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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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Journal ArticleDOI
22 Jul 1993-Nature
TL;DR: The Ras polypeptide and the amino-terminal regulatory domain of Raf-1 are shown to interact, directly in vitro and in a yeast expression system, and Mutations in and around the Ras effector domain impair Ras binding to Raf- 1(1-257) and Ras transforming activity in parallel.
Abstract: In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce growth and differentiation signals initiated by tyrosine kinases. The Ras polypeptide and the amino-terminal regulatory domain of Raf-1(residues 1–257) are shown to interact, directly in vitro and in a yeast expression system. Raf-1(1-257) binds GTP-Ras in preference to GDP-Ras, and inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1(1-257) and Ras transforming activity in parallel.

844 citations

Journal ArticleDOI
30 May 1997-Cell
TL;DR: It is found that FRS2 is myristylated and that this modification is essential for membrane localization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK activation.

844 citations

Journal ArticleDOI
TL;DR: It is found that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs), and SCFAs produced by the gut microbiota modulate blood pressure via OlfR78 and Gpr41.
Abstract: Olfactory receptors are G protein-coupled receptors that mediate olfactory chemosensation and serve as chemosensors in other tissues. We find that Olfr78, an olfactory receptor expressed in the kidney, responds to short chain fatty acids (SCFAs). Olfr78 is expressed in the renal juxtaglomerular apparatus, where it mediates renin secretion in response to SCFAs. In addition, both Olfr78 and G protein-coupled receptor 41 (Gpr41), another SCFA receptor, are expressed in smooth muscle cells of small resistance vessels. Propionate, a SCFA shown to induce vasodilation ex vivo, produces an acute hypotensive response in wild-type mice. This effect is differentially modulated by disruption of Olfr78 and Gpr41 expression. SCFAs are end products of fermentation by the gut microbiota and are absorbed into the circulation. Antibiotic treatment reduces the biomass of the gut microbiota and elevates blood pressure in Olfr78 knockout mice. We conclude that SCFAs produced by the gut microbiota modulate blood pressure via Olfr78 and Gpr41.

844 citations

Journal ArticleDOI
TL;DR: The regulation of cellular function by hormones and extracellular molecules, which bind to cell surface receptors, is initiated by signal transduction mech­ anisms at the plasma membrane that lead to the generation of intracellular signals, or second messengers.
Abstract: The regulation of cellular function by hormones and extracellular molecules, which bind to cell surface receptors, is initiated by signal transduction mech­ anisms at the plasma membrane that lead to the generation of intracellular signals, or second messengers. These second messengers interact with specific target molecules to initiate a cascade of biochemical events leading to a change in cellular function. A variety of intracellular second messengers, including divalent metals, phospholipid metabolites, and cyclic nucleotides, are known to be generated in response to extracellular stimuli. Calcium acts as an intra­ cellular second messenger in species as diverse as yeast to humans and is involved in cellular processes ranging from contraction to secretion to gene expression. Elevation of cytosolic calcium can occur by influx via regulated ion channels and transporters, or by release from intracellular stores via recep­ tor-generated second messengers (Figure 1). Cells contain a number of intra­ cellular calcium-binding proteins, and in most cell types, the major calcium­ binding protein is calmodulin (44, 91), an -17 kDa, heat-stable protein that binds four calcium ions with an overall high affinity of -1 11 M. This complex of 4(Ca)-calmodulin activates downstream targets. Although the importance of calcium as an intracellular messenger has been long recognized, identifica-

844 citations

Journal ArticleDOI
01 Jan 1998-Nature
TL;DR: It is concluded that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in K SHV-mediated oncogenesis.
Abstract: The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kaposi's sarcoma pathogenesis by stimulating angiogenesis. The G-protein-coupled receptor encoded by an open reading frame (ORF 74) of KSHV is expressed in Kaposi's sarcoma lesions and in PEL and stimulates signalling pathways linked to cell proliferation in a constitutive (agonist-independent) way. Here we show that signalling by this KSHV G-protein-coupled receptor leads to cell transformation and tumorigenicity, and induces a switch to an angiogenic phenotype mediated by vascular endothelial growth factor, an angiogenesis and Kaposi's-spindle-cell growth factor. We find that this receptor can activate two protein kinases, JNK/SAPK and p38MAPK, by triggering signalling cascades like those induced by inflammatory cytokines that are angiogenesis activators and mitogens for Kaposi's sarcoma cells and B cells. We conclude that the KSHV G-protein-coupled receptor is a viral oncogene that can exploit cell signalling pathways to induce transformation and angiogenesis in KSHV-mediated oncogenesis.

842 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20232,989
20225,166
20213,971
20204,179
20194,445
20184,585