Figure 5.

ASK1-JNK/p38 axis regulates sustained Akt activation induced by ADP stimulation and platelet-dependent tumor metastasis. (a) Akt phosphorylation by ADP stimulation in CHO cells exogenously expressing control lacZ or mouse P2Y₁₂ (mP2Y₁₂)-WT. (b) The phosphorylation-defective (T345A) and recycling-defective (P346A) mutants of mP2Y₁₂ lost sustained Akt signaling by ADP stimulation in CHO cells. (c) JNK and p38 inhibition synergistically suppressed sustained Akt signaling induced by ADP stimulation in CHO cells exogenously expressing mP2Y₁₂-WT. (d) Luciferase activity of lung lysates 14 days after i.v. injection of B16F10-luc-G5 cells (Ask1^F/F mice: n=11, Pf4-cre; Ask1^F/F mice: n=10). The data are presented as the mean±s.e.m. *P<0.05. Unpaired Student’s t-tests (d). (e) ASK1-JNK/p38 axis in platelets facilitates ADP-induced Akt activity by phosphorylation of mP2Y₁₂ at Thr345 and platelet-dependent tumor metastasis