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Existence of a kinase-independent role of nuclear RIPK1 in the regulation of PARP1 (zeige PARP1 Proteine).
Study identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF (zeige TNF Proteine)-RSC, NFkappaB (zeige NFKB1 Proteine), and MAP kinase (zeige MAPK1 Proteine) signaling systems. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 (zeige CASP8 Proteine) and FADD (zeige FADD Proteine) proteins, and subsequent necrotic cell death during inflammatory TNFalpha (zeige TNF Proteine) stimulation.
New potent RIPK1 inhibitors are reported (GSK2606414 and GSK2656157).
In conclusion, for the first time, we report that TRADD (zeige TRADD Proteine), TRAF2 (zeige TRAF2 Proteine), RIP1 (zeige UQCRFS1 Proteine) and TAK1 (zeige MAP3K7 Proteine) play a role in the regulating TNF-alpha (zeige TNF Proteine) signalling in human myometrium. These findings are of significance given the central role of TNF-alpha (zeige TNF Proteine) in the processes of human labour and delivery.
the in vivo effects were diametrically reversed with RIP3 (zeige RIPK3 Proteine) deletion or RIP1 (zeige UQCRFS1 Proteine) blockade, resulting in marked tumor protection. The dichotomy between the in vivo and in vitro results suggests that the microenvironmental milieu resulting from RIP1 (zeige UQCRFS1 Proteine)/RIP3 (zeige RIPK3 Proteine) signaling is likely responsible for its protumorigenic effects
Shikonin induces glioma cell necroptosis in vitro by reactive oxygen species overproduction and promoting RIP1 (zeige UQCRFS1 Proteine)/RIP3 (zeige RIPK3 Proteine) necrosome formation.
the cytoplasmic retinoic acid receptor gamma (zeige RARG Proteine) (RARgamma) controls receptor-interacting protein kinase (zeige CDK7 Proteine) 1 (RIP1 (zeige UQCRFS1 Proteine))-initiated cell death when cellular inhibitor of apoptosis (cIAP) activity is blocked.
SIRT2 (zeige SIRT2 Proteine) and RIPK1 were localized to the syncytiotrophoblast, villous leukocytes and vasculature in all preterm placentas. A significant reduction in SIRT2 (zeige SIRT2 Proteine) protein expression in both preeclampsia and fetal growth restricted placentas was identified. RIPK1 mRNA expression was significantly increased in preeclampsia placentas. Immunofluorescence identified both SIRT2 (zeige SIRT2 Proteine) and RIPK1 in the cytotrophoblast cytoplasm.
RIPK1 inhibits the transcriptional activity of VDR.
Results show that downregulation of RIP1 (zeige UQCRFS1 Proteine) results in increased resistance to SN38, implying a requirement for RIP1 (zeige UQCRFS1 Proteine) in mediating cytotoxicity through the TNF (zeige TNF Proteine)/TNFR (zeige TNFRSF1A Proteine) signaling pathway.
Pull down experiments with biotinylated Sorafenib show that it binds independently RIPK1, RIPK3 (zeige RIPK3 Proteine) and MLKL. Moreover, it inhibits RIPK1 and RIPK3 (zeige RIPK3 Proteine) kinase activity. In vivo Sorafenib protects against TNF (zeige TNF Proteine)-induced systemic inflammatory response syndrome (SIRS) and renal ischemia-reperfusion injury (IRI).
The study provides genetic evidence that different RIP1 kinase inactive mutations have distinct impacts on the embryogenesis of Fadd-deficient mice.
Excessive death of hepatocytes is a characteristic of liver injury. A new programmed cell death pathway has been described involving upstream death ligands such as TNF (zeige TNF Proteine) and downstream kinases such as RIPK1.
TNFalpha (zeige TNF Proteine)-induced phosphorylation of RIPK1 in the intermediate domain by TAK1 (zeige NR2C2 Proteine) plays a key role in regulating the decision between three distinct mechanisms of cell death: necroptosis, RIPK1-independent and dependent apoptosis.
K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli.
Data show that the kinase activity of receptor-interacting protein kinase (zeige CDK7 Proteine) 1 (RIPK1) is required for Yersinia-induced apoptosis.
p38MAPK (zeige MAPK14 Proteine)/MK2 (zeige KCNA2 Proteine) phosphorylation of RIPK1 is a crucial checkpoint for cell fate in inflammation and infection that determines the outcome of bacteria-host cell interaction.
MK2 (zeige KCNA2 Proteine)-mediated RIPK1 phosphorylation is an important molecular mechanism limiting the sensitivity of the cells to the cytotoxic effects of TNF (zeige TNF Proteine).
An alternative function for RIPK1/RIPK3 (zeige RIPK3 Proteine) in vascular permeability.
these results revealed a novel, kinase-independent function of RIP1, which is essential for not only promoting TCR-induced proliferative responses but also in blocking apoptosis in mature T cells.
Serine-threonine kinase which transduces inflammatory and cell-death signals (necroptosis) 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. 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 necroptosis-inducing complex.
receptor (TNFRSF)-interacting serine-threonine kinase 1
, 1,3,4,5,6-pentakisphosphate 2-kinase
, inositol polyphosphate kinase 1
, inositol-1,3,4,5,6-pentakisphosphate 2-kinase
, inositol-pentakisphosphate 2-kinase
, ins(1,3,4,5,6)P5 2-kinase
, insP5 2-kinase
, cell death protein RIP
, receptor interacting protein
, receptor-interacting protein 1
, receptor-interacting serine/threonine-protein kinase 1
, serine/threonine-protein kinase RIP
, RPA interacting protein delta 2
, RPA interacting protein epsilon
, RPA-interacting protein