RIPK3, Receptor interacting serine/threonine kinase 3 or RIP-like protein kinase 3 (human RIPK3 isoform1 theoretical molecular weight 57kDa) is a cytosolic protein with an amino terminal active kinase domain. RIP kinases, RIPK1 and RIPK3 play a central role in the induction of necroptosis, a form of programmed and inflammatory cell death that is caspase-independent (1). Necroptosis is a form of programmed necrosis which is initiated through the activation of RIPK3 by various ligands such as Fas, LPS and TNF. Formation of the necrosome results from the interaction between RIPK1 and RIPK3 mediated through their RIP homotypic interaction motifs (RHIMs) (1, 2). Following necrosome formation, RIPK3 activation leads to the phosphorylation of mixed lineage kinase domain-like protein (MLKL) which induces its oligomerization and translocation to the cell membrane where it alters plasma membrane integrity (2). Loss of membrane integrity results in lytic cell death, release of damage associated molecular patterns (DAMPs) and inflammation (2, 3). Therefore, the interaction of RIPK3 with other RHIM proteins is necessary for the initiation of necroptosis, while the execution phase is dependent on the activation of MLKL (4).
RIPK3 has several phosphorylation sites that are required for its role in necroptosis. For example, serine204 in mouse, which is conserved in the human (serine199), is necessary for necroptosis while serine residues 232 and 227 are both required for RIPK3s interaction with MLKL (2). The core necroptosis proteins RIPK1/RIPK3 and MLKL are implicated in several disease states such as neurodegeneration, cardiovascular, hepatic and pulmonary disease (3).
1. Orozco, S., & Oberst, A. (2017). RIPK3 in cell death and inflammation: the good, the bad, and the ugly. Immunological Reviews. https://doi.org/10.1111/imr.12536
2. Dhuriya, Y. K., & Sharma, D. (2018). Necroptosis: A regulated inflammatory mode of cell death. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-018-1235-0
3. Choi, M. E., Price, D. R., Ryter, S. W., & Choi, A. M. K. (2019). Necroptosis: A crucial pathogenic mediator of human disease. JCI Insight. https://doi.org/10.1172/jci.insight.128834
4. Lee, K.-H., & Kang, T.-B. (2019). The Molecular Links between Cell Death and Inflammasome. Cells. https://doi.org/10.3390/cells8091057
|Product By Gene ID
- Receptor Interacting Serine/Threonine Kinase 3
- EC 18.104.22.168
- receptor-interacting serine/threonine-protein kinase 3
- Receptor-interacting protein 3
- RIP-like protein kinase 3
- receptor-interacting serine-threonine kinase 3