TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival.
TRAF2 is believed to mediate the activation of NF-kappaB and JNK induced by the tumor necrosis factor receptor (TNFR) superfamily, which elicits pleiotropic responses in lymphocytes. We have investigated the physiological roles of TRAF2 in these processes by expressing a lymphocyte-specific dominant negative form of TRAF2, thereby blocking this protein's effector function. We find that the TNFR superfamily signals require TRAF2 for activation of JNK but not NF-kappaB. In addition, we show that TRAF2 induces NF-kappaB-independent antiapoptotic pathways during TNF-induced apoptosis. Inhibition of TRAF2 leads to splenomegaly, lymphadenopathy, and an increased number of B cells. These findings indicate that TRAF2 is involved in the regulation of lymphocyte function and growth in vivo.
Lee
S Y
SY
Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.
Reichlin
A
A
Santana
A
A
Sokol
K A
KA
Nussenzweig
M C
MC
Choi
Y
Y
D000818:Animals; D019013:CD40 Antigens / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002470:Cell Survival; D004789:Enzyme Activation; D006984:Hypertrophy; D048031:JNK Mitogen-Activated Protein Kinases; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction; D013163:Splenomegaly; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019013:CD40 Antigens; D016328:NF-kappa B; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases