FIGURE 5.

SHP2 knock-out blunts TNF-induced dephosphorylation of ASK1. MLEC from SHP2-lox/lox mice were infected with adenovirus-expressing LacZ or Cre. a, 36 h post-infection, cells were serum-starved for 12 h followed by treatment with IFN-γ (10 ng/ml) for the indicated times. Cre-mediated deletion of SHP2, IFN-γ-induced phosphorylation of JAK2, and ASK1 was determined by the respective antibodies. b, 48 h post-infection, EC were treated with TNF (10 ng/ml) for the indicated times. TNF-induced SHP2 activation (pY542) and ASK1 dephosphorylation at Tyr(P)-718 (pY718) were determined by phospho-specific antibodies. c, ASK1-JNK signaling was determined by Western blot with phospho-specific antibodies recognizing active forms of ASK1 (pT845) and p-JNK1/2.