Mouse Receptor-interacting serine/threonine-protein kinase 3(RIPK3) ELISA kit

Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death. Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1. Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity. Phosphorylates RIPK1: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. In some cell types, also able to restrict viral replication by promoting cell death-independent responses. In response to flavivirus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with ZBP1, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate. Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production.

1. key player in the degenerative process in dystrophin-deficient muscles PMID: 30194302
2. melatonin treatment inhibited the Ripk3-PGAM5-CypD-mPTP cascade and thus reduced cellular necroptosis, conferring a protective advantage to the endothelial system in IR stress. PMID: 29770487
3. Aldehyde dehydrogenase 2 deficiency negates chronic low-to-moderate alcohol consumption-induced cardioprotecion possibly via ROS-dependent apoptosis and RIP1/RIP3/MLKL-mediated necroptosis. PMID: 27840306
4. The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate serine 161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis. PMID: 28176780
5. Deficiency in RIPK3 attenuated serum and lung cytokines, lung injury and neutrophil infiltration and lung and gut apoptosis. These data suggest that RIPK3, in part, is responsible for the systemic inflammatory response in neonatal sepsis. PMID: 29248164
6. RIP3-ablation attenuated oxidative stress, inflammation and apoptosis in astrocytes, which was dependent on AMPKalpha activation. PMID: 29470982
7. The necroptosis-inducing kinase RIPK3 reduces adipose tissue inflammation and glucose intolerance. PMID: 27323669
8. RIP3-mediated signaling is not a critical driver of acute radiation syndrome PMID: 29634408
9. RIPK3 promotes adenovirus type 5 oncolytic activity. PMID: 29238045
10. in Mycobacterium tuberculosis-infected macrophages, mitochondria are an essential platform for induction of necrosis by activating RIPK3 function and preventing caspase 8-activation. PMID: 28401933
11. Ripk3 promotes mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac ischemia reperfusion injury. PMID: 28732308
12. The s report here that male reproductive organs of both Ripk3- and Mlkl-knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. Feeding of wild-type mice with an RIPK1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. PMID: 28807105
13. These data demonstrate a role for RIP3 in promoting in vivo thrombosis and hemostasis by amplifying platelet activation. RIP3 may represent a novel promising therapeutic target for thrombotic diseases. PMID: 28242694
14. Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 and MLKL. Moreover, it inhibits RIPK1 and RIPK3 kinase activity. In vivo Sorafenib protects against TNF-induced systemic inflammatory response syndrome (SIRS) and renal ischemia-reperfusion injury (IRI). PMID: 28661484
15. RIP3-mediated activation of caspase-1 rather than necroptosis-dependent inflammation was responsible for aggressive inflammation in influenza A (H7N9) virus-infected mice. PMID: 28423682
16. we assessed the role of RIP3 in synergy with Caspase-1 in the induction of IL-1beta production in BMDM after either LPS/ATP or Chlamydia muridarum stimulation. The possibility of pyroptosis and necroptosis interplays and the role of RIP3 in IL-1beta production during Chlamydia muridarum infection in BMDM was investigated as well. PMID: 28660207
17. 2-hydroxyglutarate bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. PMID: 28564603
18. Knock-out mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during Serratia marcescens pneumonia. PMID: 28387756
19. our results reveal that the necroptosis adaptor RIPK3 has key anti-inflammatory and anti-tumoral functions in the intestine, and define RIPK3 as a novel colon tumor suppressor PMID: 27344176
20. Ablation of Ripk3 rescues Fadd-deficient mice through two processes: inhibiting necroptosis during embryonic development and restricting massive inflammation during postnatal development, which were segregated by the RIPK3 mutation. PMID: 28445730
21. Impaired Nrf2-dependent redox homeostasis is an important mechanism that promotes cell death downstream of IFN-I and RIP3 signaling in S. Typhimurium-infected macrophages. PMID: 29055012
22. a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c(+) mononuclear phagocytes in a kinase- and necroptosis-independent manner. PMID: 28273458
23. An alternative function for RIPK1/RIPK3 in vascular permeability. PMID: 28151480
24. study identifies a novel role for RIPK1 and RIPK3, a pair of homologous serine/threonine kinases previously implicated in the regulation of necroptosis and pathologic tissue injury, in directing IFN-beta production in macrophages PMID: 28461567
25. this study shows that RIPK1 and RIPK3 account for acute inflammatory responses induced by lipopolysaccharide in vivo; notably, this regulation does not require exogenous manipulation of caspases PMID: 27396959
26. RIPK3 and/or MLKL may exert functions independently of necroptosis. PMID: 27523270
27. These results identify DAI as a link between influenza A virus replication and RIPK3 activation and implicate DAI as a sensor of RNA viruses. PMID: 27746097
28. results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases. PMID: 27756058
29. Mice deficient in RIPK3 or doubly deficient in MLKL and FADD, but not MLKL alone, are more susceptible to influenza A virus than their wild-type counterparts, revealing an important role for RIPK3-mediated apoptosis in antiviral immunity. PMID: 27321907
30. These data suggest that Rip3 plays a role in neurodegeneration and mitochondrial morphology in the absence of mitochondrial division. PMID: 27640145
31. RIPK3 regulates type I IFN both transcriptionally, by interacting with MAVS and limiting RIPK1 interaction with MAVS, and post-transcriptionally. PMID: 28410401
32. Using a mouse model of West Nile virus encephalitis, study shows that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type controls. PMID: 28366204
33. Low RIP3 expression is associated with inflammation in dextran sodium sulfate-induced ulcerative colitis . PMID: 28256024
34. The findings reported here indicate that palmitate induces RIP1/RIP3-dependent necrosis via MLKL-mediated pore formation of RAW 264.7 cells in the plasma membrane, which could provide a new mechanism to explain the link between elevated levels of free fatty acids (FFAs), palmitate in particular, and macrophage death. PMID: 27856241
35. Results demonstrate that RIPK3 restricts malignant myeloproliferation by activating the inflammasome, which promotes differentiation and cell death, and that loss of RIPK3 increases leukemic burden in mice. Reduced RIPK3 expression is observed across several human acute myeloid leukemia subtypes. PMID: 27411587
36. Data identify RIPK3 and the inflammasome as key tumor suppressors in acute myeloid leukemia (AML). PMID: 27411587
37. Results suggest that impaired hepatic proteasome function by alcohol exposure may contribute to hepatic accumulation of RIP3 resulting in necroptosis and steatosis while RIP1 kinase activity is important for alcohol-induced inflammation. PMID: 26769846
38. Study shows that Rip3 mRNA expression is at the highest level in the spleen and duodenum, but lowest level in brain. Protein detection results revealed its localization in different type cells in different tissues that can be either nuclear or cytoplasmic. PMID: 26969469
39. we demonstrate that the phosphorylation of Ser345 is not required for the interaction between RIPK3 and MLKL in the necrosome, but is essential for MLKL translocation, accumulation in the plasma membrane, and consequent necroptosis. PMID: 26024392
40. CHIP is a bona fide negative regulator of the RIPK1-RIPK3 necrosome formation leading to desensitization of TNF-mediated necroptosis PMID: 26900751
41. Data indicate that receptor-interacting serine-threonine kinase 3 (RIPK3) deletion prevents inflammatory phenotypes in CreLysM (lysozyme M) Casp8fl/fl (caspase 8) mice. PMID: 26471282
42. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. PMID: 26726877
43. RIPK3 is an essential molecule to maintain the temporal manner of the normal progression of wound closure PMID: 26451737
44. deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. PMID: 26817517
45. Results identify a crucial role for RIPK3-PGAM5-Drp1/NFAT signalling in NKT cell activation, and further suggest that RIPK3-PGAM5 signalling may mediate crosstalk between mitochondrial function and immune signalling. PMID: 26381214
46. RIPK3 can promote NLRP3 inflammasome and IL-1beta inflammatory responses independent of MLKL and necroptotic cell death PMID: 25693118
47. Data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases. PMID: 25906154
48. Cisplatin stimulates RIP1/RP3/MLKL-dependent necrotic cell death in renal tubules, which finally causes renal dysfunction PMID: 25788533
49. diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage PMID: 25950489
50. Human herpesvirus 1 ICP6 interacts with mouse RIP1/RIP3 through its RHIM domain and forms dimers/oliogmers by its C-terminal R1 domain. PMID: 25674982

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Cytoplasm, cytosol. Nucleus.

Protein kinase superfamily, TKL Ser/Thr protein kinase family

Expressed in embryo and in adult spleen, liver, testis, heart, brain and lung.

KEGG: mmu:56532

STRING: 10090.ENSMUSP00000022830

UniGene: Mm.46612