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MAP kinase kinase kinases and innate immunity
Antony Symons1, Soren Beinke, Steven C Ley
1Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Trends in Immunology
|December 17, 2005
Summary
Toll-like receptors and cytokine receptors initiate innate immunity by activating mitogen-activated protein (MAP) kinases. This review details MAP kinase kinase kinases (MAP 3-kinases) that link these receptors to MAP kinases, regulating immune responses.
Area of Science:
- Immunology
- Cell Signaling
- Molecular Biology
Background:
- Innate immune responses are initiated and regulated by Toll-like receptors (TLRs) and receptors for pro-inflammatory cytokines like tumor necrosis factor (TNF) and interleukin-1 (IL-1).
- These receptors activate major mitogen-activated protein (MAP) kinase pathways: extracellular signal-regulated kinases (ERK), c-Jun amino-terminal kinases (JNK), and p38 MAP kinase.
- MAP kinases are critical for cell survival and regulating the expression of immune mediators.
Purpose of the Study:
- To review recent studies on MAP kinase kinase kinases (MAP 3-kinases) that connect innate immune receptors to MAP kinase signaling.
- To elucidate the mechanisms by which innate immune receptors regulate MAP 3-kinase activity.
Main Methods:
- Literature review of recent studies.
- Analysis of signaling pathways linking receptors to MAP 3-kinases.
- Discussion of regulatory mechanisms.
Main Results:
- Identification of specific MAP 3-kinases involved in innate immunity signaling.
- Characterization of how TLRs and cytokine receptors activate these MAP 3-kinases.
- Elucidation of regulatory mechanisms controlling MAP 3-kinase activity downstream of these receptors.
Conclusions:
- MAP 3-kinases are key intermediaries in innate immune signaling pathways.
- Understanding MAP 3-kinase regulation by innate immune receptors is crucial for comprehending immune responses.
- This knowledge may inform strategies for modulating innate immunity.