Topic
Signal transduction
About: Signal transduction is a research topic. Over the lifetime, 122628 publications have been published within this topic receiving 8209258 citations. The topic is also known as: GO:0007165.
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TL;DR: Evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.
Abstract: Apoptosis signal‐regulating kinase (ASK) 1 was recently identified as a mitogen‐activated protein (MAP) kinase kinase kinase which activates the c‐Jun N‐terminal kinase (JNK) and p38 MAP kinase pathways and is required for tumor necrosis factor (TNF)‐α‐induced apoptosis; however, the mechanism regulating ASK1 activity is unknown. Through genetic screening for ASK1‐binding proteins, thioredoxin (Trx), a reduction/oxidation (redox)‐regulatory protein thought to have anti‐apoptotic effects, was identified as an interacting partner of ASK1. Trx associated with the N‐terminal portion of ASK1 in vitro and in vivo . Expression of Trx inhibited ASK1 kinase activity and the subsequent ASK1‐dependent apoptosis. Treatment of cells with N ‐acetyl‐l‐cysteine also inhibited serum withdrawal‐, TNF‐α‐ and hydrogen peroxide‐induced activation of ASK1 as well as apoptosis. The interaction between Trx and ASK1 was found to be highly dependent on the redox status of Trx. Moreover, inhibition of Trx resulted in activation of endogenous ASK1 activity, suggesting that Trx is a physiological inhibitor of ASK1. The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.
2,377 citations
TL;DR: Roles for PARs are beginning to emerge in haemostasis and thrombosis, inflammation, and perhaps even blood vessel development.
Abstract: How does the coagulation protease thrombin regulate cellular behaviour? The protease-activated receptors (PARs) provide one answer. In concert with the coagulation cascade, these receptors provide an elegant mechanism linking mechanical information in the form of tissue injury or vascular leakage to cellular responses. Roles for PARs are beginning to emerge in haemostasis and thrombosis, inflammation, and perhaps even blood vessel development.
2,354 citations
TL;DR: It is reported that the noncanonical IκB kinase homologs, IKKε (IKKε) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-κB activation, are also essential components of the IRF3 signaling pathway.
Abstract: The transcription factors interferon regulatory factor 3 (IRF3) and NF-kappaB are required for the expression of many genes involved in the innate immune response. Viral infection, or the binding of double-stranded RNA to Toll-like receptor 3, results in the coordinate activation of IRF3 and NF-kappaB. Activation of IRF3 requires signal-dependent phosphorylation, but little is known about the signaling pathway or kinases involved. Here we report that the noncanonical IkappaB kinase homologs, IkappaB kinase-epsilon (IKKepsilon) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-kappaB activation, are also essential components of the IRF3 signaling pathway. Thus, IKKepsilon and TBK1 have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response.
2,328 citations
TL;DR: The proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway, and active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3.
Abstract: BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.
2,321 citations
TL;DR: The recent cloning of a naturally occurring IL-1 receptor antagonist (IL-1ra) has opened new experimental and clinical approaches and reduced the severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.
2,307 citations