Pre-T cell receptor signals are responsible for the down-regulation of Sykprotein tyrosine kinase expression

Thymocyte development proceeds through two critical checkpoints that involv e signaling events through two different receptors, the TCR and the pre-TCR , These receptors employ two families of protein tyrosine kinases to propag ate their signals, the Src and. Syk families, Genetic and biochemical evide nce has shown that the Src family kinases are critical fur normal T cell ma turation, ZAP-70, a Syk family kinase, has similarly been implicated as a c ritical component in thymocyte development. Although genetic evidence has s uggested that Syk is involved during thymocyte development, a definitive st udy of Syk expression has not been performed. In this paper we report our r eanalysis of Syk expression in subpopulations of murine and human thymocyte s by intracellular staining and flow cytometry using anti-Syk mAbs, Syk is expressed at increased levels during the stages in 7 which pre-TCR signalin g occurs, Furthermore, Syk is down-regulated after the pre-TCR checkpoint h as been passed. Syk may play an important role in thymic development during pre-TCR signal transduction, Finally, incomplete down-regulation of Syk ex pression was noted in human thymocytes, offering a possible explanation for the distinct phenotypes of mice and humans deficient in ZAP-70.