Related Experiment Video
Updated: Jul 29, 2026

Real-time Live Imaging of T-cell Signaling Complex Formation
Published on: June 23, 2013
Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and
K Tomita1, K Saijo, S Yamasaki
1Department of Molecular Genetics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8790, Japan.
Abstract:
Jak3 is responsible for growth signals by various cytokines such as interleukin (IL)-2, IL-4, and IL-7 through association with the common gamma chain (gammac) in lymphocytes. We found that T cells from Jak3-deficient mice exhibit impairment of not only cytokine signaling but also early activation signals and that Jak3 is phosphorylated upon T cell receptor (TCR) stimulation. TCR-mediated phosphorylation of Jak3 is independent of IL-2 receptor/gammac but is dependent on Lck and ZAP-70. Jak3 was found to be assembled with the TCR complex, particularly through direct association with CD3zeta via its JH4 region, which is a different region from that for gammac association. These results suggest that Jak3 plays a role not only in cell growth but also in T cell activation and represents cross-talk of a signaling molecule between TCR and growth signals.
Insights
Janus kinase 3 (Jak3) impacts T cell activation and growth signals. This study reveals Jak3
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Janus kinase 3 (Jak3) is crucial for cytokine signaling pathways, particularly those involving the common gamma chain (gammac) in lymphocytes.
- Its role in T cell activation beyond cytokine signaling remains incompletely understood.
Purpose of the Study:
- To investigate the role of Jak3 in T cell receptor (TCR) signaling and activation.
- To elucidate the mechanisms of Jak3 phosphorylation and its association with the TCR complex.
Main Methods:
- Utilized Jak3-deficient mice to assess T cell function.
- Investigated Jak3 phosphorylation upon TCR stimulation.
- Examined Jak3 association with TCR components, including CD3zeta, Lck, and ZAP-70.
Main Results:
- T cells from Jak3-deficient mice showed impaired cytokine signaling and early activation signals.
- Jak3 phosphorylation was induced by TCR stimulation, independent of the IL-2 receptor/gammac pathway.
- Jak3 directly associates with CD3zeta via its JH4 region, distinct from its gammac binding site.
- Jak3 interaction with TCR complex components Lck and ZAP-70 was observed.
Conclusions:
- Jak3 plays a significant role in T cell activation, not solely in cytokine-mediated growth.
- Jak3 acts as a signaling molecule bridging TCR and growth factor signaling pathways.
- These findings reveal novel cross-talk mechanisms in lymphocyte activation.
More Related Videos
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
The JAK-STAT Signaling Pathway
TGF - β Signaling Pathway
cAMP-dependent Protein Kinase Pathways
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...

