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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/33447

Title: Bruton's tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NF-kappa B activation by LPS
Author: DOYLE, SARAH LOUISE
O'NEILL, LUKE ANTHONY JOHN
Author's Homepage: http://people.tcd.ie/laoneill
http://people.tcd.ie/doyles8
Keywords: Biochemistry
Issue Date: 2005
Citation: Doyle S, Jefferies CA and O Neill LA, Bruton's tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NF-kappa B activation by LPS, J Biol Chem., 280, 25, 2005, 23496, 23501
Series/Report no.: J Biol Chem.
280
25
Abstract: Bruton's tyrosine kinase (Btk) has recently been shown to participate in the induction of nuclear factor κB (NFκB)-dependent gene expression by the lipopolysaccharide (LPS) receptor Toll-like receptor-4 (TLR4). In this study we have examined the mechanism whereby Btk participates in this response. Treatment of the murine monocytic cell line Raw264.7 with LFM-A13, a specific Btk inhibitor, blocked LPS-induced NFκB-dependent reporter gene expression but not IκBα degradation. Transient transfection of HEK293 cells with Btk had no effect on NFκB-dependent reporter gene expression but strongly promoted transactivation of a reporter gene by a p65-Gal4 fusion protein. IκBα degradation activated by LPS was intact in macrophages from X-linked immunodeficiency (Xid) mice, which contain inactive Btk. Transfection of cells with a dominant negative form of Btk (BtkK430R) inhibited LPS-driven p65 mediated transactivation. Additionally LFM-A13 impaired phosphorylation of serine 536 on p65 induced by LPS in HEK293-TLR4 cells, and in Xid macrophages this response was impaired. This study therefore reveals a novel function for Btk. It is required for the signaling pathway activated by TLR4, which culminates in phosphorylation of p65 on serine 536 promoting transactivation by NFκB.
Description: PUBLISHED
PMID: 15849198
URI: http://dx.doi.org/10.1074/jbc.C500053200
http://hdl.handle.net/2262/33447
Related links: http://www.jbc.org/cgi/reprint/280/25/23496
Appears in Collections:Biochemistry (Scholarly Publications)

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