J Bacteriol Virol.  2012 Sep;42(3):189-195. 10.4167/jbv.2012.42.3.189.

Mitogen-activated Protein Kinases in Inflammation

• Manzoor Z
• Koh YS

• KMID: 1434747
• DOI: http://doi.org/10.4167/jbv.2012.42.3.189

Abstract

Mitogen-activated protein kinases (MAPKs) play critical regulatory roles in the production of the pro-inflammatory cytokines and downstream signaling events which lead to inflammation. Inflammation is a primarily localized and protective response of host against microbial infection. Controlled inflammation is beneficial and necessary for host defense while uncontrolled inflammatory response results in inflammatory diseases such as septic shock, rheumatoid arthritis and cancer. The MAPK family consists of three subfamilies; the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases (JNKs), and the p38 MAPKs. MAPKs are involved in transmitting extracellular signals to nucleus which leads to gene regulation. In this review, we summarize the current knowledge of ERK1/2, JNKs, and p38 MAPK members and their roles in inflammation.

Keyword

MAPKs; Inflammation

MeSH Terms

Arthritis, Rheumatoid
Cytokines
Extracellular Signal-Regulated MAP Kinases
Humans
Inflammation
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Shock, Septic
Cytokines
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinases
Phosphotransferases
p38 Mitogen-Activated Protein Kinases

Figure

• 

  Figure 1 MAPK signaling pathways. The MAPK signaling pathway is stimulated by stress, growth factors, pathogen-associated molecular patterns and inflammatory cytokines. Stimulation of MAPKKK (A-Raf, B-Raf, and C-Raf) leads to the phosphorylation and activation of a MAPKK (MEK1/2) which then stimulates MAPK (ERK1/2) activity. Activation of ASK1, TAK1, and MEKK1/2 by stimuli results in activation of MEK4/7 which are responsible for the activation of JNKs. The phosphorylation of p38 is managed by MKK3/6 which are under upstream control of MTK1 and ASK1. Activation of TAK1 subsequently induces activation and translocation of NF-κB to nucleus. ERK1/2, JNK, and p38 are responsible for activation of transcription factors including TCF/ELK1, ATF-2 and AP-1, and others. Various transcription factors including these lead to expression of genes encoding inflammatory cytokines, cell differentiation, growth and apoptosis. TFs, transcription factors; GF, growth factor; GFR, growth factor receptor; TLR, Toll-like receptor; PAMPs, pathogen-associated molecular patterns; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor.

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