Anti-RIP / RIPK1

0.5mg/ml if reconstituted with 0.2ml sterile DI water. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1), also called RIP, is an enzyme that in humans is encoded by the RIPK1 gene. Members of the TRAF protein family have been implicated in the activation of NF-kappa-B by the TNF superfamily. By yeast 2-hybrid and coimmunoprecipitation studies using mammalian cell extracts, Hsu et al.(1996) showed that RIP interacts with TRADD, TRAF1, TRAF2, and TRAF3. Hartz(2012) mapped the RIPK1 gene to chromosome 6p25.2 based on an alignment of the RIP sequence with the genomic sequence. Stanger et al.(1995) found that overexpression of Rip in mammalian cells induced morphologic changes characteristic of apoptosis. They suggested that RIP may be an important element in the signal transduction machinery that mediates programmed cell death. Protein function: Serine-threonine kinase which is a key regulator of TNF- mediated apoptosis, necroptosis and inflammatory pathways (PubMed:32657447, PubMed:31827280, PubMed:31827281). Exhibits kinase activity-dependent functions that regulate cell death and kinase- independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF- R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1- FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3- MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8. In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591, PubMed:15310755). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage. [The UniProt Consortium]