gpDB: a database of GPCRs, G-proteins, effectors and their interactions

Theodoropoulou, Margarita C.; Bagos, Pantelis G.; Spyropoulos, Ioannis C.; Hamodrakas, Stavros J.

doi:10.1093/bioinformatics/btn206

Cited by 29 publications

(25 citation statements)

References 14 publications

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“…The SULP-induced perturbation of the aforementioned signaling pathways might also be a result of off-target drug effects, including interactions of SULP with G protein-coupled receptors, a hypothesis that likely merits further investigation (Kristiansen, 2004;Theodoropoulou et al, 2008). In conclusion, the present data indicate several possible mechanisms that might play roles in the down-regulation of CYP3A, CYP2C, and CYP2D by SULP.…”

Section: Discussionmentioning

confidence: 63%

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

et al. 2012

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Various hormonal and monoaminergic systems play determinant roles in the regulation of several cytochromes P450 (P450s) in the liver. Growth hormone (GH), prolactin, and insulin are involved in P450 regulation, and their release is under dopaminergic control. This study focused on the role of D 2 -dopaminergic systems in the regulation of the major drug-metabolizing P450s, i.e., CYP3A, CYP2C, and CYP2D. Blockade of D 2 -dopaminergic receptors with either sulpiride (SULP) or 4-(4-chlorophenyl)-1-(1H-indol-3-ylmethyl)piperidin-4-ol (L-741,626) markedly down-regulated CYP3A1/2, CYP2C11, and CYP2D1 expression in rat liver. This suppressive effect appeared to be mediated by the insulin/ phosphatidylinositol 3-kinase/Akt/FOXO1 signaling pathway. Furthermore, inactivation of the GH/STAT5b signaling pathway appeared to play a role in D 2 -dopaminergic receptor-mediated down-regulating effects on these P450s. SULP suppressed plasma GH levels, with subsequently reduced activation of STAT5b, which is the major GH pulse-activated transcription factor and has up-regulating effects on various P450s in hepatic tissue. Levels of prolactin, which exerts down-regulating control on P450s, were increased by SULP, which may contribute to SULP-mediated effects. Finally, it appears that SULP-induced inactivation of the cAMP/protein kinase A/cAMP-response element-binding protein signaling pathway, which is a critical regulator of pregnane X receptor and hepatocyte nuclear factor 1␣, and inactivation of the c-Jun N-terminal kinase contribute to SULP-induced down-regulation of the aforementioned P450s. Taken together, the present data provide evidence that drugs acting as D 2 -dopaminergic receptor antagonists might interfere with several major signaling pathways involved in the regulation of CYP3A, CYP2C, and CYP2D, which are critical enzymes in drug metabolism, thus affecting the effectiveness of the majority of prescribed drugs and the toxicity and carcinogenic potency of a plethora of toxicants and carcinogens.

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Section: Discussionmentioning

confidence: 63%

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

et al. 2012

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“…The interaction between GPCRs and GIPs creates larger GPCR-associated protein complexes, placing the GPCRs at the center of protein networks that participate in the dynamic regulation of the receptor (Daulat et al 2009;Ritter and Hall 2009). GIPs databases and servers deal with Gproteins (Elefsinioti et al 2004;Satagopam et al 2010;Theodoropoulou et al 2008) and PDZ domains (Beuming et al 2005), and these are summarized in Table 9.4 and described below.…”

Section: Intracellular Partners and Signaling Pathwaysmentioning

confidence: 99%

“…In addition, the Gprotein's subunits activate or inhibit a variety of effector proteins that modulate the cellular signal-transduction functions (Bosier and Hermans 2007;Wettschureck and Offermanns 2005). Two databases are available for G-protein complexes: the general gpDB (Elefsinioti et al 2004;Theodoropoulou et al 2008) and the more recent Human-gpDB (Satagopam et al 2010). Both provide information on the coupling between GPCR and G-protein ' subunit and on the interactions between the G-protein subunits and different effectors, and supply additional information on the interacting partners.…”

Section: Intracellular Partners and Signaling Pathwaysmentioning

confidence: 99%

GPCR & Company: Databases and Servers for GPCRs and Interacting Partners

Kowalsman

Niv

2013

Advances in Experimental Medicine and Biology

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G-protein-coupled receptors (GPCRs) are a large superfamily of membrane receptors that are involved in a wide range of signaling pathways. To fulfill their tasks, GPCRs interact with a variety of partners, including small molecules, lipids and proteins. They are accompanied by different proteins during all phases of their life cycle. Therefore, GPCR interactions with their partners are of great interest in basic cell-signaling research and in drug discovery.Due to the rapid development of computers and internet communication, knowledge and data can be easily shared within the worldwide research community via freely available databases and servers. These provide an abundance of biological, chemical and pharmacological information.This chapter describes the available web resources for investigating GPCR interactions. We review about 40 freely available databases and servers, and provide a few sentences about the essence and the data they supply. For simplification, the databases and servers were grouped under the following topics: general GPCR-ligand interactions; particular families of GPCRs and their ligands; GPCR oligomerization; GPCR interactions with intracellular partners; and structural information on GPCRs. In conclusion, a multitude of useful tools are currently available. Summary tables are provided to ease navigation between the numerous and partially overlapping resources. Suggestions for future enhancements of the online tools include the addition of links from general to specialized databases and enabling usage of user-supplied template for GPCR structural modeling.

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“…To construct high-quality benchmark dataset, primary sequences of GPCRs and G proteins are collected from the database of GPCRs, G proteins, effectors and their interactions (gpDB) at http://biophysics.biol.uoa.gr/gpDB/ (Elefsinioti et al 2004;Theodoropoulou et al 2008). The gpDB is a publicly accessible database that collects and combines information about GPCRs and G proteins, as well as information concerning known coupling specificity between these proteins.…”

Section: Data Collection and Dataset Constructionmentioning

confidence: 99%

“…The dissociated a-subunit can activate or inhibit several effector proteins, such as adenylyl cyclase 1-9, PLCb 1-4, tyrosine kinases, phosphodiesterases, phosphoinositide 3-kinase, ion channels and molecules of the mitogen-activated protein kinase pathway, resulting in a variety of cellular functions and physiological responses that depend on the biological specificity of the dissociated subunits (Cabrere-Vera et al 2003;Elefsinioti et al 2004;Pierce et al 2002;Sgourakis et al 2005b;Theodoropoulou et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Classification of G proteins and prediction of GPCRs-G proteins coupling specificity using continuous wavelet transform and information theory

Zhou²,

Dai³

et al. 2011

Amino Acids

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The coupling between G protein-coupled receptors (GPCRs) and guanine nucleotide-binding proteins (G proteins) regulates various signal transductions from extracellular space into the cell. However, the coupling mechanism between GPCRs and G proteins is still unknown, and experimental determination of their coupling specificity and function is both expensive and time consuming. Therefore, it is significant to develop a theoretical method to predict the coupling specificity between GPCRs and G proteins as well as their function using their primary sequences. In this study, a novel four-layer predictor (GPCRsG_CWTIT) based on support vector machine (SVM), continuous wavelet transform (CWT) and information theory (IT) is developed to classify G proteins and predict the coupling specificity between GPCRs and G proteins. SVM is used for construction of models. CWT and IT are used to characterize the primary structure of protein. Performance of GPCRsG_CWTIT is evaluated with cross-validation test on various working dataset. The overall accuracy of the G proteins at the levels of class and family is 98.23 and 85.42%, respectively. The accuracy of the coupling specificity prediction varies from 74.60 to 94.30%. These results indicate that the proposed predictor is an effective and feasible tool to predict the coupling specificity between GPCRs and G proteins as well as their functions using only the protein full sequence. The establishment of such an accurate prediction method will facilitate drug discovery by improving the ability to identify and predict protein-protein interactions. GPCRsG_CWTIT and dataset can be acquired freely on request from the authors.

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gpDB: a database of GPCRs, G-proteins, effectors and their interactions

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 29 publications

References 14 publications

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

GPCR & Company: Databases and Servers for GPCRs and Interacting Partners

Classification of G proteins and prediction of GPCRs-G proteins coupling specificity using continuous wavelet transform and information theory

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gpDB: a database of GPCRs, G-proteins, effectors and their interactions

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 29 publications

References 14 publications

D2-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D2-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

GPCR & Company: Databases and Servers for GPCRs and Interacting Partners

Classification of G proteins and prediction of GPCRs-G proteins coupling specificity using continuous wavelet transform and information theory

Contact Info

Product

Resources

About

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D

D₂-Dopaminergic Receptor-Linked Pathways: Critical Regulators of CYP3A, CYP2C, and CYP2D