Rac1的免疫调节作用及其与疾病的关系

Rho蛋白是一种具有三磷酸鸟苷(GTP)酶活性的小分子蛋白,Rac1是其家族成员之一,是细胞内重要的信号转导分子,在多种细胞的基本功能中发挥分子开关作用.它一方面可参与免疫调节及细胞周期、细胞骨架重排、细胞运动与转移的调节等,另一方面在许多疾病如哮喘、房颤、感染性疾病、肿瘤等中异常表达,且与肿瘤的侵袭和转移密切相关,有可能成为判断肿瘤发展和预后的新指标.     

PTP的结构与功能

蛋白质分子中酪氨酸残基的可逆性磷酸化作为真核生物信号转导的一个重要组成部分,参与了多种细胞功能调节,包括细胞增殖、迁移以及细胞间相互作用等。目前认为这种可逆性的磷酸化调节主要是受控于蛋白酪氨酸激酶(PTK)及蛋白酪氨酸磷酸酯酶(PTP)这两种酶活性的动态平衡。因此,与PTK一样,PTP对于体内各种生命活动起着非常重要的生物学作用。文章综述了近年来PTP在信号转导中的调控作用,特别是其在肿瘤发生、发展过程中的作用、以及其本身的结构与调控的研究进展。     

胞膜窖及其蛋白对离子通道的作用

胞膜窖(caveolae)是存在于多种细胞表面的小凹结构,其标志蛋白小凹蛋白(caveolin)在信号转导中起着中心调控作用.Caveolin可与多种蛋白结合,它与离子通道蛋白结合可调节离子通道的活性,维持机体多种生理活动的平衡.Caveolae可调节钾离子通道的活性,与钠离子通道结合可以调节心肌动作电位的产生,caveolin-i对容积调控氯通道(volume-regulated anion channels,VRAC)也是一个必要条件,caveolin-1和caveolin-3还对动脉平滑肌细胞中的钙离子起平衡调控作用.研究caveolin对离子通道活动的影响对于探索一些生命现象的基本机制将有重要意义.     

低氧诱导因子-1研究进展

低氧诱导因子 1(HIF 1)是在低氧及模拟低氧条件下细胞产生的一种蛋白转录调控因子 ,由α和 β两种亚基组成 ,HIF 1α的磷酸化和非磷酸化状态作用不同。HIF 1涉及的信号转导通路复杂 ,广泛参与哺乳动物细胞低氧诱导性应答 ,在低氧诱导的基因表达调节中起着关键作用。本文就HIF 1的结构、作用、活性调节及在低氧信号转导中的作用等方面的研究进展作一综述     

窖蛋白-1的功能与病毒感染

Caveolin（窖）蛋白家族是与在众多细胞的质膜系统中发现的微结构（caveolae）细胞膜穴样内陷有紧密关联的蛋白家族。Caveolin-1可与多种信号分子相互作用,下调信号分子活性。由于窖蛋白是细胞膜上的重要蛋白,参与细胞内吞作用,从而与一些病毒的感染过程密切相关。本文就该蛋白的结构、功能及与病毒感染的联系等进行综述。     

窖蛋白-1的功能与病毒感染

Caveolin(窖)蛋白家族是与在众多细胞的质膜系统中发现的微结构?(caveolae)细胞膜穴样内陷有紧密关联的蛋白家族。Caveolin-1可与多种信号分子相互作用,下调信号分子活性。由于窖蛋白是细胞膜上的重要蛋白,参与细胞内吞作用,从而与一些病毒的感染过程密切相关。本文就该蛋白的结构、功能及与病毒感染的联系等进行综述。     

膜-细胞骨架连接分子Ezrin与肿瘤转移

Ezrin是ERM(Ezrin/Rad ixin/Moesin)家族的重要成员,是真核细胞膜蛋白-细胞骨架的桥梁分子。参与细胞形态学,细胞黏附、运动、细胞骨架的重塑及信号转导过程。Ezrin在不同肿瘤组织中的表达异常,推测它可能参与肿瘤细胞的侵袭转移,但表达的不一致提示Ezrin在不同肿瘤的进展和转移中发挥着不同的作用。     

多囊蛋白-1的研究进展

多囊蛋白-1（polycystin-1,PC-1）是由多囊肾病基因-1（PKD1）编码的跨膜蛋白,属多囊蛋白家族成员,主要在上皮细胞、内分泌细胞、心肌细胞和骨骼肌细胞上表达。PC-1可与多囊蛋白-2（polycystin-2,PC-2）、踝蛋白、纽蛋白等蛋白结合,参与细胞-细胞、细胞-基质黏附和细胞间信号转导。PC-1可调节肾小管上皮细胞的增殖和分化、介导细胞间的黏附,在肾脏的正常发育和常染色体显性遗传性多囊肾病（ADPKD）发病起重要作用。     

Racl与肿瘤的研究进展

Rho家族在细胞的一些基本功能中起着分子开关的作用,参与了细胞运动性、肌动蛋白重组、肿瘤的恶性转型、侵袭转移、转录因子的调节及肿瘤的血管生成等.Ras相关的C3肉毒素底物1作为Rho家族成员之一,在肿瘤细胞的增殖分化与凋亡、细胞运动、侵袭与转移及肿瘤血管生成方面发挥重要的作用.     

Rho蛋白家族的生物活性

近年来对Rho蛋白家族的研究进展很快 ,已发现有Rho ,Rac ,Cdc42三个亚家族共十余种。这些小分子量G蛋白具有GTP酶活性 ,在细胞的信号转导通路中起重要作用。在调节细胞骨架、细胞运动、细胞增殖、细胞凋亡、细胞转录、细胞转化、恶性肿瘤细胞的浸润和转移等方面发挥重要作用。     

Differential cell-specific location of Cav-1 and Ca2+-ATPase in terminal Schwann cells and mechanoreceptive Ruffini endings in the periodontal ligament of the rat incisor

Caveolae are involved in clathrin-independent endocytosis, transcytosis, signal transduction, and tumor suppression – all of which depend on their main constituent protein caveolin families. The periodontal Ruffini ending has been reported to develop a caveola-like structure on the cell membrane of both the axon terminals and Schwann sheaths, suggesting the existence of an axon–Schwann cell interaction in the periodontal Ruffini endings. However, little information is available concerning the functional significance of these caveolae. The present study was undertaken to examine the immunolocalization of caveolin-1, -3 (Cav-1, Cav-3) and Ca²⁺-ATPase in the periodontal Ruffini endings of the rat incisor. Decalcified sections of the upper jaws were processed for immunocytochemistry at the levels of light and electron microscopy. Some immunostained sections were treated with histochemistry for nonspecific cholinesterase (nChE) activity. Observations showed the periodontal Ruffini endings were immunopositive for Cav-1, but not Cav-3. Immunoreactive products for Cav-1 were confined to caveola-like structures in the cell membranes of the cytoplasmic extensions and cell bodies of the terminal Schwann cells associated with the periodontal Ruffini endings. However, the axonal membranes of the terminals did not express any Cav-1 immunoreaction. Double staining with Ca²⁺-ATPase and either protein gene product 9.5 (PGP 9.5) or S-100 protein disclosed the co-localization of immunoreactions in the axonal branches of the periodontal Ruffini endings, but not in the terminal Schwann cells. As Ca²⁺ plays an important role in mechanotransduction, these characteristic immunolocalizations show Cav-1/Ca²⁺-ATPase might be involved in the quick elimination of intracellular Ca²⁺ in mechanotransduction.     

Caveolin-1在皮肤疾病中的研究进展

Caveolin-1(Cav-1)在疾病中的表达已成为当前的研究热点,特别是在肿瘤中的表达尤为热门。Cav-1在皮肤相关疾病中也存在表达异常,在皮肤肿瘤、结缔组织病、银屑病等恶性、难治性、复发性皮肤病发挥着重要作用。Cav-1不仅是各种增殖性和炎症性皮肤病的重要病理生理因子,而且可以作为治疗的靶点,靶向调控Cav-1可能成为皮肤科的一种新的治疗策略,现就Cav-1在皮肤相关疾病中的表达及作用机制进行综述。     

CDH 13基因的研究进展

CDH 13是一个独特的钙粘蛋白.近来的研究表明,CDH 13是一个抑癌基因,此外,它在细胞粘附、信号转导及细胞生长调节等方面也发挥着重要作用.CDH 13表达的沉默可由其基因5′启动子区的异常甲基化或等位基因的缺失与异常甲基化的联合作用导致.     

骨桥蛋白与肿瘤转移

骨桥蛋白是一种分泌型、黏附性的糖基化磷蛋白,与其主要受体整合素和CD44相互作用,参与多器官、多组织的生理病理过程,具有多种功能,如介导细胞移行、抑制钙化、调节免疫细胞功能、控制肿瘤细胞表型以及抑制凋亡等。近年来的研究揭示,骨桥蛋白在肿瘤细胞的黏附、移行、浸润、血管新生以及肿瘤的微环境中起关键作用。本文对骨桥蛋白在肿瘤中的信号转导、基因表达与调控以及肿瘤转移过程中的作用予以综述。     

Extensive vascularization of developing mouse ovaries revealed by caveolin-1 expression.

Expression screening for genes preferentially expressed in mouse fetal ovaries relative to testes identified Cav-1 as a candidate female-specific gene. Cav-1 encodes caveolin-1, a component of the cell membrane invaginations known as caveolae, which are involved in lipid regulation and signal transduction. In situ hybridization revealed high levels of Cav-1 mRNA in developing ovaries, compared with moderate or low levels in testes. Analysis of caveolin-1 protein distribution by immunofluorescence showed this difference to be due to the development of a dense and complex vascular network in the developing ovary. These observations point to a higher degree of differentiation and organization of the early stage mammalian ovary than previously suspected.     

Caveolin-1 knockout mice show an impaired angiogenic response to exogenous stimuli

Recent studies have shown that caveolin-1 (Cav-1) plays an important role as a regulator of angiogenesis in vitro. Here, we use Cav-1 knockout (KO) mice as a model system to examine the in vivo relevance of these findings. A primary mediator of angiogenesis is basic fibroblast growth factor (bFGF). Thus, we studied bFGF-induced angiogenesis in Cav-1 KO mice using a reconstituted basement membrane system, ie, Matrigel plugs, supplemented with bFGF. In Cav-1 KO mice, implanted Matrigel plugs showed a dramatic reduction in both vessel infiltration and density, as compared with identical plugs implanted in wild-type control mice. We also examined the necessity of Cav-1 to support the angiogenic response of an exogenous tumor by subcutaneously injecting Cav-1 KO mice with the melanoma cell line, B16-F10. We show that tumor weight, volume, and vessel density are all reduced in Cav-1 KO mice, consistent with diminished angiogenesis. Ultrastructural analysis of newly formed capillaries within the exogenous tumors reveals a lack of endothelial caveolae and incomplete capillary formation in Cav-1 KO mice. These results provide novel evidence that Cav-1 and caveolae play an important positive role in the process of pathological angiogenesis in vivo.     

B-RAF基因和肿瘤

B-RAF基因在肿瘤细胞增殖、分化和凋亡等方面发挥重要作用。本文就B-RAF基因作为RAF-MEK-ERK信号转导通路中的重要成员在肿瘤中的作用进行阐述。     

Redox regulation of human thioredoxin network

Oxidative stresses are largely mediated by intracellular protein oxidations by reactive oxygen species (ROS). Host cells are equipped with antioxidants that scavenge ROS. The cellular reduction/oxidation (redox) balance is maintained by ROS and antioxidants. Accumulating evidence suggests that the redox balance plays an important role in cellular signaling through the redox modification of cysteine residues in various important components of the signal transduction pathway. Thioredoxin (TRX) is a small protein playing important roles in cellular responses, including cell growth, cell cycle, gene expression, and apoptosis, to maintain the redox circumstance. Moreover, many recent papers have shown that the redox regulation by TRX is deeply involved in the pathogenesis of various oxidative stress-associated disorders. This review focuses on TRX and its related molecules, and discusses the role of TRX-dependent redox regulation in oxidative stress-induced signal transduction.     

Rho GTPases与肿瘤侵袭转移相关性的研究进展

Rho GTPases属小分子量GTPases,作为信号传导通路中重要的“分子开关”,调控细胞形态、骨架重建、迁移及细胞周期与凋亡等诸多过程.近来的研究表明,Rho GTPases家族成员在多种恶性肿瘤中异常表达,并通过调控上皮细胞极性丧失、细胞-细胞间的连接及黏附、细胞骨架重组和迁移运动、细胞外基质的重塑、细胞进入血管淋巴管的能力等方面参与肿瘤细胞的侵袭转移.深入研究Rho GTPases在肿瘤侵袭转移中的作用意义重大,Rho GT-Pases将有望成为判断肿瘤侵袭转移性发展的新指标,并为肿瘤治疗提供新靶点、新方向.