Figure 2. Klotho overexpression attenuates the ASK1-signalosome - p38 pathway. (A) Overexpression of Klotho mediates increased levels of the inhibitory (SH)2Trx-ASK1 complex. Western blot analysis of the levels of Trx co-immunoprecipitated with anti-ASK1 antibody in liver extracts of Klotho overexpressing (EFmKL46) and wild-type (WT Hyb) mice. (B, C) MKK3/MKK6 activity is downregulated in the Klotho overexpressing models. Western blot analysis of levels of the MKK3/6 P-Ser189/207 in livers of (B) Klotho overexpressing EFmKL46 (#29, 30, 31) and wild-type (WT Hyb; #26, 27, 28) mice and (C) Klotho overexpressing EFmKL48 (#652, 653, 654, 655); and (D) p38 MAPK activity is downregulated by Klotho overexpression. Western blot analysis of levels of p38 MAPK catalytic site amino acids (P-Thr180/Tyr182 ) in livers of WT Hyb (#26,27,28) Klotho over-expressing mice (EFmKL46 ; #29,30,31).