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- Table of Contents
Facts about Receptor-interacting serine/threonine-protein kinase 2.
Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 via Src tyrosine kinase resulting in NF-kappaB activation by NOD2. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 into IKBKG/NEMO and induces'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB.
Human | |
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Gene Name: | RIPK2 |
Uniprot: | O43353 |
Entrez: | 8767 |
Belongs to: |
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protein kinase superfamily |
CARD3; CARD-containing IL-1 beta ICE-kinase; CARD-containing interleukin-1 beta-converting enzyme (ICE)-associated kinase; CARD-containing interleukin-1 beta-converting enzyme-associated kinase; CARDIAKCCK; EC 2.7.11; EC 2.7.11.1; GIG30; growth-inhibiting gene 30; receptor interacting protein 2; receptor-interacting protein (RIP)-like interacting caspase-like apoptosisregulatory protein (CLARP) kinase; Receptor-interacting protein 2; receptor-interacting serine/threonine-protein kinase 2; receptor-interacting serine-threonine kinase 2; RICK; RICKGIG30; RIP2; RIP-2; RIP2CARD-carrying kinase; RI
Mass (kDA):
61.195 kDA
Human | |
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Location: | 8q21.3 |
Sequence: | 8; NC_000008.11 (89757816..89791064) |
Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.
Cytoplasm.
You are probably curious about RIPK2 phosphorylation. If so, this article will give you an overview. Learn more about IKKs, and how they can be used for RIPK2.
The RIPK2 protein marker has many applications in biology. It acts as a phosphorylation inhibitor and represses RIPK1 enzymatic activities. The RIPK1S25D/K45A line of mice is very similar to RIPK1S25D/K145A. Further studies are needed to determine the mechanism of this phosphorylation inhibitor.
The RIPK2 kinase domain contains the Ser25 amino acid. It is located on the kinase domain, near the Glycine-rich loop. This region is said to coordinate ATP's g-phosphate during catalysis. However, Ser25 is phosphorylated, impairing nucleotide binding and the activation loop. Ser25 also alters the electrostatic properties and interactions with adjacent parts.
The RIPK1 kinasedependent apoptosis serves as a backup mechanism for the immune response to Yersinia infection. The RIPK1 kinasedependent apoptosis sends cell-extrinsic messages to promote optimal antibacterial resistance. During Yersinia infection, Ripk1K45A/K45A chimeras had an elevated bacterial burden in liver and decreased viability. Crossing RIPK1S25D/S25D mice can rescue the multi-organ inflammatory phenotype.
The RIPK2 marker can be used to detect IKBKE's expression in breast cancer cell lines. IKBKE knockdown in MCF-7 breast cancer cells by IKBKE-specific shRNAs, a control shRNA targeting GFP, or gene-suppressive kinase genes located at Iq32 inhibits cell viability.
The RIPK2 gene marker has many uses and can be used to perform a variety different research tasks. Boster Bio has high affinity antibodies that recognize the protein. These antibodies are highly reliable and have been extensively cited in research over the past 25 years. The antibodies have been validated for use in Western blotting, immunohistochemistry, and ELISA. They are also highly specific and can be used to measure RIPK2 levels in cells.
Recent research has shown that RIPK2 phosphorylation is a key factor in the regulation of intestinal microbiota, innate immunity, and bovine adenoviruses. Researchers can study potential therapeutic effects by inhibiting RIPK2 and targeting it with inhibitors. RIPK2 is known to regulate the activity of NODs in inflammatory diseases. Boster Bio's experiments demonstrated that RIPK2 phosphorylation was inhibited in bovine adenoviruses by inhibiting the innate immune system against bacterial infections.
RIPK2 has dual Ser/Thr kinase activation and CARD/CARD domain assembly when activated NODs. Autophosphorylation is a key pathway in activating RIPK2, further targeted by XIAP. RIPK2 also targets polyubiquitination.
Three new inhibitors for RIPK2 phosphorylation phosphorylation are now known. The best activities were seen in ponatinib, sorafenib and regorafenib. These compounds are very potent in inhibiting RIPK2 activation, but their concentrations are very small. This is a promising strategy for tackling GC.
The double mutant RIPK2 RIPK2R36L/R41L mutant failed the NOD2 signaling test in reconstituted cells. Both mutants have the same ability of binding XIAP and inhibiting NOD2 signaling. The failure to repair NOD2 signaling is caused by the R36/R41 fundamental patch and the deeper pocket. The compound that inhibits NOD2 signalsing binds in to the deep pockets.
RIPK1 inhibitors are small molecules that inhibit the activity of a certain protein, a kinase. RIPK1 is involved atypically in tumor necrosis factor receptor signals. A multi-protein complex called a "necrosomome complex" recruits MLKL as a mixed-kinase domain-like protein to the necrosome. This protein causes the rupture of cell membranes, which initiates necroptosis. RIPK1 autophosphorylates itself and RIPK1- and RIPK3-receptors. This process causes necroptosis and death in the affected cells.
RIPK1 inhibiters work by binding to RIPK1's protein domain. They also inhibit the production of certain cytokines and cause death in cells. They have been shown to be safe in healthy volunteers, and to be effective in RA patients. The drug can be purchased in many different forms. One form is available for injection in femoral blood vessels. Several forms of RIPK1 inhibitors are available.
RIPK1 is a key regulator of innate immune signaling. It is also ubiquitinated. Antibodies that target RIPK1 could inhibit this cellular process. As a result, they prevent inflammation by inhibiting the production of cytokines. Boster Bio RIPK1 inhibits myocardium mRNA levels. By inhibiting RIPK1, this agent prevents the release of apoptosis.
The RIPK2 Gene controls the signaling pathways regulating NF kB or MAP kinases. RIPK2-/ cells had defective mitophagy. This leads to increased superoxide, damaged mitochondria, and increased NLRP3 activation. RIPK2 also negatively regulates ULK1, a mitophagy inducer.
To determine the effects of RIPK2 oligomerization we introduced point mutations at critical surface residues within RIP2 constructs. The functional effects of these mutations were then assessed using NFKB luciferase. The resulting mutants displayed decreased cellular activity. This observation is consistent with our previous results. Additionally, we used a Boster Bio-developed test to screen for single mutations of the RIP2 protein.
To study the structure and function of active RIP2-CARD rip2-CARD filaments, we used a reconstitution assay. A SNAP label was added into the protein to increase the stability of the RIP2-CARD rip2-CARD strands. Modifying MAVS protocol was used to prepare seed. The guanidinium gradient was modified to minimize misfolding, precipitation, and misfolding. The MBP-RIP2 filaments remained monomeric for many days without stimulation.
RIPK2 controls NFkB and MAPK signaling. RIPK2 can be rapidly ubiquitinated using polyubiquitin chain, which contains K63-linked motifs. Panda et.al. showed that RIPK2 is ubiquitinated using atypical K27-linked chain, and that the RIPK2 inhibitor suppressed cytokine responses.
RIPK1 is a catalytically inactive protein with a carboxy-terminal death domain, which can interact with death receptor signalling complexes. RIPK1 is the same as RIPK3 and shares the RHIMdomain, which allows them to interact with other cell death adaptors like the TIR domain-containing adaptor inducing IFNb (TRIF). RIPK1/2 is also capable of phosphorylation of other serine proteins, including TAK1, SHARPIN, and RNA-sequencing.
RIP kinase inhibitors have demonstrated anti-inflammatory effects in preclinical models and phase I/II clinical trials. These results indicate that these small molecule inhibitors can be used to treat inflammation and chronic inflammation. More research is needed to fully understand the roles of RIP kinases in cell fate, innate immunity, and innate immunity. By understanding the molecular mechanisms of RIP kinase activation in TAK1 or SHARPIN-deficient cells, we can better design effective therapies that treat the underlying causes of inflammation.
PMID: 9575181 by Inohara N., et al. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis.
PMID: 9642260 by McCarthy J.V., et al. RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase.