核受体及核受体病

核受体为一类配体依赖性的转录调节蛋白,它们在一级结构及基因结构上具有同源性,属于核受体家族或甾体激素受体超家族。核受体异常或核受体病将导致靶细胞对相应激素的抵抗,在临床上产生激素不敏感或抵抗症。近年来,核受体病的分子缺陷及突变本质已得到初步揭示。     

细胞因子及其受体系统

细胞因子及其受体系统杨鲁（昆明医学院生化教研室，昆明６５００３１）关键词细胞因子，受体细胞因子是由多种细胞产生的可溶性因子，在细胞之间主要传递免疫和造血方面的信息，具有广泛的生理功能。功能的多效性和多重性细胞因子的作用具有多效性和多重性。原先人们认为...     

锌指状结构受体与急性白血病细胞分化

锌指状结构的细胞受体,通过配基（维甲酸,活性维生素Ｄ３等）的活化,形成二聚体,启动转录,促使急性粒细胞立血病细胞在体外和体内向成熟终末细胞分化,为白血病治疗开辟了一种不抑制骨髓机能的新疗法－诱导分化疗法。     

人类NK细胞活化受体的研究进展

近年来,因为一大批活化和抑制性受体在功能和分子水平上得到阐明,使我们对NK细胞尤其是其表面表达的分子有了较为深入的了解。一方面,NK细胞表达HLA-I类分子特异的抑制性受体,由于宿主自身组织细胞表面HLA-I类分子表达正常而使杀伤抑制性受体介导产生的作用占主导地位,因此能使正常细胞免受NK细胞的杀伤;而另一方面,不同的活化受体参与NK细胞介导的细胞毒作用,他们参与人类NK细胞杀伤HLA-I类分子表达减少或缺失的靶细胞。本文主要就NK细胞的活化受体和协同活化受体以及它们的配体作一综述。     

细胞膜表面钙受体

细胞膜表面受体一直是一个针对有机大分子的概念，近年许多研究表明在多种细胞表面存在钙受体，并发现此类受本不但在细胞外游离钙离子浓度的调节中起重要作用，而且与许多生理病理现象密切相关。本简要介绍其概念，分布，结构功能以及生理病理。     

自然杀伤细胞受体的研究进展

自然杀伤细胞（ＮＫ细胞）可表达两类功能相悖的识别受体,即活化受体（ＫＡＲ）和抑制受体（ＫＩＲ）。ＫＩＲ能识别自身细胞上的ＭＨＣⅠ类分子与自身或外来肽形成２的复合物,所产生的抑制信号可阴断ＫＡＲ的活化,以此抑制ＮＫ细胞的细胞毒作用。如果靶细胞失去ＫＩＲ所识别的配体,ＮＫ细胞即可通过ＫＡＲ对靶细胞进行攻击。本文将介绍此类受体的结构及基识别与信号转导机制的研究进展。     

植物NLR免疫受体的识别、免疫激活与信号调控

高等植物进化出大量膜表面和胞内免疫受体以感知各种病原信号,抵御病原物入侵。其中,细胞表面的模式识别受体感知模式分子后激活基础免疫反应,核苷酸结合和富亮氨酸重复蛋白(NLRs)则通过感知病原微生物分泌的效应蛋白激活特异免疫反应,导致超敏反应与细胞死亡。该文主要综述了NLRs对效应蛋白的识别、植物免疫激活及下游信号调控的最新研究进展。     

病毒受体的研究进展

病毒受体是引发宿主受病毒感染的主要决定因素。病毒受体是指位于宿主细胞表面能被病毒吸附蛋白识别并与之结合 ,从而引起病毒感染的分子复合物。病毒吸附于宿主细胞表面是病毒感染的起始环节。而病毒受体与病毒吸附蛋白的结合是有其特异性的 ,即病毒感染细胞具有不同的组织嗜性和宿主范围。1 .病毒受体的本质病毒受体可分为单分子或多分子复合体。从生化角度上来说 ,大多数是蛋白聚糖、脂类或糖脂、糖蛋白 3种类型。硫酸乙酰肝素蛋白聚糖为单纯疱疹病毒的受体 ,多瘤病毒和正粘病毒的受体为糖蛋白及糖脂的神经节苷脂。部分病毒受体是细胞表…     

甜味机制的研究进展

甜味的感受细胞是味觉细胞,味觉细胞是个双极细胞,味觉受体是一类G蛋白偶联受体,根据甜味物质性质的不同,通过两种途径－－cAMP途径与IP3和DAG途径进行甜味转导。PKA,PKC,味素和转导素在甜味转导中发挥了不同的功能。     

β—受体与炎症

本文主要介绍β－受体结构功能、代谢调节及其与炎症的关系,分析β－受体激动剂、炎症介质及糖皮质激素对β－受体的调节;阐明β－受体激活对炎症过程中血管壁通透性和炎症细胞功能变化的抑制作用及其机制。     

The vitamin D receptor: a primitive steroid receptor related to thyroid hormone receptor

We have previously reported the cloning and sequencing of both the chicken and human vitamin D3 receptor cDNAs. A comparison of their deduced amino acid sequence with that of the other classic steroid hormone receptors and the receptor for thyroid hormone indicates that there are two regions of conservation between these molecules. The first is a 70 amino acid, cysteine-rich sequence (C1), the second region (C2) is a 62 amino acid region located towards the carboxyl terminus of the proteins. In other systems the former has been identified as a region responsible for DNA binding activity, whereas the latter represents the NH2-terminal boundary of the hormone binding domain. We present here evidence utilizing eucaryotic expression of cDNA encoding the hVDR C1 domain, followed by a DNA cellulose chromatography assay, which confirms that the DNA binding activity resides in this region of the receptor for vitamin D3. Additionally, the vitamin D3 receptor contains a 60 amino acid portion at its carboxyl terminus (C3) which exhibits homology with the receptor for thyroid hormone. Conservation in this region of the molecule is found only between homologous or closely related receptors. This indicates a relationship between the vitamin D3 receptor and the receptor for thyroid hormone and may suggest that they evolved from a single primordial gene.     

Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity

We have characterized a series of nonsteroidal progesterone receptor ligands, the tetrahydropyridazines. Compounds in this series, exemplified by RWJ 26819, demonstrate high affinity and unprecedented specificity for the progesterone receptor relative to other steroid hormone receptors. Like steroidal progestins, RWJ 26819 induces binding of the receptor to a progesterone response element in vitro, and stimulates gene expression in and proliferation of T47D human breast cancer cells. When administered to rabbits orally or subcutaneously, the compound induces histological changes in the uterine lining comparable to those induced by levonorgestrel. It also inhibits ovulation in monkeys. Though less potent in cells and in animal models than would be predicted from binding affinity alone, their enhanced selectivity suggests that they could be effectively used in a clinical setting. Most of the tetrahydropyridazines synthesized are progestin agonists or mixed agonists and antagonists in vitro; however, one compound with antagonist activity in the rabbit uterine transformation assay has been identified.     

褪黑素受体

褪黑素是松果体分泌的主要激素,其功能活动通过特异的Ｇ蛋白耦联受体介导,本文综述褪黑素受体 分布、药理学特性,受体的克隆及受体基因结构特点。     

Dopamine D4 receptor oligomerization--contribution to receptor biogenesis

Dopamine D(4) receptors (D(4) Rs) are G protein-coupled receptors that play a role in attention and cognition. In the present study, we investigated the dimerization properties of this receptor. Western blot analysis of the human D(4.2)R, D(4.4)R and D(4.7)R revealed the presence of higher molecular weight immunoreactive bands, which might indicate the formation of receptor dimers and multimers. Homo- and heterodimerization of the receptors was confirmed by co-immunoprecipitation and bioluminescence resonance energy transfer studies. Although dimerization of a large number of G protein-coupled receptors has been described, the functional importance often remains to be elucidated. Folding efficiency is rate-limiting for D(4)R biogenesis and quality control in the endoplasmic reticulum plays an important role for D(4)R maturation. Co-immunoprecipitation and immunofluorescence microscopy studies using wild-type and a nonfunctional D(4.4)R folding mutant show that oligomerization occurs in the endoplasmic reticulum and that this plays a role in the biogenesis and cell surface targeting of the D(4)R. The different polymorphic repeat variants of the D(4)R display differential sensitivity to the chaperone effect. In the present study, we show that this is also reflected by bioluminescence resonance energy transfer saturation assays, suggesting that the polymorphic repeat variants have different relative affinities to form homo- and heterodimers. In summary, we conclude that D(4)Rs form oligomers with different affinities and that dimerization plays a role in receptor biogenesis.     

Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation

Homologous desensitization of beta2-adrenergic receptors has been shown to be mediated by phosphorylation of the agonist-stimulated receptor by G-protein-coupled receptor kinase 2 (GRK2) followed by binding of beta-arrestins to the phosphorylated receptor. Binding of beta-arrestin to the receptor is a prerequisite for subsequent receptor desensitization, internalization via clathrin-coated pits, and the initiation of alternative signaling pathways. In this study we have investigated the interactions between receptors and beta-arrestin2 in living cells using fluorescence resonance energy transfer. We show that (a) the initial kinetics of beta-arrestin2 binding to the receptor is limited by the kinetics of GRK2-mediated receptor phosphorylation; (b) repeated stimulation leads to the accumulation of GRK2-phosphorylated receptor, which can bind beta-arrestin2 very rapidly; and (c) the interaction of beta-arrestin2 with the receptor depends on the activation of the receptor by agonist because agonist withdrawal leads to swift dissociation of the receptor-beta-arrestin2 complex. This fast agonist-controlled association and dissociation of beta-arrestins from prephosphorylated receptors should permit rapid control of receptor sensitivity in repeatedly stimulated cells such as neurons.     

Molybdate-stabilized glucocorticoid receptor: evidence for a receptor heteromer

The composition of the molybdate-stabilized glucocorticoid receptor (GR) complex has been investigated with a monoclonal antibody against the steroid-binding Mr 94 000 (94K) GR protein. It was concluded that one antibody molecule binds one 94K GR molecule. This finding constituted the basis for calculating the number of antibodies bound to the molybdate-stabilized nonactivated GR complex, which has an Mr of 302 000 (302K). Gel filtration on Sephacryl S-400 and density gradient centrifugation showed that only one antibody molecule bound to the molybdate-stabilized GR complex (calculated relative molecular mass for the antibody--molybdate-stabilized GR complex, 456 000; relative molecular mass for one antibody molecule, 157 000). Furthermore, experiments performed with a second antibody immunoprecipitation assay in the presence of an excess of both antibody and GR confirmed the above results. The possibility of steric hindrance not allowing more than one antibody molecule to bind to the molybdate-stabilized GR complex could be excluded. These results suggest that the molybdate-stabilized GR complex with an Mr of 302K only contains one steroid-binding 94K GR molecule and therefore represents a heteromeric complex.