The role of the death-domain kinase RIP in tumour-necrosis-factor-induced activation of mitogen-activated protein kinases.
The death-domain kinase RIP (receptor-interacting protein) is an important effector of tumour necrosis factor (TNF) signalling and is essential for TNF-induced nuclear factor-kappaB activation. However, the function of RIP in the TNF-induced activation of mitogen-activated protein kinases (MAPKs) has not been fully investigated. In this report, using Rip null (Rip(-/-)) mouse fibroblast cells, we investigated whether RIP is required for TNF-induced activation of the MAPKs extracellular-signal-related kinase (ERK), p38 and c-Jun amino-terminal kinase (JNK). We found that TNF-induced activation of ERK, p38 and JNK is decreased in Rip(-/-) cells. The activation of these kinases by interleukin-1 is normal in Rip(-/-) cells. More importantly, we showed that the kinase activity of RIP is needed for ERK activation.
Devin
Anne
A
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Lin
Yong
Y
Liu
Zheng-gang
ZG
D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D007375:Interleukin-1; D016328:NF-kappa B; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases