COT1, active

Background Information:

N-terminal 6His-tagged, recombinant, human COT1, amino acids 30-397. COT1 (MAP3K8) is a serine/threonine kinase that is widely expressed in immune and non-immune cells. It is a proto-oncogene and a target for provirus integration. The enzyme has been shown to be involved in the recruitment, differentiation, and activation of inflammatory and immune cells by regulating the production of pro-inflammatory cytokines, chemokines, enzymes, and growth factors. Overexpression/dysregulation of MAP3K8 has been found in a large number of cancers such as skin cancer, prostate cancer, breast cancer, squamous cell carcinoma, ovarian cancer, hepatocellular carcinoma, colorectal cancer, renal carcinoma, glioma and ovarian carcinomas. It has also been shown to be associated with resistance to chemotherapeutic agents in thyroid cancer and melanoma. Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory 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.

Target Class:

Kinase

Family:

STE

Sub Family:

Serine/threonine kinase

Protein Name:

COT

Accession Number:

Z14138.1

UniProt Number:

P41279

Gene Name:

MAP3K8

Gene ID:

1326

Gene Aliases:

Tpl-2|EST|c-COT|MEKK8

Target Species:

Human