Given our observation that growth factors are important for zVAD.fmk induced death, we examined the contribution of several pathways, including MAPK pathways and Akt, which are known to be activated following growth factor receptor activation (Fig. 2A). Inhibition of Akt (Akt inhibitor VIII) strongly protected the cells from growth factor-sensitive necroptosis induced by zVAD.fmk [16] as well as cell death triggered by bFGF or IGF-1/zVAD.fmk under serum free conditions (Fig. 2B). Inhibition of Akt also protected the cells from growth-factor insensitive death by caused by TNFα (Fig. 2A). Consistent with previous reports, the JNK inhibitor SP600125 protected the cells from both zVAD.fmk and TNFα induced death (Fig. 2A,B and Fig. S2A) [12], [14]. In contrast, inhibition of two other MAPKs, p38 and ERK, previously reported not to be activated during necroptosis [14], did not protect from either zVAD.fmk or TNFα induced death (Fig. 2A).