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http://bura.brunel.ac.uk/handle/2438/8586
Title: | Cytokine-induced Src homology 2 protein (CIS) promotes T cell receptor-mediated proliferation and prolongs survival of activated T cells |
Authors: | Chen, S Xu, X Sundstedt, A Paulsson, KM Anderson, P Karlsson, S Sjögren, HO Wang, P |
Keywords: | Cytokine-induced SH2 protein;T cell receptor;Signal transduction;Mitogen-activated protein kinases;T cell activation |
Issue Date: | 2000 |
Publisher: | The Rockefeller University Press |
Citation: | Journal of Experimental Medicine, 191(6), 985 - 994, 2000 |
Abstract: | Members of the suppressor of cytokine signaling (SOCS) family were discovered as negative regulators of cytokine signaling by inhibition of the Janus kinase–signal transducer and activator of transcription (Jak-STAT) pathway. Among them, cytokine-induced Src homology 2 (SH2) protein (CIS) was found to inhibit the interleukin 3– and erythropietin-mediated STAT5 signaling pathway. However, involvement of SOCS proteins in other signaling pathways is still unknown. This study shows that the expression of CIS is selectively induced in T cells after T cell receptor (TCR) stimulation. In transgenic mice, with selective expression of CIS in CD4 T cells, elevated CIS strongly promotes TCR-mediated proliferation and cytokine production in vitro, and superantigen-induced T cell activation in vivo. Forced expression of CIS also prolongs survival of CD4 T cells after TCR activation. Molecular events immediately downstream from the TCR are not changed in CIS-expressing CD4 T cells, but activation of mitogen-activated protein (MAP) kinase pathways by TCR stimulation is significantly enhanced. Together with the increased MAP kinase activation, a direct interaction of CIS and protein kinase Cθ was also demonstrated. These results suggest that CIS is one of the important regulators of TCR-mediated T cell activation. The functions of CIS, enhancing TCR signaling and inhibiting cytokine signaling, may be important in the regulation of immune response and homeostasis. |
Description: | Copyright @ 2000 The Rockefeller University Press. This article is shared under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode. |
URI: | http://jem.rupress.org/content/191/6/985.abstract http://bura.brunel.ac.uk/handle/2438/8586 |
DOI: | http://dx.doi.org/10.1084/jem.191.6.985 |
ISSN: | 0022-1007 |
Appears in Collections: | Biological Sciences Publications Dept of Life Sciences Research Papers |
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