Signaling pathway for the cytoprotective effect of STI571 in TRAIL-treated colon cancer cells. In addition to induce classical apoptotic cascade elicited by caspases, TRAIL-induced apoptosis in colon cancer cells requires p38 and JNK activation. We propose both kinase activation by TRAIL relies on activation of c-Abl, and the downstream targeting molecule p73. Abrogating c-Abl activity by STI571 can reduce TRAIL-mediated stress kinase activation and reduce cell apoptosis. Other signaling cascades and molecules involved in the TRAIL-induced stress kinases activation, such as TRAF2, RIP1, and MEKK1/MEKK4, cannot be excluded.