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Proceedings of the National Academy of Sciences
Article . 2004 . Peer-reviewed
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Activation of naïve CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling

Authors: Katsuji, Sugie; Myung-Shin, Jeon; Howard M, Grey;

Activation of naïve CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling

Abstract

Although there was no impairment in IL-2 secretion and proliferation of Fyn-deficient naïve CD4 cells after stimulation with antigen and antigen-presenting cells, stimulation of these cells with anti-CD3 and anti-CD28 revealed profound defects. Crosslinking of purified wild-type naïve CD4 cells with anti-CD3 activated Lck and initiated the signaling cascade downstream of Lck, including phosphorylation of ZAP-70, LAT, and PLC-γ1; calcium flux; and dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT)p. All of these signaling events were diminished severely in Fyn-deficient naïve cells activated by CD3 crosslinking. Coaggregation of CD3 and CD4 reconstituted this Lck-dependent signaling pathway in Fyn -/- T cells. These results suggest that when signaling of naïve T cells is restricted to the T cell antigen receptor, Fyn plays an essential role by positive regulation of Lck activity.

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Keywords

CD4-Positive T-Lymphocytes, Mice, Knockout, CD3 Complex, Cell Culture Techniques, Receptors, Antigen, T-Cell, Mice, Transgenic, Lymphocyte Activation, Transcription Factor AP-1, Mice, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Animals, Interleukin-2, Calcium, Lymph Nodes, Phosphorylation, Spleen, Adaptor Proteins, Signal Transducing

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    53
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
53
Top 10%
Top 10%
Top 10%
bronze