RIPK3 phosphorylates MLKL

Stable Identifier
R-HSA-5218906
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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RIPK3 was shown to activate mixed lineage kinase domain-like protein (MLKL) by phosphorylation of the threonine 357 and serine 358 residues within the kinase-like domain (Sun L et al. 2012: Wang H et al. 2014). Knocking down of RIPK3 expression in human colon adenocarcinoma (HT29) cell line blocked MLKL phosphorylation (Wang H et al. 2014). These phosphorylation events are critical for necrosis (Sun L et al. 2012; Cai Z et al. 2014; Wang H et al. 2014). Phosphorylation of MLKL is thought to induce a monomer-to-oligomer transition followed by translocation to the membrane-containing compartments (Cai Z et al. 2014; Wang H et al. 2014).

The Reactome event shows that 3 molecules of MLKL are bound to RIPK1:RIPK3 oligomer however the exact stoichiometry of MLKL binding remains unclear.

Literature References
PubMed ID Title Journal Year
22265413 Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase

Sun, L, Wang, H, Wang, Z, He, S, Chen, S, Liao, D, Wang, L, Yan, J, Liu, W, Lei, X, Wang, X

Cell 2012
24703947 Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3

Wang, H, Sun, L, Su, L, Rizo, J, Liu, L, Wang, LF, Wang, FS, Wang, X

Mol. Cell 2014
Participants
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Catalyst Activity
Title
protein serine/threonine kinase activity of (RIPK1:RIPK3)oligomer:3xMLKL [cytosol]
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Orthologous Events
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Created