Using Akt inhibitors, knockdown of Akt isoforms, and the expression of Akt mutants, we showed that necroptotic activation of Akt is indispensable for this form of cell death in L929 cells. We also investigated downstream Akt-dependent pathways that contribute to necroptosis. First, we demonstrated that selective necroptotic phosphorylation of Thr308 of Akt is sufficient to increase its activity towards a number of known substrates and Akt effector pathways such as the mTORC1 pathway, which, in turn, contributes to cell death. Second, our data suggested that Akt activation provides a pivotal link connecting RIP1 kinase to known downstream signaling and execution events in necroptotic L929 cells, namely, JNK activation and autocrine TNFα synthesis, a critical event in necroptosis in L929 cells [15].