TANK‐binding kinase 1 and Janus kinase 2 play important roles in the regulation of mitogen‐activated protein kinase phosphatase‐1 expression after toll‐like receptor 4 activation. Issue 11 (24th May 2018)

• Record Type: Journal Article
• Authors: Kim, Eunji; Yoon, Ju Y.; Lee, Jongsung; Jeong, Deok; Park, Jae G.; Hong, Yo H.; Kim, Ji H.; Aravinthan, Adithan; Kim, Jong‐Hoon; Cho, Jae Y.
• Is Part Of: Journal of cellular physiology. Volume 233:Issue 11(2018:Nov.)
• Page Start: 8790
• Page End: 8801
• Publication Date: 2018-05-24
• Subjects: inflammatory signaling -- JAK2 -- MKP1 -- STAT3 -- TBK1 -- TLR4; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26787
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Inflammation is a response that protects the body from pathogens. Through several inflammatory signaling pathways mediated by various families of transcription factors, such as nuclear factor‐κB (NF‐κB), activator protein‐1 (AP‐1), interferon regulatory factors (IRFs), and signal transducers and activators of transcription (STATs), various inflammatory cytokines and chemokines are induced and inflammatory responses are boosted. Simultaneously, inhibitory systems are activated and provide negative feedback. A typical mechanism by which this process occurs is that inflammatory signaling molecules upregulate mitogen‐activated protein kinase phosphatase‐1 (MKP1) expression. Here, we investigated how kinases regulate MKP1 expression in lipopolysaccharide‐triggered cascades. We found that p38 and c‐Jun N‐terminal kinase (JNK) inhibitors decreased MKP1 expression. Using specific inhibitors, gene knockouts, and gene knockdowns, we also found that tumor necrosis factor receptor‐associated factor family member‐associated nuclear factor κB activator (TANK)‐binding kinase 1 (TBK1) and Janus kinase 2 (JAK2) are involved in the induction of MKP1 expression. By analyzing JAK2‐induced activation of STATs, STAT3‐specific inhibitors, promoter binding sites, and STAT3 −/− cells, we found that STAT3 is directly linked to TBK1‐mediated and JAK2‐mediated induction of MKP1 expression. Our data suggest that MKP1 expression can be differentially regulated by p38, JNK, and the TBK1–JAK2–STAT3 pathway after activation of toll‐like receptor 4 (TLR4). These data also imply crosstalk between the AP‐1 pathway and the IRF3 and STAT3 pathways. Abstract : (1) p38 and c‐Jun N‐terminal kinase inhibitors decreased MKP1 expression. (2) TBK1 and Janus kinase 2 (JAK2) are involved in the induction of MKP1 expression. (3) Signal transducer and activator of transcription 3 is directly linked to TBK1‐mediated and JAK2‐mediated induction of MKP1 expression.