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Tyrosine kinase Syk associates with toll‐like receptor 4 and regulates signaling in human monocytic cells
Author(s) -
Chaudhary Anu,
Fresquez Theresa M,
Naranjo Michele J
Publication year - 2007
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/sj.icb7100030
Subject(s) - syk , receptor tyrosine kinase , microbiology and biotechnology , tyrosine kinase , toll like receptor , ror1 , receptor , cancer research , thp1 cell line , signal transduction , chemistry , biology , platelet derived growth factor receptor , cell culture , biochemistry , innate immune system , genetics , growth factor
Toll‐like receptor 4 (TLR4) induces an innate immune response in mammals by recognizing lipopolysaccharide (LPS), a component of the cell wall of Gram‐negative bacteria. In this study, we show that tyrosine kinase Syk constitutively associates with TLR4 in THP‐1 cells. As previously reported in peripheral blood mononuclear cells, TLR4 gets inducibly tyrosine phosphorylated upon LPS engagement in THP‐1 cells. Piceatannol, a pharmacological inhibitor of the tyrosine kinase Syk, abrogates TLR4 tyrosine phosphorylation at low doses. The kinetics of TLR4 tyrosine phosphorylation in THP‐1 cells coincides with an early wave of Syk tyrosine phosphorylation. Additionally, serine threonine kinase interleukin‐1 (IL1) receptor‐associated kinase 1 (IRAK‐1) is transiently recruited to the complex containing adaptor molecule MyD88, TLR4 and Syk within 1 min of LPS engagement and dissociates by 30 min. Finally, the inhibition of Syk with piceatannol has no effect on LPS‐mediated release of cytokines IL6, IL1 β , tumor necrosis factor‐ α , neither on chemokines macrophage inhibitory protein (MIP)1 α , MIP1 β , monocyte chemoattractant protein ‐1, IL8, Gro α and RANTES. However, IL10 and IL12p40 releases are significantly inhibited. Our findings implicate Syk as a novel modulator of LPS‐mediated TLR4 responses in human monocytic cells and shed insight into the kinetics of early complex formation upon LPS engagement.