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Role of JAK2–STAT3 in TLR2‐mediated tissue factor expression
Author(s) -
Park DaeWeon,
Lyu Ji Hyo,
Kim JinSik,
Chin Haemin,
Bae YoeSik,
Baek SukHwan
Publication year - 2013
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24472
Subject(s) - phosphorylation , chemistry , microbiology and biotechnology , tissue factor , stat3 , biology , medicine , coagulation
Tissue factor (TF) is a core protein with an essential function in the coagulation cascade that maintains the homeostasis of the blood vessels. TF not only participates in neointima formation, but also causes the development of atherosclerosis. This study investigated the mechanism regulating TF expression in macrophages using Pam 3 CSK 4 , a TLR2 ligand. Pam 3 CSK 4 induced TF expression in two types of macrophages (Raw264.7 and BMDM), but not in TLR2 KO mice derived BMDM. Pam 3 CSK 4 induced TF expression was inhibited by pretreatment with pan‐JAK inhibitor or JAK2 inhibitor AG490. JAK2 knock‐down by siRNA inhibited Pam 3 CSK 4 induced TF expression. Pam 3 CSK 4 stimulated STAT3 phosphorylation (S727), while STAT3 knock‐down by siRNA reduced Pam 3 CSK 4 induced TF expression. These results suggest that Pam 3 CSK 4 induced TF expression is regulated by the JAK2–STAT3 signaling pathway. Pam 3 CSK 4 , unlike increased TF expression, significantly decreased RGS2 expression, while RGS2 overexpression decreased Pam 3 CSK 4 induced TF expression. Inhibition of TF by RGS2 WT did not occur in mutants with flawed RGS domains. We also investigated the correlation between RGS2 and STAT3 phosphorylation. RGS2 knock‐down elevated Pam 3 CSK 4 induced STAT3 phosphorylation, but RGS2 overexpression had the opposite effect on STAT3 phosphorylation. These results suggest that, while Pam 3 CSK 4 induced TF expression is regulated by JAK2–STAT3 signaling, RGS2 is a negative regulator targeted to STAT3. J. Cell. Biochem. 114: 1315–1321, 2013. © 2012 Wiley Periodicals, Inc.