功能 |
Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.
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總結(jié) |
RIP (Receptor Interacting Protein) is a 74 kDa Ser/Thr kinase which interacts with CD95 (Fas/Apo1) receptor and the tumor necrosis factor receptor (TNFR1). It is a cell death domain adapter protein which can bind to the adapter proteins TRADD, RAID, and TRAF2. RIP contains an N-terminal region with homology to protein kinase, an intermediate domain capable of association with MAPKKK and a C-terminal region containing an intracellular death domain motif. RIP activates both p38 MAP kinase and SAPK families. In vitro, RIP induces apoptosis, as well as SAPK/JNK and NF-kB activation. RIP possesses kinase activity as it autophosphorylates itself on serine and threonine residues.
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