M受体亚型与G蛋白

５种不同的Ｍ受体亚型的基因已被克隆，用免疫沉淀法观察了它们在体内的分布；Ｇ蛋白调节许多膜受体介导的细胞内功能，在牛的中枢神经系统中发现至少有５种独立的Ｇ蛋白，且每种Ｇ蛋白都由３个亚基构成。实验表明，５种Ｍ受体亚型通过不同的Ｇ蛋白，可同时与ｃＡＭＰ改变和ＰＩ翻转发生偶联作用。     

G蛋白对离子通道的调控

Ｇ蛋白对离子通道的调控鲍国斌濮璐裴钢（中国科学院上海细胞生物学研究所,上海２０００３１关键词Ｇ蛋白Ｇ蛋白偶联受体离子通道Ｇ蛋白（Ｇｐｒｏｔｅｉｎ）由α、β、γ三个亚基组成,位于细胞膜的胞液侧。Ｇα亚基具有ＧＴＰ酶活性,使Ｇ蛋白偶联受体和效应分子发生可...     

溶血磷脂酸受体及下游信号通路在心脏细胞生长中的调节作用

溶血磷脂酸（1ysophosphatidic acid,LPA）是一种十分活跃的磷脂信号分子,具有广泛的生物学效应,包括诱导神经轴突回缩、应力纤维形成、促进血小板凝集、诱导平滑肌收缩、刺激血管平滑肌细胞增殖等。LPA通过其受体及耦联的G蛋白调节细胞内信号途径,介导各种生物学效应。心脏组织中存在多种LPA受体亚型,尤其受体LPAl亚型在心脏组织中的含量仅次于脑,位居第二,暗示LPA在心脏中有重要的生物学功能。本文着重对LPA的5种受体亚型的组织分布、与G蛋白的耦联和对第二信使的活性调节,以及LPA及其受体亚型对心脏细胞的生长调节作一综述。     

肾上腺素受体的生物进化

肾上腺素受体在生物进化的过程中最先出现的是β－肾上腺素受体,此后才出现了α－肾上腺素受体。肾上腺素受体亚型的多样化分化是伴随大脑神经系统的发育而进行的,提示肾上腺素受体的各亚型的进一步分化很有胆对高级神经系统的精细调节功能不断趋于完善的一种适应,同时也预示可能还有其它肾上腺素受体亚型存在。     

前列腺素及其受体与哺乳动物的生殖

前列腺素（ＰＧ）是一类二十碳脂肪酸的衍生物,作为细胞间信号分子广泛分布于各种组织。ＰＧ受体按结合特异性和不同的生理、药理作用可分为ＥＰ－ＦＰ等型,ＥＰ受体又可分为四种亚型。它们者是与Ｇ蛋白偶联的跨膜蛋白。ＰＧ及其受体在哺乳动物生殖过程中发挥着着急而复杂的调节作用。卵泡产生的ＰＧ是排卵所必需的;ＰＧＦ２α参与黄体退化;各种ＰＧＥ受体胚胎着床过程中特异性表达;ＰＧ在分娩过程中也是必不可少的。     

G蛋白βγ亚单位介导的信号转导途径

跨膜信息传递有关的Ｇ蛋白由α、β和γ亚单位所组成,受体激动后,引起ＧＴＰ与α亚单位结合,导致Ｇα与Ｇβγ分离。近年来发现Ｇα、受体本射和许多效应分子如Ｋ＾＋通道、Ｇａ＾２＋通道、磷脂酶Ｃ－β、腺苷酸环化酶、酷氨酸、ＭＡＰＫ和受体激酶等都受Ｇβγ的调节,Ｇβγ同Ｇα一样均可引起效应蛋白的激活,在细胞信号转导中起同样重要作用,共同介导一系列的生物学效应。     

去甲肾上腺素引起的α1肾上腺素受体三种亚型脱敏过程的差异

将含有α１肾上腺素受体三种亚型的全长ｃＤＮＡ质粒分别转染到人胚肾脏细胞（ＨＥＫ２９３）,α１Ａ－,α１Ｂ－和α１Ｄ－ＡＲ在ＨＥＫ２９３细胞株上得到高水平稳定表达,用＾３Ｈ－ｉｎｏｓｉｔｏｌ标记和柱层析法测定细胞磷酸肌醇积。观察在去甲肾上腺素长期作用下α１三种受体亚型介导磷酸肌醇蓄积敏感性降低的差别。     

β肾上腺素能受体的基因结构

β肾上腺素能受体属于Ｇ蛋白偶联受体,分为β１,β２、β３受体亚型,这些亚型具有相似的高级结构。各个亚型的基因克基因克隆表明它们由不同的基因编码。不同亚型的基因具有明显的同源性。     

α2肾上腺素受体的结构及其生物学功能

α2肾上腺素受体为七次跨膜的G蛋白偶联受体。该文介绍了有关α2肾上腺素受体的分型、结构和生物学功能的研究进展。     

细胞因子受体的组成,结构功能及信号传导机制

细胞因子受体种类繁多,分属于不同受体超家族。活化受体的功能可分为：ＰＴＫ型受体或其结合蛋白具有ＰＴＫ活性、丝／苏氨酸蛋白激酶型受体以及与Ｇ蛋白耦联的受体等。不同受体与其配体结合后,通过对受体后信号传导成分的可逆的磷酸化反应传递信号,最终通过对其终端成分,如酶活力、基因表达、细胞骨架蛋白的功能、膜通透性等的调节,导致细胞的生物效应。     

Subtypes of alpha 1- and alpha 2-adrenergic receptors.

The adrenergic receptors are members of the superfamily of G protein-coupled receptors. There are three major types of adrenergic receptors: alpha 1, alpha 2, and beta. Each of these three major types can be divided into three subtypes. Within the alpha 1-adrenergic receptors, alpha 1A and alpha 1B subtypes have been defined pharmacologically on the basis of reversible antagonists, such as WB4101 and phentolamine, and the irreversible antagonist chloroethylclonidine. In at least some tissues the mechanism of action of the alpha 1A subtype is related to activation of a calcium channel, whereas the alpha 1B receptor exerts its effect through the second messenger inositol trisphosphate. Both of these receptor subtypes as well as a third, the alpha 1C, have been identified by molecular cloning. Three pharmacological subtypes of the alpha 2-adrenergic receptor have also been identified. Prototypic tissues and cell lines in continuous culture have been developed for each of these subtypes, which facilitated their study. The definition of the alpha 2 subtypes has been based on radioligand binding data and more limited functional data. All three subtypes have been shown to inhibit the activation of adenylate cyclase and thus reduce the levels of cAMP. Three alpha 2-adrenergic receptor subtypes have been identified by molecular cloning in both the human and rat species. There is reasonable agreement between the pharmacological identified subtypes and those identified by molecular cloning.     

The Basic Types of the Seedling of the Chinese Gramineae in Relation to Systematics

Investigations have been made on the mode of development and various characteristics of seedling of 203 grass species representing over 76 genera and 22 tribes. The correlation between important characteristics and their main formative conditions in distribution area and habitat were discussed. According to the various developmental forms of the embryo axis and root system, the seedlings of grasses may be divided into three main types: Bambusoid, Festucoid and Panicoid. And according to characteristics of seedling leaves and adventitious roots, these types may be further divided into seven subtypes: True Bambusoid, Oryzoid, Arundinoid, Stipoid, Festucoid, Eragrostoid and True Panicoid. in this study, the different types of seedlings have been found to be associated with other characteristics of embryo and adult plant; and on these grounds, the genera of the Gramineae are grouped into seven corresponding subfamilies: Bambusoideae, Oryzoideae, Arundinoideae, Stipoideae, Festucoideae, Eragrostoideae and Panicoideae.     

Prostaglandin receptors: advances in the study of EP3 receptor signaling

Prostaglandin (PG) E(2) produces a broad range of physiological and pharmacological actions in diverse tissues through specific receptors on plasma membranes for maintenance of local homeostasis in the body. PGE receptors are divided into four subtypes, EP1, EP2, EP3, and EP4, which have been identified and cloned. These EP receptors are members of the G-protein coupled receptor family. Among these subtypes, the EP3 receptor is unique in its ability to couple to multiple G proteins. EP3 receptor signals are primarily involved in inhibition of adenylyl cyclase via G(i) activation, and in Ca(2+)-mobilization through G(beta)(gamma) from G(i). Along with G(i) activation, the EP3 receptor can stimulate cAMP production via G(s) activation. Recent evidence indicates that the EP3 receptor can augment G(s)-coupled receptor-stimulated adenylyl cyclase activity, and can also be coupled to the G(13) protein, resulting in activation of the small G protein Rho followed by morphological changes in neuronal cells. This article focuses on recent studies on the novel pathways of EP3 receptor signaling.     

Structure-function analysis of muscarinic acetylcholine receptors

The structural basis underlying the G protein coupling selectivity of different muscarinic receptor subtypes was analyzed by using a combined molecular genetic/biochemical approach. These studies led to the identification of key residues on the receptors as well as the associated G proteins that are critically involved in determining proper receptor/G protein recognition. Mutational analysis of the m3 muscarinic receptor showed that most native cysteine residues are not required for productive receptor/G protein coupling. The putative extracellular disulfide bond was found to be essential for efficient trafficking of the receptor protein to the cell surface but not for receptor-mediated G protein activation.     

Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes.

Relatively little is understood concerning the mechanisms by which subtypes of receptors, G proteins and effector enzymes interact to transduce specific signals. Through expression of normal, hybrid and deletion mutant receptors in Xenopus oocytes, we determined the G protein coupling characteristics of the functionally distinct m2 and m3 muscarinic acetylcholine receptor (mAChR) subtypes and identified the critical receptor sequences responsible for G protein specificity. Activation of a pertussis toxin insensitive G protein pathway, leading to a rapid and transient release of intracellular Ca2+ characteristic of the m3 receptor, could be specified by the transfer of as few as nine amino acids from the m3 to the m2 receptor. In a reciprocal manner, transfer of no more than 21 residues from the m2 to the m3 receptor was sufficient to specify activation of a pertussis toxin sensitive G protein coupled to a slow and oscillatory Ca2+ release pathway typical of the m2 subtype. Notably, these critical residues occur within the same region of the third cytoplasmic domain of functionally distinct mAChR subtypes.     

Functional screening of adrenergic receptors by measuring intracellular calcium using the FlexStation scanning fluorimeter

In this study we test whether functional screening of compounds to adrenergic G protein-coupled receptors (GPCRs) would provide data that correlated significantly with radiolabeled binding data, thereby permitting researchers to replace expensive radioligand-binding experiments with non-radioactive screening. An increase in intracellular calcium levels represents an important second messenger signal for several recombinant GPCRs. In this study, we describe the affinities of three alpha adrenoceptor antagonists (terazosin, tamsulosin and alfuzosin), determined by monitoring the changes in intracellular calcium levels and comparing them with their radioligand-binding affinities. In addition to determining the functional affinities of the three alpha adrenoceptor antagonists, we evaluate their binding at two alpha adrenoceptor subtypes and optimized the assay for high-throughput screening.     

DGKs与肿瘤的关系及作用机制研究进展

二酰甘油激酶家族(DGKs)通过调节两种脂质信号(甘油二酯和磷脂酸)之间的平衡在信号转导中起重要作用。哺乳动物的DGKs作为由十种亚型构成的蛋白质家族,根据它们的结构特征将其分为五型。这些亚型可以通过已知和/或预测功能的各种调节结构域,清楚地表明其不同的功能和调节机制。目前大量的研究表明DGKs可通过调节机体的免疫功能及调控多种肿瘤相关信号通路从而对肿瘤细胞的增殖、凋亡、转移起作用。本文就DGKs与肿瘤之间关系及作用机制进行综述,以期为肿瘤的治疗提供新的思路和方法。     

G protein-coupled receptors.

The diversity of the G protein-coupled receptor superfamily is now being realised with the molecular cloning of DNA encoding many new receptors and receptor subfamilies. The existing pharmacological definitions of receptor subtypes have been extended dramatically with identification of additional subtypes at the molecular level. Functional analysis of cloned receptors by expression in heterologous cell types has demonstrated that individual receptor subtypes can couple to a variety of different effector systems.     

Effects of different experimental conditions on the PrPSc core generated by protease digestion: implications for strain typing and molecular classification of CJD

The discovery of molecular subtypes of the pathological prion protein PrPSc has provided the basis for a novel classification of human transmissible spongiform encephalopathies (TSEs) and a potentially powerful method for strain typing. However, there is still a significant disparity regarding the understanding and nomenclature of PrPSc types. In addition, it is still unknown whether a specific PrPSc type is associated with each TSE phenotypic variant. In sporadic Creutzfeldt-Jakob disease (sCJD), five disease phenotypes are known, but only two major types of PrPSc, types 1 and 2, have been consistently reproduced. We further analyzed PrPSc properties in sCJD and variant CJD using a high resolution gel electrophoresis system and varying experimental conditions. We found that pH varies among CJD brain homogenates in standard buffers, thereby influencing the characteristics of protease-treated PrPSc. We also show that PrPSc type 1 and type 2 are heterogeneous species which can be further distinguished into five molecular subtypes that fit the current histopathological classification of sCJD variants. Our results shed light on previous disparities in PrPSc typing, provide a refined classification of human PrPSc types, and support the notion that the pathological TSE phenotype is related to PrPSc structure.     

Class discovery analysis of the lung cancer gene expression data

Traditional histological classification of lung cancer subtypes is informative, but incomplete. Recent studies of gene expression suggest that molecular classification can be used for effective diagnostic and prediction of the treatment outcome. We attempt to build a molecular classification based on the public data available from a few independent sources. The data is reanalyzed with a new cluster analysis algorithm. This algorithm allows us to preserve the high dimensionality of data and produce the cluster structure without preliminary selection of significant genes or any other presumption about the relation between different cancer and normal tissue samples. The resulting clusters are generally consistent with the histological classification. However, our analysis reveals many additional details and subtypes of previously defined types of lung cancer. Large histological cancer types can be further divided into subclasses with different patterns of gene expression. These subtypes should be taken into account in diagnostics, drug testing, and treatment development for lung cancer patients.