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: This review paper focuses on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins, ion channels and transporters, and modifying protein kinase and Ubiquitination/Proteasome System.
Abstract: It has long been recognized that an increase of reactive oxygen species (ROS) can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-κB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt), ion channels and transporters (Ca(2+) and mPTP), and modifying protein kinase and Ubiquitination/Proteasome System.
1,167 citations
TL;DR: Redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1, which is required for the hypoxic induction of physiologically important genes.
Abstract: This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on reactive oxygen species. These heme-based sensors are generally two-domain proteins. Some are hemokinases, while others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1. In yeast and bacteria, regulatory operons coordinate expression of genes responsible for adaptive responses to hypoxia and hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with other identified transcription factors are required for the hypoxic induction of physiologically important genes.
1,167 citations
TL;DR: Administration of the receptor decoy, sRAGE, is likely to sequester ligands, thereby preventing their interaction with other receptors in addition to RAGE, suggesting that, just as RAGE is a multiligand receptor, its ligands are also likely to recognize several receptors in mediating their biologic effects.
Abstract: Advanced glycation end products (AGEs), S100/calgranulins, HMGB1-proteins, amyloid-beta peptides, and the family of beta-sheet fibrils have been shown to contribute to a number of chronic diseases such as diabetes, amyloidoses, inflammatory conditions, and tumors by promoting cellular dysfunction via binding to cellular surface receptors. The receptor for AGEs (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules acting as counter-receptor for these diverse molecules. Engagement of RAGE converts a brief pulse of cellular activation to sustained cellular dysfunction and tissue destruction. The involvement of RAGE in pathophysiologic processes has been demonstrated in murine models of chronic disease using either a receptor decoy such as soluble RAGE (sRAGE), RAGE neutralizing antibodies, or a dominant-negative form of the receptor. Studies with RAGE-/- mice confirmed that RAGE contributes, at least in part, to the development of late diabetic complications, such as neuropathy and nephropathy, macrovascular disease, and chronic inflammation. Furthermore, deletion of RAGE provided protection from the lethal effects of septic shock caused by cecal ligation and puncture (CLP). In contrast, deletion of RAGE had no effect on the host response in delayed-type hypersensitivity (DTH). Despite the lack of effect seen in adaptive immunity by the deletion of RAGE, administration of the receptor decoy, sRAGE, still afforded a protective effect in RAGE-/- mice. Thus, sRAGE is likely to sequester ligands, thereby preventing their interaction with other receptors in addition to RAGE. These data suggest that, just as RAGE is a multiligand receptor, its ligands are also likely to recognize several receptors in mediating their biologic effects.
1,167 citations
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TL;DR: The heterotrimeric guanine nucleotide–binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors, which regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.
Abstract: The heterotrimeric guanine nucleotide-binding proteins (G proteins) are signal transducers that communicate signals from many hormones, neurotransmitters, chemokines, and autocrine and paracrine factors. The extracellular signals are received by members of a large superfamily of receptors with seven membrane-spanning regions that activate the G proteins, which route the signals to several distinct intracellular signaling pathways. These pathways interact with one another to form a network that regulates metabolic enzymes, ion channels, transporters, and other components of the cellular machinery controlling a broad range of cellular processes, including transcription, motility, contractility, and secretion. These cellular processes in turn regulate systemic functions such as embryonic development, gonadal development, learning and memory, and organismal homeostasis.
1,164 citations
TL;DR: The recent resolution of crystal structures of heterotrimeric G proteins in inactive and active conformations provides a structural framework for understanding their role as conformational switches in signaling pathways.
1,163 citations