| Literature DB >> 11163183 |
C D Dumitru1, J D Ceci, C Tsatsanis, D Kontoyiannis, K Stamatakis, J H Lin, C Patriotis, N A Jenkins, N G Copeland, G Kollias, P N Tsichlis.
Abstract
Tpl2 knockout mice produce low levels of TNF-alpha when exposed to lipopolysaccharide (LPS) and they are resistant to LPS/D-Galactosamine-induced pathology. LPS stimulation of peritoneal macrophages from these mice did not activate MEK1, ERK1, and ERK2 but did activate JNK, p38 MAPK, and NF-kappaB. The block in ERK1 and ERK2 activation was causally linked to the defect in TNF-alpha induction by experiments showing that normal murine macrophages treated with the MEK inhibitor PD98059 exhibit a similar defect. Deletion of the AU-rich motif in the TNF-alpha mRNA minimized the effect of Tpl2 inactivation on the induction of TNF-alpha. Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport of TNF-alpha mRNA from the nucleus to the cytoplasm.Entities:
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Year: 2000 PMID： 11163183 DOI： 10.1016/s0092-8674(00)00210-5
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582