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Predicting the Coupling Specificity of g-protein Coupled Receptors to g-proteins by Support Vector Machines

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genomics, Proteomics & Bioinformatics 2005年第4期3卷 247-251页

作者： Cui-Ping guan Zhen-Ran Jiang Yan-Hong Zhou Hubei Bioinformatics and Molecular Imaging Key Laboratory Huazhong University of Science and Technology Wuhan 430074 China.

g-protein coupled receptors （gPCRs） represent one of the most important classes of drug targets for pharmaceutical industry and play important roles in cellular signal transduction. Predicting the coupling specificity of gPCRs to g-proteins is vital for further understanding the mechanism of signal transduction and the function of the receptors within a cell, which can provide new clues for pharmaceutical research and development. In this study, the features of amino acid compositions and physiochemical properties of the full-length gPCR sequences have been analyzed and extracted. Based on these features, classifiers have been developed to predict the coupling specificity of gPCRs to g-protelns using support vector machines. The testing results show that this method could obtain better prediction accuracy.

关键词： gPCR g-protein SVM coupling specificity

genetic predisposition to essential hypertension in a Mongolian population Detecting the C825T polymorphism of the g-protein beta 3 subunit gene

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Neural Regeneration Research 2007年第3期2卷 146-150页

作者： Chunyu Zhang Shigang Zhao guangming Niu Rile Hu Zhiguang Wang Mingfang Jiang Department of Neurology First Affiliated Hospital of Inner Mongolia Medical College Hohhot 010050 Nei Monggol Autonomous Region China Department of Imaging First Affiliated Hospital of Inner Mongolia Medical College Hohhot 010050 Nei Monggol Autonomous Region China Wulate Houqi Red Cross Society Wulate Houqi 015500 Nei Monggol Autonomous Region China

BACKgROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful for prevention to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between C825T polymorphisms of g-protein beta 3 subunit gene （gNB3）, the important candidate gene of various disease of cardiovascular system, and Mongolian patients with essential hypertension. DESIgN： A comparative observation. SETTINgS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： Totally 267 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia. The patients were screened based on the diagnostic standard of hypertension set by WHO in 1999, and the enrolled subjects were divided into two groups according to the level of blood pressure： ① Normal blood pressure group （n =124）： 64 males and 60 females, systolic blood pressure （SBP）〈 140 mm Hg （1 mm Hg=0.133 kPa）, diastolic blood pressure （DBP）〈 90 mm Hg;②Essential hypertension group （n =143）： 71 males and 72 females, including 60 patients with simple high SBP （SBP ranged 145 to 195 mm Hg, whereas DBP 〈 90 mm Hg）. METHODS： Peripheral venous blood （5 mL） was drawn from all the subjects, the genome DNA was extracted, and the polymorphisms of the gNB3 C825T genotype were detected with the Sequenom system. Polyrnerase chain reaction （PCR） experiment and SNP detection were performed in Beijing Huada gene laboratory. Then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CI） were calculated. MAIN OUTCOME MEASURES： The di

关键词： g-protein genes mongoloid race hypertension

Pathogenicity Assay for Cochliobolus heterostrophusg-protein and MAPK Signaling Deficiency Strains

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American Journal of Plant Sciences 2014年第9期5卷 1318-1328页

作者： Ofir Degani Tel-Hai College Tel-Hai Israel Migal-galilee Research Institute Kiryat Shmona Israel

Cochliobolus heterostrophus is an agriculturally important and emerging model pathogen for studying the signaling hierarchies' role during the maize host colonization. In particular, g-protein and MAPK-linked pathways are playing a major role during pathogenesis. Although gene disruption studies are an efficient way of identifying the role of these cascades, differentiating between the mutant strains’ virulence ability may become an intricate task. For example, in C. heterostrophus, mutants in a g-protein α subunit gene, cga1, are defective in mating and appressorium formation, but unlike mutants in homologous genes in other fungal pathogens, the cga1 mutants remained highly virulent to corn under some host physiological conditions. Here, we used the cga1 strain as a model for developing an in vivo sensitive and accurate pathogenicity assay. A detailed and well controlled analysis of wild type (WT) and cga1 pathogenic behavior revealed that detached leaves are significantly more vulnerable to the disease than intact ones. In intact leaves, cga1 mutants were less infective of maize under most conditions. This difference was maximized when the first seedling leaf was chosen for inoculation and when the infected leaves, with spores or mycelia fragments droplets, were incubated for a period of four days. This optimal condition set enabled us to classify the C. heterostrophus g-protein signaling mutants deficient in α, β or both subunits in order of decreasing virulence: WT > cga1> cgb1> cga1 cgb1. The method presented proved to be accurate and sensitive enough to identify even slight variations in virulence. Moreover, it could be modified for use in studies of other foliar phytoparasitic fungi.

关键词： Cochliobolus heterostrophus g-protein Maize MAPK Signal Transduction Virulence

Isoleucine, an Essential Amino Acid, Induces the Expression of Human βDefensin 2 through the Activation of the g-protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

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Food and Nutrition Sciences 2012年第4期3卷 548-555页

作者： Youkou Konno Toshifumi Ashida Yuhei Inaba Takahiro Ito Hiroki Tanabe Atsuo Maemoto Tokiyoshi Ayabe Yusuke Mizukami Mikihiro Fujiya Yutaka Kohgo Division of gastroenterology and Hematology/Oncology Department of Medicine Asahikawa Medical University Asahikawa Japan IBD Center Sapporo Higashi Tokushukai Hospital Sapporo Japan Innate Immunity Laboratory Department of Cellular Life Science Faculty of Advanced Life Science Hokkaido University Sapporo Japan

Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or gi, a subunit of g-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the gPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of gPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.

关键词： Isoleucine Human β-Defensin g-protein Coupled Receptor Extracellular Signal-Regulated Kinases Pathway Inflammatory Bowel Disease Crohn’s Disease

New insights into sodium transport regulation in the distal nephron:Role of g-protein coupled receptors

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World Journal of Biological Chemistry 2016年第1期7卷 44-63页

作者： Luciana Morla Aurélie Edwards gilles Crambert Sorbonne Universités UPMC Univ Paris 06INSERMUniversité Paris DescartesSorbonne Paris CitéUMR_S 1138Centre de Recher-che des Cordeliers CNRS ERL 8228 Centre de Recherche des CordeliersLaboratoire de Métabolisme et Physiologie Rénale Centre de Recherche des Cordeliers INSERM U1138CNRS ERL 8228Equipe 3:Métabolisme et Physiologie Rénale

The renal handling of Na^+ balance is a major determinant of the blood pressure(BP) level. The inability of the kidney to excrete the daily load of Na+ represents the primary cause of chronic hypertension. Among the different segments that constitute the nephron, those present in the distal part(i.e., the cortical thick ascending limb, the distal convoluted tubule, the connecting and collecting tubules) play a central role in the fine-tuning of renal Na^+ excretion and are the target of many different regulatory processes that modulate Na^+ retention more or less efficiently. g-protein coupled receptors(gPCRs) are crucially involved in this regulation and could represent efficient pharmacological targets to control BP levels. In this review, we describe both classical and novel gPCR-dependent regulatory systems that have been shown to modulate renal Na^+ absorption in the distal nephron. In addition to the multiplicity of the gPCR that regulate Na^+ excretion, this review also highlights the complexity of these different pathways, and the connections between them.

关键词： Kidney Sodium excretion Blood pressure g-protein coupled receptors Peptide hormone

Mechanism of macrophage injury following traumatic hemorrhagic shock: through PTX-sensitive g-protein-mediated signal transduction pathway

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Chinese Journal of Traumatology 2002年第1期5卷 46-51页

作者：刘靖华刘良明陈惠孙胡德耀刘怀琼 Research Institute of Surgery Daping Hospital Third Military Medical University Chongqing 400042 China

Objective: To study the mechanism of macrophage injury after trauma-hemorrhagic shock. Methods: Wistar male rats underwent trauma (closed bone fracture) and hemorrhage (mean arterial blood pressure of 35 mm Hg±5 mm Hg for 60 minutes, following fluid resuscitation). Rats without trauma, hemorrhage or fluid resuscitation served as controls. Peritoneal macrophages were harvested at 6 hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the effects of pertussis toxin (PTX, as a specific inhibitor to giα) and cholera toxin (CTX, as a stimulant to gsα) on macrophage-Ia expression and TNF-α production and levels of giα and gsα. Results: The macrophages from the injured rats revealed a significant decrease of Ia positive number and TNF-α release in response to LPS. With pretreatment with PTX 10-100 ng/ml Ia positive cells and LPS-induced TNFα production in both control and impaired macrophages populations were dose-dependently increased. Both macrophages populations were not responding to CTX treatment (10-100 ng/ml). Western blot analyses showed that the levels of giα protein expression increased as much as 116.5%- 148.8% of the control level from 6 hours through 7 days after traumatic hemorrhage. The levels of gsα protein expression were reduced at 6 hours and decreased to the lowest degree; 36% of the control at day 1, began to return at day 2 and returned to the normal level at day 7, following traumatic hemorrhagic ***: PTX-sensitive g-protein may participate in the modulation of macrophage-Ia expression and TNF-α release following traumatic hemorrhagic shock. Analyses of the alteration of giα and gsα protein expressions further supports the concept that g-protein is involved in trauma-induced macrophage signal transduction pathways.

关键词： Wounds and injury Shock, hemorrhagic Macrophages g-protein

g protein and MAPK signaling pathways control the ability of Cochliobolus heterostrophusto exploit different carbon sources

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Advances in Biological Chemistry 2014年第1期4卷 40-50页

作者： Ofir Degani Tel-Hai College Upper Galilee Israel

Phytopathogenic fungi are heterotrophic organisms that excrete a complex array of enzymes for digestion of plant host tissues. Regulation and coordination of extracellular enzyme production, according to growth conditions and fungus nutritional needs, may be controlled by conserved eukaryotic signaling elements such as g-protein subunits and mitogen-activated protein kinase (MAPK). These pathways are known to mediate a complex set of responses in fungi involved in development, reproduction and pathogenicity. Here, we used a series of mutants, deficient in g-protein α (cga1) or/and β subunits or in MAPK, to test their contribution to the ability of Cochliobolus heterostrophus to utilize different carbon sources. In saprophytic culture, the g-protein α subunit mutant strains had WT levels of cellulase, pectinase and protease degradation activities, but it grew significantly slower on minimal medium containing maltose. This weakened ability implies an essential role of the CgA1 signaling in some poor nutritional environments. Remarkably, the MAPK null mutant failed to achieve the WT (and cga1) growth rate on cellulose as a sole carbon and did not grow at all for the first seven days of culture. An enzymatic activity test revealed that this strain significantly reduced cellulose extracellular degradation activity when grew on this medium. Deficiency in the MAPK encoding gene also led to reduced ability to grow on pectin, protein sources and maltose as a sole carbon. The evidence presented indicates a significant and nutrient-specific role of the g-protein and MAPK pathways in mediating growth of this fungus in different environments.

关键词： Cochliobolus Carbon Sources Extracellular Enzymes g-protein MAPK Plant Pathogen

g蛋白信号通路调节蛋白5抑制肺癌细胞生长和增强X射线照射作用及其分子机制

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中华放射医学与防护杂志 2014年第11期34卷 803-808页

作者：徐祖敏王谨左瑜芳余忠华彭芳胡晓周琦超马红莲包勇陈明中山大学附属肿瘤医院放疗科广州510080 浙江省肿瘤医院放射治疗科广东医学院附属医院肿瘤中心

目的观察g蛋白信号通路调节蛋白5（RgS5）对人肺癌细胞的作用并探索其可能的分子机制.方法采用MTT法检测过表达RgS5对人肺癌细胞系A549及Calu-3生长的影响;采用克隆形成法检测过表达RgS5及联合X射线照射对人肺癌细胞系A549及Calu-3的... 详细信息

目的观察g蛋白信号通路调节蛋白5（RgS5）对人肺癌细胞的作用并探索其可能的分子机制.方法采用MTT法检测过表达RgS5对人肺癌细胞系A549及Calu-3生长的影响;采用克隆形成法检测过表达RgS5及联合X射线照射对人肺癌细胞系A549及Calu-3的存活的影响;采用Western blot法检测凋亡相关蛋白的表达.结果过表达RgS5可显著地降低人肺癌细胞系A549及Calu-3的生长,pTriEX-RgS5组在受照后48和72 h时A549、Calu-3细胞的生长抑制率分别为44.4％（F=29.18,P＜0.05）和39.27％（F =23.04,P＜0.05）、54.3％（F=103.45,P＜0.05）和44.7％（F=108.02,P＜0.05）.RgS5可诱导肺癌细胞的凋亡,对照组、pTRiEX组及pTRiEX-RgS5组处理36 h后,A549、Calu-3细胞的凋亡率分别为（1.3±0.2）％、（3.4±0.6）％、（19.6±2.3）％（F=86.62,P＜0.05）和（3.2±0.8）％、（3.0±0.9）％、（12.8±1.8）％（F=28.80,P＜0.05）.此外,过表达RgS5与X射线照射联合,可以显著地增强抑制肺癌细胞的存活能力.结论 RgS5可显著地抑制人肺癌细胞的生长,并且过表达RgS5可增强X射线照射对肺癌细胞的杀伤作用.

关键词： g蛋白信号通路调节蛋白5 肺癌细胞凋亡放射治疗 Regulator of g-protein signaling 5

Phytochrome B and AgB1 Coordinately Regulate Photomorphogenesis by Antagonistically Modulating PIF3 Stability in Arabidopsis

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Molecular Plant 2019年第2期12卷 229-247页

作者： Pengbo Xu Hongli Lian Feng Xu Ting Zhang Sheng Wang Wenxiu Wang Shasha Du Jirong Huang Hong-Quan Yang School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China School of Agriculture and Biology Shanghai Jiao Tong University Shanghai 200240 China State Key Laboratory of genetic Engineering Collaborative Innovation Center for Genetics and Development School of Life Sciences Fudan University Shanghai 200438 China Shanghai Key Laboratory of Plant Molecular Sciences College of Life Sciences Shanghai Normal University Shanghai 200234 China These authors contributed equally to this article.

Phytochrome B (phyB), the primary red light photoreceptor, promotes photomorphogenesis in Arabidopsis by interacting with the basic helix-loop-helix transcriptional factor PIF3 and inducing its phosphorylation and degradation. Heterotrimeric g proteins are known to regulate various developmental processes in plants and animals. In Arabidopsis, the g-protein β subunit AgB1 is known to repress photomorphogenesis. However, whether and how phyB and AgB1 coordinately regulate photomorphogenesis are largely unknown. Here we show that phyB physically interacts with AgB1 in a red light-dependent manner and that AgB1 interacts directly with PIF3. Moreover, we demonstrate that the AgB1-PIF3 interaction inhibits the association of PIF3 with phyB, leading to reduced phosphorylation and degradation of PIF3, whereas the phyB-AgB1 interaction represses the association of PIF3 with AgB1, resulting in enhaneed phosphorylation and degradation of PIF3. Our results suggest that phyB and AgB1 antagonistically regulate PIF3 stability by dynamically interacting with each other and PIF3. This dynamic mechanism may allow plants to balanee phyB and g-protein signaling to optimize photomorphogenesis.

关键词： Arabidopsis phytochrome B heterotrimeric g-protein β sub unit AgB1 PIF3 photomorphogenesis protein stability