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.
Papers published on a yearly basis
Papers
More filters
TL;DR: Another previously unappreciated strategy used by the receptors to regulate intracellular signaling pathways is indicated, which regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways.
Abstract: The transmission of extracellular signals to the interior of the cell is a function of plasma membrane receptors, of which the seven transmembrane receptor family is by far the largest and most versatile. Classically, these receptors stimulate heterotrimeric G proteins, which control rates of generation of diffusible second messengers and entry of ions at the plasma membrane. Recent evidence, however, indicates another previously unappreciated strategy used by the receptors to regulate intracellular signaling pathways. They direct the recruitment, activation, and scaffolding of cytoplasmic signaling complexes via two multifunctional adaptor and transducer molecules, beta-arrestins 1 and 2. This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and likely other cellular functions through a rapidly expanding list of signaling pathways.
1,592 citations
TL;DR: In this paper, the authors discuss cellular genes and disease states associated with activation of the NF-κB pathway and consider therapeutic strategies to prevent the prolonged activation of this pathway, such as glucocorticoids and aspirin.
Abstract: NF-κB comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory response. In addition, NF-κB is also involved in protecting cells from undergoing apoptosis in response to DNA damage or cytokine treatment. Stimulation of the NF-κB pathway is mediated by diverse signal transduction cascades. These signals activate the IκB kinases, IKKα and IKKβ, which phosphorylate inhibitory proteins known as IκB to result in their ubiquitination and degradation by the proteasome. The degradation of IκB results in the translocation of NF-κB from the cytoplasm to the nucleus where it activates the expression of specific cellular genes. As we better understand the regulation of the NF-κB pathway, the potential for inhibiting this pathway has received attention. Agents that inhibit this pathway, such as glucocorticoids and aspirin, can reduce the inflammatory response, while other agents such as dominant negative IκB proteins potentiate the effects of chemotherapy and radiation therapy in the treatment of cancer. Here, we discuss cellular genes and disease states associated with activation of the NF-κB pathway and consider therapeutic strategies to prevent the prolonged activation of the NF-κB pathway.
1,591 citations
TL;DR: Various extracellular informational signals such as those from a group of hormones and some neurotransmitters appear to be passed from the cell surface into the cell interior by two routes, protein kinase C activation and Ca2+ mobilization.
Abstract: Various extracellular informational signals such as those from a group of hormones and some neurotransmitters appear to be passed from the cell surface into the cell interior by two routes, protein kinase C activation and Ca2+ mobilization. Both routes usually become available as the result of an interaction of a single ligand and a receptor and act synergistically to evoke subsequent cellular responses such as release reactions. The signal-dependent breakdown of inositol phospholipids, particularly phosphatidylinositol bisphosphate, now appears to be a key event for initiating these processes.
1,590 citations
TL;DR: It is shown here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro and in vivo and a parallel impairment of glucose tolerance is observed in mice lacking ffar2 or ffar3.
Abstract: Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the SCFA receptors ffar2 (grp43) and ffar3 (gpr41) in GLP-1–secreting L cells, and consistent with the reported coupling of GPR43 to Gq signaling pathways, SCFAs raised cytosolic Ca2+ in L cells in primary culture. Mice lacking ffar2 or ffar3 exhibited reduced SCFA-triggered GLP-1 secretion in vitro and in vivo and a parallel impairment of glucose tolerance. These results highlight SCFAs and their receptors as potential targets for the treatment of diabetes.
1,586 citations
TL;DR: It is shown that overexpression of Klotho in mice extends life span and it is suggested that Klotha-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties.
Abstract: A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.
1,583 citations