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T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation
J B Crawley1, L Rawlinson, F V Lali
1The Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London W6 8LH, United Kingdom.
Abstract:
Interleukin-2 (IL-2) is a potent T cell mitogen. However, the signaling pathways by which IL-2 mediates its mitogenic effect are not fully understood. One of the members of the mitogen-activated protein kinase (MAPK) family, p42/44MAPK (ERK2/1), is known to be activated by IL-2. We have now investigated the response to IL-2 of two other members of the MAP kinase family, p54MAP kinase (stress-activated protein kinase (SAPK)/Jun-N-terminal kinase (JNK)) and p38MAP kinase (p38/Mpk2/CSBP/RK), which respond primarily to stressful and inflammatory stimuli (e.g. tumor necrosis factor-alpha, IL-1, and lipopolysaccharide). Here we show that IL-2, and another T cell growth factor, IL-7, activate both SAPK/JNK and p38MAP kinase. Furthermore, inhibition of p38MAP kinase activity with a specific pyrinidyl imidazole inhibitor SB203580 that prevents activation of its downstream effector, MAPK-activating protein kinase-2, correlated with suppression of IL-2- and IL-7-driven T cell proliferation. These data indicate that in T cells p38MAP kinase has a role in transducing the mitogenic signal.
Insights
Interleukin-2 (IL-2) activates stress-related MAP kinases, including p38MAP kinase, in T cells. Inhibiting p38MAP kinase suppresses IL-2-driven T cell proliferation, revealing its role in T cell growth.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Interleukin-2 (IL-2) is a key T cell mitogen, but its precise signaling pathways remain unclear.
- While p42/44MAPK (ERK2/1) activation by IL-2 is known, the roles of other MAP kinases are less understood.
Purpose of the Study:
- To investigate the activation of p54MAP kinase (SAPK/JNK) and p38MAP kinase by IL-2 in T cells.
- To determine the role of p38MAP kinase in IL-2-mediated T cell proliferation.
Main Methods:
- Activation of SAPK/JNK and p38MAP kinase by IL-2 and IL-7 was assessed.
- The effect of p38MAP kinase inhibition using SB203580 on T cell proliferation was evaluated.
Main Results:
- IL-2 and IL-7 were found to activate both SAPK/JNK and p38MAP kinase in T cells.
- Inhibition of p38MAP kinase activity suppressed IL-2- and IL-7-driven T cell proliferation.
Conclusions:
- p38MAP kinase is activated by IL-2 and IL-7 in T cells.
- p38MAP kinase plays a significant role in mediating the mitogenic effects of IL-2 and IL-7 on T cell proliferation.