Necroptosis Antibody Sampler Kit

Necroptosis, a regulated pathway for necrotic cell death, is triggered by a number of inflammatory signals, including cytokines in the tumor necrosis factor (TNF) family, pathogen sensors such as toll-like receptors (TLRs), ischemic injury, and neurodegenerative diseases (1-3). The process is negatively regulated by caspases and is initiated through a complex containing the RIP and RIP3 kinases, typically referred to as the necrosome. Necroptosis is inhibited by a small molecule inhibitor of RIP, necrostatin-1 (Nec-1) (4). RIP is phosphorylated at several sites within the kinase domain that are sensitive to Nec-1, including Ser14, Ser15, Ser161, and Ser166 (5). During necroptosis, RIP3 is phosphorylated at Ser227, leading to recruitment and phosphorylation of MLKL at Thr357 and Ser358 (6). Phosphorylation of MLKL results in its oligomerization and translocation to the plasma membrane, where it affects membrane integrity (7-10). 1.Christofferson, D.E. and Yuan, J. (2010) Curr Opin Cell Biol 22, 263-8. 2.Kaczmarek, A. et al. (2013) Immunity 38, 209-23. 3.Zhou, W. and Yuan, J. (2014) Semin Cell Dev Biol 35, 14-23. 4.Degterev, A. et al. (2008) Nat Chem Biol 4, 313-21. 5.Ofengeim, D. and Yuan, J. (2013) Nat Rev Mol Cell Biol 14, 727-36. 6.Sun, L. et al. (2012) Cell 148, 213-27. 7.Cai, Z. et al. (2014) Nat Cell Biol 16, 55-65. 8.Chen, X. et al. (2014) Cell Res 24, 105-21. 9.Wang, H. et al. (2014) Mol Cell 54, 133-46. 10.Dondelinger, Y. et al. (2014) Cell Rep 7, 971-81.