TY - JOUR
T1 - Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression
AU - Iwashima, Makio
AU - Takamatsu, Masako
AU - Yamagishi, Hiroko
AU - Hatanaka, Yasue
AU - Huang, Yi Ying
AU - McGinty, Courtnie
AU - Yamasaki, Sho
AU - Koike, Toru
PY - 2002/4/2
Y1 - 2002/4/2
N2 - 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.
AB - 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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U2 - 10.1073/pnas.082647499
DO - 10.1073/pnas.082647499
M3 - Article
C2 - 11917142
AN - SCOPUS:0037007092
SN - 0027-8424
VL - 99
SP - 4544
EP - 4549
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 7
ER -