Abstract
TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors following TNF stimulation. To investigate the physiological role of TRAF2, we generated TRAF2-deficient mice. traf2-/- mice appeared normal at birth but became progressively runted and died prematurely. Atrophy of the thymus and spleen and depletion of B cell precursors also were observed. Thymocytes and other hematopoietic progenitors were highly sensitive to TNF-induced cell death and serum TNF levels were elevated in these TRAF2-deficient animals. Examination of traf2-/- cells revealed a severe reduction in TNF-mediated JNK/SAPK activation but a mild effect on NF-kappaB activation. These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
-
Cell Death / drug effects*
-
Cycloheximide / pharmacology
-
Enzyme Activation
-
Female
-
Hematopoietic Stem Cells / cytology
-
JNK Mitogen-Activated Protein Kinases
-
Liver / embryology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mitogen-Activated Protein Kinases*
-
NF-kappa B / physiology*
-
Protein Synthesis Inhibitors / pharmacology
-
Proteins / physiology*
-
Receptors, Tumor Necrosis Factor / physiology*
-
Signal Transduction
-
TNF Receptor-Associated Factor 2
-
Tumor Necrosis Factor-alpha / pharmacology*
Substances
-
NF-kappa B
-
Protein Synthesis Inhibitors
-
Proteins
-
Receptors, Tumor Necrosis Factor
-
TNF Receptor-Associated Factor 2
-
Tumor Necrosis Factor-alpha
-
Cycloheximide
-
Calcium-Calmodulin-Dependent Protein Kinases
-
JNK Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinases