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Pre-T Cell Receptor Signals Are Responsible for the Down-Regulation of Syk Protein Tyrosine Kinase Expression¹

David H. Chu^*, Nicolai S. C. van Oers^2,*, Marie Malissen^§, Jeff Harris, Melissa Elder and Arthur Weiss^3,*,

Departments of ^* Microbiology and Immunology, Pediatrics, and Medicine and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143; and ^§ Centre d’Immunologie Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique de Marseille-Luminy, Marseille, France

Thymocyte development proceeds through two critical checkpoints that involve signaling events through two different receptors, the TCR and the pre-TCR. These receptors employ two families of protein tyrosine kinases to propagate their signals, the Src and Syk families. Genetic and biochemical evidence has shown that the Src family kinases are critical for normal T cell maturation. ZAP-70, a Syk family kinase, has similarly been implicated as a critical component in thymocyte development. Although genetic evidence has suggested that Syk is involved during thymocyte development, a definitive study of Syk expression has not been performed. In this paper we report our reanalysis of Syk expression in subpopulations of murine and human thymocytes by intracellular staining and flow cytometry using anti-Syk mAbs. Syk is expressed at increased levels during the stages in which pre-TCR signaling occurs. Furthermore, Syk is down-regulated after the pre-TCR checkpoint has been passed. Syk may play an important role in thymic development during pre-TCR signal transduction. Finally, incomplete down-regulation of Syk expression was noted in human thymocytes, offering a possible explanation for the distinct phenotypes of mice and humans deficient in ZAP-70.

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