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MAP3K8 / TPL2
mitogen-activated protein kinase kinase kinase 8
Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
| Gene Name: | mitogen-activated protein kinase kinase kinase 8 |
| Family/Subfamily: | Protein Kinase , MAP3K |
| Synonyms: | MAP3K8, C-COT, Cancer Osaka thyroid oncogene, COT, Ewing sarcoma transformant, EST, MEKK8, Proto-oncogene c-Cot, TPL2, Tumor progression locus 2, Protein kinase cot, Tpl-2, ESTF |
| Target Sequences: | NM_005204 NP_005195.2 P41279 |
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