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Receptor
About: Receptor is a research topic. Over the lifetime, 159318 publications have been published within this topic receiving 8299881 citations.
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TL;DR: Results define SARA as a component of the TGFbeta pathway that brings the Smad substrate to the receptor, and mutations in SARA that cause mislocalization of Smad2 inhibit TGF beta-dependent transcriptional responses, indicating that the regulation of SmAD localization is important for TGFBeta signaling.
986 citations
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TL;DR: Evidence is presented that the 9.5S receptor is extranuclear and involved in estrogen uptake, whereas the nuclear 5S complex, probably responsible for hormone retention and growth initiation, is formed from the 9-5S complex by a process which consumes 9.
Abstract: During the past ten years much information has been accumulated concerning the interaction of tritilated estrogens with hormone-dependent tissues. Their striking affinity for estradiol, both in vivo'-5 and in vitro,6-9 first suggested that such target tissues as uterus, vagina, and anterior pituitary possess unique components called "estrogen receptors." Strong but reversible association of hormone with receptor, without chemical transformation of the steroid molecule, appears to be a primary step in the uterotrophic process, not affected by such inhibitors of early estrogen response as puromycin or actinomycin D.1 The interaction of estradiol with target tissues involves two distinct phenomena uptake and retention; the latter process, but not the former, becomes saturated in vivo if the hormone administered exceeds the physiological level. 1 Centrifugal fractionation experiments"0-14 demonstrate two sites of estrogen binding in uterine cells. As confirmed by autoradiography,1' 16 most estradiol, both in endometrium and in myometrium, resides in the nuclei, but a certain amount is bound to a macromolecular substance appearing in the supernatant fraction. Toft and Gorski'7 made the important observation that the radioactive estradiol-receptor complex in the supernatant fraction can be characterized by ultracentrifugation in sucrose density gradients where it migrates with a sedimentation coefficient of 9.5S; disruption of the complex by proteases but not by nucleases suggests that the receptor substance is a protein. We have confirmed these findings and have observed further8-20 that a different estradiol-receptor complex, sedimenting at about 5S, cani be extracted from uterine nuclei by cold 0.3 Ml KC1, which solubilizes little uterine DNA.2' Although the 9.5S complex does not appear to be a simple aggregate of the 5S, the two receptor substances show many similar characteristics, discussed in more detail elsewhere.22 An important difference is the ability of the 9.5S complex to form spontaneously on addition of tritiated estradiol to supernatant fraction;'9 20, 23 the 5S complex is not produced by adding estradiol to nuclear extract,24 although it can be formed in the whole homogenate. This paper presents evidence that the 9.5S receptor is extranuclear and involved in estrogen uptake, whereas the nuclear 5S complex, probably responsible for hormone retention and growth initiation, is formed from the 9.5S complex by a process which consumes 9.5S receptor and which is retarded at low temperature. Materials and Methods.-These investigations used estradiol-6, 7-H3 (spec. act. 57.4 c/mmole), KRH buffer (pH 7.3, Krebs-Ringer-Henseleit-glucose, containing in gm/liter: NaCl, 8.0; KCI, 0.20; Na2HPO4 7H20, 1.73; KH2PO4, 0.20; CaC12, 0.10; MgC12, 0.048; and glucose, 1.0), and Tris-EDTA buffer (pH 7.4, 0.01 Al 2-amino-2-hydroxymethyl-1,3-propanediol plus 0.0015 M4 ethylenediaminetetraacetic acid, disodium salt).
983 citations
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TL;DR: Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing.
Abstract: Understanding how signals are integrated to control natural killer (NK) cell responsiveness in the absence of antigen-specific receptors has been a challenge, but recent work has revealed some underlying principles that govern NK cell responses. NK cells use an array of innate receptors to sense their environment and respond to alterations caused by infections, cellular stress, and transformation. No single activation receptor dominates; instead, synergistic signals from combinations of receptors are integrated to activate natural cytotoxicity and cytokine production. Inhibitory receptors for major histocompatibility complex class I (MHC-I) have a critical role in controlling NK cell responses and, paradoxically, in maintaining NK cells in a state of responsiveness to subsequent activation events, a process referred to as licensing. MHC-I-specific inhibitory receptors both block activation signals and trigger signals to phosphorylate and inactivate the small adaptor Crk. These different facets of inhibito...
980 citations
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TL;DR: Loss of gamma chain does not appear to perturb T cell development, since both thymic and peripheral T cell populations appear normal, and these mice represent an important tool for evaluating the role of these receptors in humoral and cellular immune responses.
979 citations
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TL;DR: The three‐dimensional structure of the oestrogen receptor beta isoform (ERβ) ligand‐binding domain (LBD) in the presence of the phyto‐oestrogen genistein and the antagonist raloxifene is reported.
Abstract: Oestrogens exert their physiological effects through two receptor subtypes. Here we report the three-dimensional structure of the oestrogen receptor beta isoform (ERbeta) ligand-binding domain (LBD) in the presence of the phyto-oestrogen genistein and the antagonist raloxifene. The overall structure of ERbeta-LBD is very similar to that previously reported for ERalpha. Each ligand interacts with a unique set of residues within the hormone-binding cavity and induces a distinct orientation in the AF-2 helix (H12). The bulky side chain of raloxifene protrudes from the cavity and physically prevents the alignment of H12 over the bound ligand. In contrast, genistein is completely buried within the hydrophobic core of the protein and binds in a manner similar to that observed for ER's endogenous hormone, 17beta-oestradiol. However, in the ERbeta-genistein complex, H12 does not adopt the distinctive 'agonist' position but, instead, lies in a similar orientation to that induced by ER antagonists. Such a sub-optimal alignment of the transactivation helix is consistent with genistein's partial agonist character in ERbeta and demonstrates how ER's transcriptional response to certain bound ligands is attenuated.
979 citations