Overview:

COT is an oncogene that can activate both the MAP kinase and JNK kinase pathways. COT activates IκB kinases and induces the nuclear production of NF-κB. C-terminal catalytic domain of KSR2 associates with COT and KSR2 can negatively regulates the kinase activity of COT in vitro. Co-transfection of KSR2 with COT in cells leads to reduced COT-mediated ERK activation and COT-induced IL8 production in a dose-dependent manner (1). COT is one of the MAP kinase kinase kinases that regulates the ERK1/ERK2 pathway in response to IL-1. Blockage of expression of COT results in failure of IL-1 to induce an increase in IL-8 and MIP-1betamRNA levels (2).

Gene Aliases:

MAP3K8, EST, ESTF, TPL2, Tpl-2, c-COT, FLJ10486

Genbank Number:

NM_005204

References:

1. Channavajhala, P L. et al: Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling. J. Biol. Chem. 278: 47089-47097, 2003.

2. Rodríguez C. et al: TRAF6 and Src kinase activity regulates Cot activation by IL-1. Cell Signal. 2006 Sep;18(9):1376-85.