胰岛素受体介导的信号传递

就胰岛素与其受体结合后, 信号传递的过程及参与信号传递的细胞内信号分子进行了综述.胰岛素作为一种重要激素,参与机体的新陈代谢, 调节细胞的生长分化.其发挥生理功能的第一步是与靶细胞膜上的受体相结合, 激活胰岛素受体的酪氨酸激酶活性, 随之磷酸化细胞内的信号分子, 从而使胰岛素的刺激信号转化为细胞反应.     

磷脂酰肌醇3激酶与胰岛素抵抗

胰岛素(Insulin,INS)通过胰岛素信号转导途径发挥其促进合成代谢、稳定血糖的生理作用,磷脂酰肌醇-3激酶(phos-phatidylinositol-3-kinase,PI-3K)是胰岛素信号转导中的关键分子.PI-3K是由催化和调节亚基构成的异源二聚体.催化和调节亚基在数量上保持平衡,此平衡的紊乱可以改变PI-3K的活性.研究表明调节亚基p85α与胰岛素的敏感性成负相关,动物和人胰岛素抵抗(Insulin resistance,IR)发生调节亚基p85α的过度表达.     

细胞内信号传递与转录调控的研究进展

综合近年来有关细胞内信号传递与转录调控的研究进展,总结出３个细胞内信号传递系统－ＭＡＰ激酶途径、ＪＡＫ／ＳＴＡＴ途径和ＮＫ－ｋＢ途径,细胞外信号分别通过以上３种途径,在细胞核、细胞膜、细胞浆中激活转录因子,调控基因表达,其中可逆性磷酸化对转录因子活性的调节起着重要的作用。     

幽门螺杆菌通过激活磷脂酰肌醇3-激酶信号来调节细胞迁移

目的幽门螺杆菌被认为是诱发胃癌的最强的风险因素。幽门螺旋杆菌的毒性成分是可以增加癌症危险的cag分泌系统,它可以使cagA和肽聚糖易位进入宿主细胞,进而激活信号转导通路。AKT是磷脂酰肌醇3。激酶（PI3K）的目的蛋白,并在胃癌中被激活,但PI3K-AKT和具有潜在致癌性的幽门螺旋杆菌诱导的细胞反应之间的关系尚不清楚。方法我们揭示了介导幽门螺旋杆菌刺激的AKT活化和胃上皮细胞的这些生物学结果之间的分子通路。结果幽门螺旋杆菌以Scr和表皮生长因子受体依赖性方式增加PI3K-AKT的信号,是幽门螺旋杆菌诱导的细胞迁移不可或缺的。结论这些结果表明,PI3K-AKT信号调节幽门螺旋杆菌诱发的病理生理反应,从而降低癌变门槛。     

胰岛素样生长因子-1对血管平滑肌细胞PI3K/PTEN信号通路的影响

目的:探讨胰岛素样生长因子-1(IGF-1)促血管平滑肌细胞(VSMC)增殖的细胞内信号转导机制.方法:体外培养的兔血管平滑肌细胞分3组处理,以细胞计数、噻唑盐比色法测定细胞增殖能力,以磷脂酰肌醇-3激酶(PI3K)特异性抑制剂渥漫青霉素(WT)孵育细胞间接反映PI3K作用.Western Blot定量磷酸酶PTEN表达水平,免疫沉淀、特异底物diC16PIP3绿色试剂法测定PTEN脂质磷酸酶活性.结果:IGF-1(100 μg/L)使细胞计数及MTT 比色A值分别增加至对照组的2.8倍和3.8倍,WT抑制VSMC增殖,并完全逆转IGF-1的作用(均P<0.01).各浓度IGF-1对PTEN蛋白表达水平无明显影响,其对PTEN活性的抑制呈浓度(10～100 μg/L)及时间(3 min～24 h)依赖性(均P<0.01).结论:IGF-1促VSMC增殖作用与活化PI3K蛋白激酶的促生长活性及抑制PTEN脂质磷酸酶的负性调节细胞生长作用有关.     

蛋白激酶B及其在磷脂酰肌醇3-激酶介导的信号转导中的作用

蛋白激酶Ｂ（ＰＫＢ）是原癌基因ｃ－ａｋｔ的表达产物,它参与由生长因子激活的经磷脂磷肌醇３－激酶（ＰＩ３Ｋ）介导的信号转导过程。与许多蛋白激酶相似,ＰＫＢ分子具有一特殊的ＡＨ／ＰＨ结构域（ＡＨ／ＰＨｄｏｍａｉｎ）,后者能介导信号分子间的相互作用。ＰＫＢ是ＰＩ３Ｋ直接的靶蛋白。ＰＩ３Ｋ产生的脂类第二信使ＰＩ－３,４,Ｐ２和ＰＩ－３,４,５－Ｐ３等均能与ＰＫＢ和磷酸肌醇依赖性蛋白激酶（ＰＤＫ）的ＡＨ／Ｐ     

磷脂酰肌醇—3激酶／蛋白激酶B信号系统

质膜民分磷脂酰肌醇被其３位激酶（ＰＩ３Ｋ）活化后,可以使蛋白激酶Ｂ（ＰＫＢ）由细胞浆定位于胞膜,继而被磷酸化激活。ＰＫＢ是原癌基因ａｋｔ的产物,具有丝／苏氨酸蛋白激酶活性,介导细胞代谢、生长、增殖等效应。ＰＩ３／ＰＫＢ系统是近年来发现的一个生长因子信号转导通路。     

由胰岛素调控PI3激酶引发的果蝇滞育的自然变异

Williams等人的研究把果蝇在越冬策略及滞育方面的自然变异与由胰岛素调控的磷脂酰肌醇3-激酶（PI3-激酶）基因-Dp110联系在了一起。通过运用Dp110删除和转基因果蝇中的基因组学补救片断的方法，结果表明，滞育而引起的生殖停滞，与Dp110基因有关。Dp110基因的删除增加了滞育个体的比例，然而，Dp110基因在不包括视觉系统的神经系统中的表达却能减少滞育个体的比例。     

胰岛素受体底物活性调控的分子机制

胰岛素受体底物(insulin receptor substrate,IRS)是胰岛素信号转导通路中一个极其重要的信号分子,对胰岛素信号级联效应具有至关重要的作用。目前有关胰岛素受体底物活性调节的研究主要集中在两个方面,一方面是磷酸化水平的调节机制,另一方面是细胞因子信号阻抑剂(suppressor of cytokine signaling,COCS)所介导的直接和间接调控。了解胰岛素受体底物活性调节机制将有助于进一步探索胰岛素抵抗和Ⅱ型糖尿病的发病机制。     

Signal transduction in the erythropoietin receptor system

Events relayed via the single transmembrane receptor for erythropoietin (Epo) are essential for the development of committed erythroid progenitor cells beyond the colony-forming unit-erythroid stage, and this clearly involves Epo's inhibition of programmed cell death (PCD). Less well resolved, however, are issues regarding the precise nature of Epo-dependent antiapoptotic mechanisms, the extent to which Epo might also promote mitogenesis and/or terminal erythroid differentiation, and the essential vs modulatory nature of certain Epo receptor cytoplasmic subdomains, signal transducing factors, and downstream pathways. Accordingly, this review focuses on the following aspects of Epo signal transduction: (1) Epo receptor/Jak2 activation mechanisms; (2) the critical vs dispensable nature of (P)Y sites and SH2 domain-encoding effectors in survival, growth, and differentiation responses; (3) primary mechanisms by which Epo inhibits PCD; (4) the integration of signals relayed by coexpressed and possibly directly interacting cytokine receptors; and (5) predictions regarding effector function which are provided by the association of certain primary and familial polycythemias with mutated human Epo receptor forms.     

Signal transduction via the growth hormone receptor

Rapid progress has been made recently in the definition of growth hormone (GH) receptor signal transduction pathways. It is now apparent that many cytokines, including GH, share identical or similar signalling components to exert their cellular effects. This review provides a brief discourse on the signal transduction pathways, which have been demonstrated to be utilized by GH. The identification of such pathways provides a basis for understanding the pleiotropic actions of GH. The mechanisms by which the specific cellular effects of GH are achieved remain to be elucidated.     

Signal transduction through the T-cell antigen receptor.

The mechanism by which ligand binding to the T-cell antigen receptor triggers the T-cell activation program has long been one of the most fascinating questions in lymphocyte biology. Here, we review recent insights into the transmembrane signaling functions of this multisubunit receptor complex.     

基瘦蛋白与其受体介导的信号转导

瘦蛋白是由肥胖基因编码的一种16kDa的活性蛋白质,其三维结构与长链细胞因子家族相似。瘦蛋白受体属I类细胞因子受体家族,包括6种剪接体（OB-Ra、b、c、d、e、f）,广泛分布于中枢及外周组织,其中的功能性受体（OB-Rb）与瘦蛋白结合后可激活Janus激酶/信号转导及转录激活蛋白（JAK-STAT）途径、原活化的蛋白激酶（MAPK）途径、磷脂酰肌醇-3-激酶（PI3K）/磷酸二酯酶3B（PDE3B）/cAMP途径、5＇-AMP活化的蛋白激酶（AMPK）等主要信号途径,在调节能量代谢、神经内分泌和免疫反应等方面发挥多效能作用,并参与肥胖、糖尿病、自身免疫性疾病等的发生发展过程。该文主要结合瘦蛋白及其受体的结构和功能对二者相互作用的模式和信号通路作一综述。     

Rin1 regulates insulin receptor signal transduction pathways

Rin1 is a multifunctional protein containing several domains, including Ras binding and Rab5 GEF domains. The role of Rin1 in insulin receptor internalization and signaling was examined by expressing Rin1 and deletion mutants in cells utilizing a retrovirus system. Here, we show that insulin-receptor-mediated endocystosis and fluid phase insulin-stimulated endocytosis are enhanced in cells expressing the Rin1:wild type and the Rin1:C deletion mutant, which contain both the Rab5-GEF and GTP-bound Ras binding domains. However, the Rin1:N deletion mutant, which contains both the SH2 and proline-rich domains, blocked insulin-stimulated receptor-mediated and insulin-stimulated fluid phase endocytosis. In addition, the expression of Rin1:delta (429-490), a natural occurring splice variant, also blocked both receptor-mediated and fluid phase endocystosis. Furthermore, association of the Rin1 SH2 domain with the insulin receptor was dependent on tyrosine phosphorylation of the insulin receptor. Morphological analysis indicates that Rin1 co-localizes with insulin receptor both at the cell surface and in endosomes upon insulin stimulation. Interestingly, the expression of Rin1:wild type and both deletion mutants blocks the activation of Erk1/2 and Akt1 kinase activities without affecting either JN or p38 kinase activities. DNA synthesis and Elk-1 activation are also altered by the expression of Rin1:wild type and the Rin1:C deletion mutant. In contrast, the expression of Rin1:delta stimulates both Erk1/2 and Akt1 activation, DNA synthesis and Elk-1 activation. These results demonstrate that Rin1 plays an important role in both insulin receptor membrane trafficking and signaling.