A nonredundant role for the adapter protein Shc in thymic T cell development
- 8 July 2002
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 3 (8) , 749-755
- https://doi.org/10.1038/ni820
Abstract
Signaling via the pre-T cell receptor (pre-TCR) regulates survival, proliferation, allelic exclusion and differentiation of thymocytes. The role played by the adapter protein Shc in T cells has remained controversial, and its role in pre-TCR signaling has not been addressed. We examined Shc function in thymic T cell development using two genetic approaches. Cre-loxP–mediated inducible expression in transgenic mice of a phosphorylation-defective mutant of Shc impaired signaling through the pre-TCR as well as subsequent proliferation and differentiation. Conditional deletion of the Shc locus in thymocytes also affected thymic maturation at the same pre-TCR developmental stage. Thus, both Shc expression and its tyrosine phosphorylation play an essential and nonredundant role in thymic T cell development.Keywords
This publication has 38 references indexed in Scilit:
- Transgenic analysis of thymocyte signal transductionNature Reviews Immunology, 2002
- Constitutive activation of the Ras/MAP kinase pathway and enhanced TCR signaling by targeting the Shc adaptor to membrane raftsOncogene, 2000
- The role of membrane-associated adaptors in T cell receptor signallingSeminars in Immunology, 2000
- The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein–protein interactionsCurrent Biology, 1996
- Inducible Gene Targeting in MiceScience, 1995
- Interaction of Shc with Grb2 Regulates the Grb2 Association with mSOSAnnals of the New York Academy of Sciences, 1995
- CD3ε-mediated signals rescue the development of CD4+CD8+ thymocytes in RAG-2−/− mice in the absence of TCR β chain expressionInternational Immunology, 1994
- The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1Nature, 1993
- Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinasesNature, 1992
- A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transductionCell, 1992