TLR2- and TLR4-dependent activation of STAT1 serine phosphorylation in murine macrophages is protein kinase C-delta-independent.
J Endotoxin Res
; 12(4): 231-40, 2006.
Article
em En
| MEDLINE
| ID: mdl-16953975
ABSTRACT
Engagement of Toll-like receptor (TLR) proteins activates multiple signal transduction pathways. Previous studies demonstrated that TLR2 and TLR4 engagement leads to rapid phosphorylation of the transcription factor STAT1 at serine 727 (Ser-727 STAT1) in murine macrophages. Only TLR4 engagement induced STAT1 phosphorylation at tyrosine 701, although this response was delayed compared with Ser-727 STAT1 phosphorylation. Unlike other cell types, the p38 mitogen-activated protein kinase was necessary, but not sufficient, for TLR-induced phosphorylation of Ser-727 STAT1 in macrophages. We and others had previously shown that Ser-727 STAT1 phosphorylation could be blocked by rottlerin, an inhibitor of protein kinase C-delta (PKC-delta). Here we report that peritoneal exudate macrophages from PKC-delta-deficient mice can be activated through TLR2 and TLR4 to elicit rapid phosphorylation of Ser-727 STAT1, which was blocked by both rottlerin and the p38 inhibitor SB203580, but not by the pan-PKC inhibitor bisindoylmaleamide. Furthermore, both normal and PKC-delta-deficient macrophages secreted comparable amounts of IL-6, IP-10, and RANTES following TLR engagement. In contrast, IFN-gamma-induced STAT1 serine phosphorylation was independent of both PKC-delta and p38. Overall, these studies demonstrate that a PKC-delta-independent signaling pathway downstream of both TLR2 and TLR4 is necessary for Ser-727 STAT1 phosphorylation in primary murine macrophages.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfosserina
/
Macrófagos Peritoneais
/
Proteína Quinase C-delta
/
Fator de Transcrição STAT1
/
Receptor 2 Toll-Like
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Receptor 4 Toll-Like
Limite:
Animals
Idioma:
En
Revista:
J Endotoxin Res
Assunto da revista:
ANGIOLOGIA
/
BACTERIOLOGIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos