Document Detail


JAK2 is an important signal transducer in IL-33-induced NF-κB activation.
MedLine Citation:
PMID:  20940045     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IL-33, a member of the IL-1 family of cytokines, has been shown to activate NF-κB and MAP kinase family through the IL-1 receptor-related protein, ST2L. In this study, we found that IL-33 rapidly activated a tyrosine kinase, JAK2. Interestingly, we demonstrated the functional involvement of JAK2 in IL-33-induced IκBα degradation and NF-κB activation, since a JAK2 inhibitor, AG490, effectively inhibited this signaling pathway. Furthermore, IL-33 failed to induce IκBα degradation and NF-κB activation in JAK2-deficient MEFs expressing ST2L, compared with wild-type MEFs expressing ST2L. In addition, the introduction of wild-type JAK2 but not kinase dead JAK2 mutant (K882R) restored the IL-33-induced efficient activation of NF-κB in JAK2-deficient MEFs expressing ST2L, resulting in the induction of IL-6, CCL2/MCP-1 and CXCL1/KC expression. On the other hand, the activation of ERK, JNK and p38 was unaffected by JAK2 inhibition and JAK2 deficiency. Thus, these data demonstrate that JAK2 plays an important role in regulating IL-33-induced NF-κB activation.
Authors:
Megumi Funakoshi-Tago; Kenji Tago; Yoshinori Sato; Shin-Ichi Tominaga; Tadashi Kasahara
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-19
Journal Detail:
Title:  Cellular signalling     Volume:  23     ISSN:  1873-3913     ISO Abbreviation:  Cell. Signal.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-07     Completed Date:  2011-04-15     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  363-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
Affiliation:
Department of Biochemistry, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan. tago-mg@pha.keio.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Interleukins / physiology*
Janus Kinase 2 / antagonists & inhibitors,  genetics,  physiology*
Macrophages, Peritoneal / drug effects,  metabolism
Male
Mice
Mice, Inbred C57BL
NF-kappa B / biosynthesis*
NIH 3T3 Cells
Signal Transduction
Tyrphostins / pharmacology
Chemical
Reg. No./Substance:
0/Interleukins; 0/NF-kappa B; 0/Tyrphostins; 0/alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; 0/interleukin-33, mouse; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/Jak2 protein, mouse

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