Figure 5. Polyubiquitination of TAK1 at Lys562 is required for the activation of TAK1 and MAPK, but not IKK.
A, mutation in Lys562 residue of TAK1 in IKK, in response to LPS. TAK1-silenced RAW264.7 cells were reconstituted with Flag-tagged TAK1 wild-type (WT) or K(562,563)R mutant. The cells were incubated with LPS for the indicated times, lysed and phosphorylated proteins were analyzed with immunoblotting (n = 3). B and C, expression of the TAK1 K(562,563)R mutant lead to declined TLR4-mediated AP-1 reporter activity, but had no effect on NF-κB reporter activity. Flag-tagged TAK1 wild-type (WT) or K(562,563)R mutant, Renilla-Luc plasmid and either AP-1 or NF-κB reporter were co-expressed in HEK293T cells with or without TLR4-MD2 for 24 h. Relative luciferase activity was measured and normalized with the Renilla activity. Results are averages ± SD of three separate experiments (*, significant difference).