Tp12 kinase signal transduction in inflammation and cancer

The activation of mitogen-activated protein kinases (MAPKs) is critically involved in inflammatory and oncogenic events. Tumor progression locus 2 (Tp12), also known as COT and MAP3 kinase 8 (MAP3K8), is a serine-threonine kinase with an important physiological role in tumor necrosis factor, interleukin-1, CD40, Toll-like receptor and G protein-coupled receptor-mediated ERK MAPK signaling. Whilst the full characterization of the biochemical events that lead to the activation of Tp12 still represent a major challenge, genetic and molecular evidence has highlighted interesting interactions with the NF-kappa B network. Here, we provide an overview of the multifaceted functions of Tp12 and the molecular mechanisms that govern its regulation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.