Anti-RIP3 (phospho T231 + S232) antibody [2D7]

Target data

Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death (PubMed : 27321907, PubMed : 27746097, PubMed : 27917412, PubMed : 28607035, PubMed : 32200799, PubMed : 32296175). Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1 (PubMed : 19590578, PubMed : 22423968, PubMed : 24012422, PubMed : 24019532, PubMed : 24095729, PubMed : 24557836, PubMed : 27321907, PubMed : 27746097, PubMed : 27819681, PubMed : 27819682, PubMed : 32200799, PubMed : 32296175). 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 (PubMed : 24813849, PubMed : 24813850, PubMed : 27321907). 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 (PubMed : 32200799, PubMed : 32296175). Also regulates apoptosis : apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity (PubMed : 27321907). Phosphorylates RIPK1 : RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). In some cell types, also able to restrict viral replication by promoting cell death-independent responses (PubMed : 30635240). 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 (PubMed : 30635240). Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed : 30635240). RIPK3 binds to and enhances the activity of three metabolic enzymes : GLUL, GLUD1, and PYGL (By similarity). These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity).