Mitogen-activated protein kinases in innate immunity

  title={Mitogen-activated protein kinases in innate immunity},
  author={J. Simon C. Arthur and Steven C. Ley},
  journal={Nature Reviews Immunology},
  • J. Arthur, S. Ley
  • Published 1 September 2013
  • Biology, Medicine
  • Nature Reviews Immunology
Following pathogen infection or tissue damage, the stimulation of pattern recognition receptors on the cell surface and in the cytoplasm of innate immune cells activates members of each of the major mitogen-activated protein kinase (MAPK) subfamilies — the extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal kinase (JNK) subfamilies. In conjunction with the activation of nuclear factor-κB and interferon-regulatory factor transcription factors, MAPK activation induces the… 
The Expanding Role of p38 Mitogen-Activated Protein Kinase in Programmed Host Cell Death
There is evidence demonstrating that p38 MAPK is a potent trigger of pathogen-induced necrosis driven by mitochondrial membrane disruption and this findings provide an opportunity to repurpose these drugs for improved control of infectious diseases.
Extracellular signal–regulated kinase 5 promotes acute cellular and systemic inflammation
A proinflammatory role for ERK5 is found in primary human endothelial cells and monocytes, and inhibitors of ERk5 and its upstream activating kinase MEK5 reduced systemic inflammation in various mouse models of microbial infection and noninfectious tissue injury, raising the possibility that ERK 5 might have therapeutic potential for the treatment of inflammatory disorders.
MAP Kinase Modules in Signaling
Compromised MAPK signaling in human diseases: an update
Recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions is summarized.
Microbial Degradation of Cellular Kinases Impairs Innate Immune Signaling and Paracrine TNFα Responses
A novel mechanism by which the opportunistic pathogen Porphyromonas gingivalis dampens innate immune responses by disruption of kinase signaling and degradation of inflammatory mediators is identified.
Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases.
Current and emerging new information indicate that developing MK2 inhibitors and blocking MK2-mediated signal pathways are potential therapeutic strategies for treatment of inflammatory and fibrotic lung diseases and lung cancer.
Subverting Toll-Like Receptor Signaling by Bacterial Pathogens
This mini-review highlights the diverse mechanisms that bacterial pathogens have evolved to manipulate the innate immune response, with a particular focus on those that target MAPK and NF-κB signaling pathways.
The IκB-protein BCL-3 controls Toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus
The surprising discovery that active TPL-2 shuttles between the cytoplasm and the nucleus, where it is degraded by the proteasome is reported, indicating the nucleus is a key site in the regulation of TLR-induced MAPK activity.


Regulation of the immune response by stress‐activated protein kinases
What is currently known about the role of two sub‐groups of SAPKs – c‐Jun NH2‐terminal kinase and p38 MAPK‐in the function of specific components of the immune system and the overall contribution to the immune response is summarized.
Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
PAC-1 is a key positive regulator of inflammatory cell signaling and effector functions, mediated through Jnk and Erk mitogen-activated protein kinase crosstalk.
Signaling in innate immunity and inflammation.
Although the role of inflammation is to resolve infection and injury, increasing evidence indicates that chronic inflammation is a risk factor for cancer.
Targeting of TAK1 in inflammatory disorders and cancer.
  • H. Sakurai
  • Biology
    Trends in pharmacological sciences
  • 2012
Mitogen-Activated Protein Kinase Phosphatase 2 Regulates the Inflammatory Response in Sepsis
Data support a mechanism by which MKP-2 targets ERK deactivation, thereby decreasingMKP-1 and thus removing the negative inhibition of MKp-1 on cytokine production, which is needed for sepsis to be eliminated.
Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5
MKP5 has a principal function in both innate and adaptive immune responses, and represents a novel target for therapeutic intervention of immune diseases.
Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases
The mechanisms of MAPKAPK activation by the different MAPKs are reviewed and their physiological roles based on established substrates and recent discoveries are discussed.
Acetylation of MEK2 and IκB kinase (IKK) activation loop residues by YopJ inhibits signaling
The results establish a hitherto uncharacterized mode of action for bacterial toxins and suggest the possibility that serine/threonine acetylation may occur even under nonpathogenic conditions and may be a widespread protein modification regulating protein function in eukaryotic cells.
Macrophage signalling upon mycobacterial infection: the MAP kinases lead the way
Mycobacteria activate a series of macrophage signalling pathways upon engaging host cell receptors and during the invasion process. These signals initiate a cascade of events leading to the