TAB2 is essential for prevention of apoptosis in fetal liver but not for interleukin-1 signaling.
The proinflammatory cytokine interleukin-1 (IL-1) transmits a signal via several critical cytoplasmic proteins such as MyD88, IRAKs and TRAF6. Recently, serine/threonine kinase TAK1 and TAK1 binding protein 1 and 2 (TAB1/2) have been identified as molecules involved in IL-1-induced TRAF6-mediated activation of AP-1 and NF-kappa B via mitogen-activated protein (MAP) kinases and I kappa B kinases, respectively. However, their physiological functions remain to be clarified. To elucidate their roles in vivo, we generated TAB2-deficient mice. The TAB2 deficiency was embryonic lethal due to liver degeneration and apoptosis. This phenotype was similar to that of NF-kappa B p65-, IKK beta-, and NEMO/IKK gamma-deficient mice. However, the IL-1-induced activation of NF-kappa B and MAP kinases was not impaired in TAB2-deficient embryonic fibroblasts. These findings demonstrate that TAB2 is essential for embryonic development through prevention of liver apoptosis but not for the IL-1 receptor-mediated signaling pathway.
Sanjo
Hideki
H
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Takeda
Kiyoshi
K
Tsujimura
Tohru
T
Ninomiya-Tsuji
Jun
J
Matsumoto
Kunihiro
K
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005313:Fetal Death / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C099510:TAB1 protein, MAPKKK activator, vertebrate; C498761:Tab2 protein, mouse