Please use this identifier to cite or link to this item: 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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