Tpl2 (also known as Cot, officially known as MAP3K8) is constitutively bound to NFKB p105 (p105) which inhibits its MEK kinase activity in resting cells. Proteolysis of p105 frees Tpl2 from p105 and allows subsequent phosphorylation and activation of MEK1. Tpl2 can also activate SEK1 (MAP2K4). Phosphorylation of Tpl-2 is believed to play a role in its activation (Cho et al, 2005; Robinson et al. 2007).
Positions of phosphorylations represented here are inferred from general experimental data (Zheng & Guan, 1994).