(A) The HA-tagged C-TAK1 construct and the FLAG-tagged Mitf point mutants were transfected in 293T cells and complexes from whole-cell lysates were immunoprecipitated with FLAG antibody and analyzed by immunoblot with the indicated antibodies. Real-time RT-PCR from (B) RAW 264.7 c4 cells that were either mock transfected, transiently transfected with full length C-TAK1 **p<0.001 vs. M-CSF mock transfected, **p<0.003 vs. M-CSF C-TAK1 transfected or (C) full length C-TAK1 containing the D196N mutant or Mitf mutant M105A/L178A. Cells were stimulated with M-CSF or M-CSF and RANKL for 5 days. **p<0.0015 vs. RANKL mock transfected, ***p<0.0001 vs. RANKL mock transfected. (D) RAW 264.7c4 cells were either mock-transfected or transfected with wt full-length C-TAK1, D196N C-TAK1, wt FLAG-Mitf or FLAG-Mitf M105/L178A. Cells were cultured in M-CSF and RANKL for 7 d. The number of multinuclear cells (greater than 2 nuclei/cell) was counted and the results of two experiments performed in triplicate are shown. **p<0.007 vs. D196N and **p<0.008 vs. FLAG-Mitf.