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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
Author(s) -
Kim Eunji,
Yoon Ju Y.,
Lee Jongsung,
Jeong Deok,
Park Jae G.,
Hong Yo H.,
Kim Ji H.,
Aravinthan Adithan,
Kim JongHoon,
Cho Jae Y.
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26787
Subject(s) - map kinase kinase kinase , ask1 , mitogen activated protein kinase kinase , microbiology and biotechnology , protein kinase a , map2k7 , mitogen activated protein kinase , janus kinase , c raf , phosphatase , cyclin dependent kinase 9 , kinase , cyclin dependent kinase 2 , biology , phosphorylation
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.