The activity of tumor progression locus-2 (TPL2, also known as COT and MAP3K8) is regulated by means of phosphorylation (Stafford MJ et al., 2004; Cho J et al., 2005; Black TM et al., 2007; Robinson MJ et al., 2007). MAP3K8 undergoes phosphorylation on S400 in its C-terminal tail to activate MAP2Ks (MEK1/2) in LPS-stimulated macrophages (Robinson MJ et al., 2007). Different experimental systems have suggested that S400 is either autophosphosphorylated by MAPK3P8 or transphosphorylated (Kane LP et al., 2002; Robinson MJ et al., 2007; Roget K et al, 2012).
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