Necroptosis | Cell Necrosis Signaling Pathway

Necroptosis

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. 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). RIP is phosphorylated at several sites within the kinase domain that are sensitive to Nec-1, including Ser14, Ser15, Ser161, and Ser166. During necroptosis, RIP3 is phosphorylated at Ser227, leading to recruitment and phosphorylation of MLKL at Thr357 and Ser358. Phosphorylation of MLKL results in its oligomerization and translocation to the plasma membrane, where it affects membrane integrity.

Molecular signaling pathway of necroptosis

Relevent antibodies

Catalog#Product NameReactivityApplication
AMRe21588RIP Rabbit Monoclonal antibodyHumanWB,IHC,IF,IP,ELISA
APRab20453RIP (Phospho Ser166) Rabbit Polyclonal AntibodyHuman,Rat,MouseWB,IHC
AMRe21172MLKL Rabbit Monoclonal antibodyHuman,Mouse,RatWB,IHC,IF,IP,ELISA
AMRe84013Phospho-MLKL(S358) Rabbit MonoclonalHumanWB,IHC
AMM83568RIPK3 Mouse Monoclonal AntibodyHumanIHC
APS0635HRP-conjugated Polyclonal Goat Anti-Rabbit IgG(H+L) Secondary Antibody
AMre80004GAPDH (12R9) Rabbit Monoclonal Antibody

References

  • Christofferson DE, Yuan J. Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol. 2010 Apr;22(2):263-8. [PMID: 20045303].
  • Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, Abbott D, Cuny GD, Yuan C, Wagner G, Hedrick SM, Gerber SA, Lugovskoy A, Yuan J. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008 May;4(5):313-21. [PMID: 18408713].
  • Dondelinger Y, Declercq W, Montessuit S, Roelandt R, Goncalves A, Bruggeman I, Hulpiau P, Weber K, Sehon CA, Marquis RW, Bertin J, Gough PJ, Savvides S, Martinou JC, Bertrand MJ, Vandenabeele P. MLKL compromises plasma membrane integrity by binding to phosphatidylinositol phosphates. Cell Rep. 2014 May 22;7(4):971-81. [PMID: 24813885].
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Flora

Flora is a technical support expert at EnkiLife, familiar with immunology and neuroscience, dedicated to providing customers with high-quality product combinations and technical support to help achieve research in neurodegenerative diseases and other neuroscience areas.

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