durand, E. Garcia, J.-J. Pin, T. Churakova, S. Patel, C. Zlot, D. Gorman, S. Zurawski, et al. FDF03, a Novel Inhibitory Receptor of the Immunoglobulin Superfamily, Is Expressed by Human Dendritic and Myeloid Cells J. Immunol., August 1, 2000; 165(3): 1197 - 1209. [Abstract] [Full Text] [PDF]
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L. L. Lanier Turning on Natural Killer Cells J. Exp. Med., April 17, 2000; 191(8): 1259 - 1262. [Full Text] [PDF]
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D. D. Mousseau, D. Banville, D. L'Abbe, P. Bouchard, and S.-H. Shen PILRalpha , a Novel Immunoreceptor Tyrosine-based Inhibitory Motif-bearing Protein, Recruits SHP-1 upon Tyrosine Phosphorylation and Is Paired with the Truncated Counterpart PILRbeta J. Biol. Chem., February 11, 2000; 275(6): 4467 - 4474. [Abstract] [Full Text] [PDF]
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A. G. Castro, T. M. Hauser, B. G. Cocks, J. Abrams, S. Zurawski, T. Churakova, F. Zonin, D. Robinson, S. G. Tangye, G. Aversa, et al. Molecular and Functional Characterization of Mouse Signaling Lymphocytic Activation Molecule (SLAM): Differential Expression and Responsiveness in Th1 and Th2 Cells J. Immunol., December 1, 1999; 163(11): 5860 - 5870. [Abstract] [Full Text] [PDF]
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T. Angata and A. Varki Cloning, Characterization, and Phylogenetic Analysis of Siglec-9, a New Member of the CD33-related Group of Siglecs. EVIDENCE FOR CO-EVOLUTION WITH SIALIC ACID SYNTHESIS PATHWAYS J. Biol. Chem., July 14, 2000; 275(29): 22127 - 22135. [Abstract] [Full Text] [PDF]
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N. Mavaddat, D. W. Mason, P. D. Atkinson, E. J. Evans, R. J. C. Gilbert, D. I. Stuart, J. A. Fennelly, A. N. Barclay, S. J. Davis, and M. H. Brown Signaling Lymphocytic Activation Molecule (CDw150) Is Homophilic but Self-associates with Very Low Affinity J. Biol. Chem., September 1, 2000; 275(36): 28100 - 28109. [Abstract] [Full Text] [PDF]
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T. Ulyanova, D. D. Shah, and M. L. Thomas Molecular Cloning of MIS, a Myeloid Inhibitory Siglec, That Binds Protein-tyrosine Phosphatases SHP-1 and SHP-2 J. Biol. Chem., April 20, 2001; 276(17): 14451 - 14458. [Abstract] [Full Text] [PDF]
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M. Morra, M. Simarro-Grande, M. Martin, A. S.-I. Chen, A. Lanyi, O. Silander, S. Calpe, J. Davis, T. Pawson, M. J. Eck, et al. Characterization of SH2D1A Missense Mutations Identified in X-linked Lymphoproliferative Disease Patients J. Biol. Chem., September 21, 2001; 276(39): 36809 - 36816. [Abstract] [Full Text] [PDF]
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Z. Yu, C.-M. Lai, M. Maoui, D. Banville, and S.-H. Shen Identification and Characterization of S2V, a Novel Putative Siglec That Contains Two V Set Ig-like Domains and Recruits Protein-tyrosine Phosphatases SHPs J. Biol. Chem., June 22, 2001; 276(26): 23816 - 23824. [Abstract] [Full Text] [PDF]
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B. S. Sylla, K. Murphy, E. Cahir-McFarland, W. S. Lane, G. Mosialos, and E. Kieff The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B PNAS, June 20, 2000; 97(13): 7470 - 7475. [Abstract] [Full Text] [PDF]
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M. J. Czar, E. N. Kersh, L. A. Mijares, G. Lanier, J. Lewis, G. Yap, A. Chen, A. Sher, C. S. Duckett, R. Ahmed, et al. Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP PNAS, June 19, 2001; 98(13): 7449 - 7454. [Abstract] [Full Text] [PDF]
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