Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression

Proceedings of the National Academy of Sciences of the United States of America
Makio IwashimaToru Koike

Abstract

Shc, a prototypic adapter molecule, has been implicated in T cell receptor (TCR) signal transduction, but its role has not been identified clearly. Here we report that Shc is essential for TCR-induced IL-2 production but is dispensable for CD69 or CD25 expression. Engagement of TCR in mutant Jurkat T cells lacking Shc fails to produce IL-2 because of impaired mitogen-activated protein kinase activation. Activation of c-Rel, a transcription factor essential for IL-2 expression, was impaired also. In contrast, activation of nuclear factor of activated T cell and expression of CD69/CD25 were comparable between the mutant and wild-type Jurkat cells. These defects were rescued by expression of exogenous Shc. Activation of c-Rel using the estrogen receptor fusion protein restored the activation of the IL-2 promoter in an estrogen-dependent manner. These results show that Shc plays an essential role in the TCR-induced activation of c-Rel and the IL-2 promoter.

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Citations

Jun 6, 2003·Current Opinion in Immunology·Erin Janssen, Weiguo Zhang
Nov 3, 2009·International Immunology·Jing-Wen ChangMakio Iwashima
Jan 30, 2004·Molecular and Cellular Biology·Sonia PaciniCosima T Baldari
Jun 1, 2007·Blood·Laura PatrussiCosima T Baldari
Apr 3, 2003·Immunological Reviews·Lawrence P Kane, Arthur Weiss
Nov 17, 2009·Immunological Reviews·Francesca FinettiCosima T Baldari
Feb 21, 2009·Journal of Molecular Recognition : JMR·Tao LiuShaojun Liu
May 12, 2004·Current Opinion in Immunology·Luca SimeoniBurkhart Schraven
Mar 5, 2003·Immunological Reviews·Li ZhangKodi S Ravichandran
Apr 16, 2004·The Journal of Biological Chemistry·Yanping Huang, Ronald L Wange
Dec 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M Lienhard SchmitzOliver Dienz
Nov 1, 2005·Cellular Signalling·Atsuki FukushimaMakio Iwashima

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