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 .

Receptor-interacting serine/threonine-protein kinase 3 (EC 2.7.11.1) (RIP-like protein kinase 3) (Receptor-interacting protein 3) (RIP-3) (mRIP3)

q9qzl0

Mouse

WB

WB 1:1000

~54 kD

Rabbit

50mM Tris-Glycine(pH 7.4), 0.15M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

Store at -20°C. Stable for 12 months from date of receipt.