Abstract
Tpl2 knockout mice produce low levels of TNF-α 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-κB. The block in ERK1 and ERK2 activation was causally linked to the defect in TNF-α 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-α mRNA minimized the effect of Tpl2 inactivation on the induction of TNF-α. Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport, of TNF-α mRNA from the nucleus to the cytoplasm.
Original language | English (US) |
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Pages (from-to) | 1071-1083 |
Number of pages | 13 |
Journal | Cell |
Volume | 103 |
Issue number | 7 |
DOIs | |
State | Published - Dec 22 2000 |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)