Tumor progression locus 2

Accession # AAI13567 and Alternate Nomenclature: c-COT; COT; EST; ESTF; FLJ10486; ; , MEKKK8, Tumor progression locus 2 (Tpl2),Cot/MAP3K8

Tumor progression locus 2 (Tpl2) is a hematopoietically expressed serine-threonine protein kinase critical in innate immunity linking TOLL receptor (TLRs) to TNF production via activation of its extracellular signal regulated kinase (ERK) kinase (1).  MAP3K8 is shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation.  Gram positive bacterial infection like Listeria monocytogenes is capable of activating both TLRs and non TLR particle recognition receptors (PRRs) and cause MAP3K8 dependent production of TNF, IFN and IL2 (2).  MAP3K8 activation also promotes Androgen depletion-independent prostate cancer growth (3). MAP3K8 is selectively involved in inflammatory cytokine-induced ERK1/2 activation in adipocytes and is implicated in dysfunction of adipose tissue in obesity (4). 

MAP3K8 was identified as a signaling molecule that is required for the regulation of critical function of T helper cells in promoting expression of transcription factors that derived optimal Th1 differentiation (5). MAP3K8 is expressed in immune cells whilst, over expression of MAP3K8 in PBMC causes dys-regulation og IFN-Y, STS4, IL-12 and many other cytokines (6). MAP3K8 gene is located on chromosome 10p11.23, in humans; MAP3K8 is approximately a 57Da protein (467 amino acids). In rat and mouse this protein has similar molecular weights with some conservative substitutions.  MAP3K8 gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity.

For research use only, not for diagnostic or therapeutic use.