Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blotting, Western
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Enzyme Activation
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Fibroblasts / metabolism
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Humans
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Interleukin-1 / metabolism
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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MAP Kinase Signaling System
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Mice
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Mice, Transgenic
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism
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Plasmids / metabolism
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / metabolism
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Proteins / physiology*
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Receptor-Interacting Protein Serine-Threonine Kinases
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Transfection
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Tumor Necrosis Factor-alpha / metabolism*
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p38 Mitogen-Activated Protein Kinases
Substances
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Interleukin-1
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NF-kappa B
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Proteins
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Tumor Necrosis Factor-alpha
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RIPK1 protein, human
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Receptor-Interacting Protein Serine-Threonine Kinases
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Ripk1 protein, mouse
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases