Genetic evidence for Shc requirement in TCR-induced c-Rel nuclear translocation and IL-2 expression.
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.
Iwashima
Makio
M
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912-2600, USA. makio@immag.mcg.edu
Takamatsu
Masako
M
Yamagishi
Hiroko
H
Hatanaka
Yasue
Y
Huang
Yi-Ying
YY
McGinty
Courtnie
C
Yamasaki
Sho
S
Koike
Toru
T
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D019169:Jurkat Cells; D037181:Lectins, C-Type; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099192:CD69 Antigens
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D037181:Lectins, C-Type; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011506:Proteins; D020569:Proto-Oncogene Proteins c-rel; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000099192:CD69 Antigens; C528024:SHC1 protein, human