title: Pre-T cell receptor signals are responsible for the down-regulation of Syk protein tyrosine kinase expression.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Chu
authors.forename: N S
authors.initials: NS
authors.lastname: van Oers
authors.forename: M
authors.initials: M
authors.lastname: Malissen
authors.forename: J
authors.initials: J
authors.lastname: Harris
authors.forename: M
authors.initials: M
authors.lastname: Elder
authors.forename: A
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007424:Intracellular Fluid / Q000201:enzymology; D047908:Intracellular Signaling Peptides and Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013194:Staining and Labeling; D000072377:Syk Kinase; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D004792:Enzyme Precursors; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse