MAP3K8
MAP3K8 (mitogen-activated protein kinase kinase kinase 8, also known as Tpl-2, COT, c-COT, MEKK8, EST and ESTF) is a cytoplasmic serine/threonine protein kinase. It links inflammatory and immune receptor signals to the MAPK/ERK pathway and controls production of cytokines such as TNF. Browse Assay Genie's current range of MAP3K8 research reagents below, or read on for the biology behind the target.
MAP3K8 is a serine/threonine kinase that sits upstream in mitogen-activated protein kinase signalling. It is required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, and is therefore critical for production of the pro-inflammatory cytokine TNF during immune responses. It also transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and may contribute to the regulation of immunoglobulin production. In some cell types it may also take part in TNF signals that activate JNK and NF-kappa-B, and it has been shown to activate IkappaB kinases.
Beyond macrophage signalling, MAP3K8 is involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells, and promotes TNF-alpha and IL-2 production during T lymphocyte activation. It helps mediate host resistance to bacterial infection through negative regulation of type I interferon production. In vitro, it activates the MAPK/ERK pathway in response to IL1 independently of IRAK1, leading to up-regulation of IL8 and CCL4. In adipocytes, it acts in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, to induce lipolysis. It also plays a role in the cell cycle.
The MAP3K8 gene is classed as an oncogene and the protein belongs to the STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily. The gene can use a downstream in-frame translation start codon, producing an isoform with a shorter N-terminus that shows weaker transforming activity than the longer form. Mouse and rat orthologs are both named Map3k8.
MAP3K8 is required for TLR4-mediated ERK activation and TNF production in LPS-stimulated macrophages, making it a central node in inflammatory responses.
It contributes to T-helper differentiation, IFNG expression and IL-2 production in T-cells, and transduces CD40 signals in B-cells.
MAP3K8 supports resistance to bacterial infection through negative regulation of type I interferon production.
As an oncogene with transforming activity in its longer isoform, MAP3K8 is studied in MAPK, JNK and NF-kappaB signalling.
MAP3K8 is a cytoplasmic serine/threonine kinase that activates the MAPK/ERK pathway downstream of TLR4, IL1, CD40 and TNFRSF1A. It is required for LPS-induced TNF production in macrophages and helps regulate T-cell differentiation, IFNG expression and, in adipocytes, lipolysis.
MAP3K8 is also called Tpl-2, COT, c-COT, MEKK8, EST and ESTF. Its full name is mitogen-activated protein kinase kinase kinase 8. Two forms exist: a longer isoform and a shorter N-terminal isoform from a downstream in-frame start codon, which has weaker transforming activity.
Mouse and rat both carry a Map3k8 ortholog. MAP3K8 is classed as an oncogene, and its longer isoform shows some transforming activity, though much weaker than the activated oncogenic variant. Check the datasheet of any product for its validated reactivity.
Other MAP kinase kinase kinases and downstream MAP2K kinases in ERK, JNK and NF-kappaB signalling, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P41279; product specifications from Assay Genie datasheets.