RIPK3 is phosphorylated

Stable Identifier
Reaction [transition]
Homo sapiens
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RIPK1:RIPK3 complex formation further potentiates kinase activation through autophosphorylation and/or cross-phosphorylation, propagating the pronecrotic signal. RIPK1, RIPK3 and their kinase activities were shown to be essential for regulated necrosis (Degterev A et al. 2008; Cho YS et al. 2009). RIPK3 kinase-dead mutant (K50A) was found to function as a dominant negative mutant, which blocked TNF-alpha induced necrotic pathway in human colorectal adenocarcinoma HT-29 cells (He S et al. 2009). Mutation of the RIP homotypic interaction motif (RHIM) of RIP3 abrogated RIP1 phosphorylation by RIPK3, suggesting that RIPK1 phosphorylation by RIP3 is dependent on the formation of a RIP:RIP3 complex (Sun X et al. 2001).

Phosphorylation on Ser227 is thought to mediate recruitment and activation of mixed-lineage kinase domain-like (MLKL), a crucial downstream substrate of RIP3 in the necrosis pathway (Sun et al. 2012; Chen et al. 2013).

Literature References
PubMed ID Title Journal Year
19524513 Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation

Cho, YS, Challa, S, Moquin, D, Genga, R, Ray, TD, Guildford, M, Chan, FK

Cell 2009
24059293 Positive and negative phosphorylation regulates RIP1- and RIP3-induced programmed necrosis

McQuade, T, Cho, Y, Chan, FK

Biochem. J. 2013
Participant Of
Catalyst Activity
Catalyst Activity
protein serine/threonine kinase activity of RIPK1:RIPK3 [cytosol]
Physical Entity
Orthologous Events