After establishing the role of RIP1 kinase-dependent signaling to Akt in L929 cells, we sought to expand our study to other cell types that are known to undergo necroptotic cell death. Fas-associated protein with death domain (FADD)-deficient Jurkat T lymphocytes and the macrophage cell lines (J774A.1 and RAW264.7) are other models of necroptosis, which can be induced by stimulation with TNFα or zVAD.fmk, respectively [17]. Similar to L929 cells, a RIP1 kinase dependent increase in the phosphorylation of Thr308 on Akt occurred during necroptosis (Fig. 8B,D,F) in these cell types. Furthermore, TNFα mRNA levels were increased in each of these cell types during necroptosis and efficiently inhibited by both RIP1 and Akt inhibitors (Fig. 8A,C,E). However, inhibition of Akt did not protect these cells from death (Fig. S9A,B,C). These results indicate that regulation of autocrine TNFα synthesis and necroptosis-associated inflammatory signaling may be a more important function of Akt pathway activation by RIP1 kinase in multiple cell types compared to its contribution to cell death.