• Molecules and Cells
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• 제27권6호
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• pp.629-634
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• 2009

G protein-coupled receptors (GPCRs) are part of multi-protein networks called 'receptosomes'. These GPCR interacting proteins (GIPs) in the receptosomes control the targeting, trafficking and signaling of GPCRs. PDZ domain proteins constitute the largest protein family among the GIPs, and the predominant function of the PDZ domain proteins is to assemble signaling pathway components into close proximity by recognition of the last four C-terminal amino acids of GPCRs. We present here a machine learning based approach for the identification of GPCR-binding PDZ domain proteins. In order to characterize the network of interactions between amino acid residues that contribute to the stability of the PDZ domain-ligand complex and to encode the complex into a feature vector, amino acid contact matrices and physicochemical distance matrix were constructed and adopted. This novel machine learning based method displayed high performance for the identification of PDZ domain-ligand interactions and allowed the identification of novel GPCR-PDZ domain protein interactions.

• Molecules and Cells
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• 제38권10호
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• pp.836-842
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• 2015

G protein-coupled receptors (GPCRs) constitute the largest and the most physiologically important membrane protein family that recognizes a variety of environmental stimuli, and are drug targets in the treatment of numerous diseases. Recent progress on GPCR structural studies shed light on molecular mechanisms of GPCR ligand recognition, activation and allosteric modulation, as well as structural basis of GPCR dimerization. In this review, we will discuss the structural features of GPCRs and structural insights of different aspects of GPCR biological functions.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• Tuberculosis and Respiratory Diseases
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• 제55권1호
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• pp.21-30
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• 2003

서 론 : MUC genes의 증가와 배상세포의 증식 기전에 성장인자(growth factor)인 상피세포 성장인자 및 수용체(epidermal growth factor receptor; EGFR)가 배상세포의 증식이나 이형성에 관여한다. EGFR의 ligands 중의 한 종류인 heparin binding EGF(HB-EGF)는 세포막에 존재하는 pro-heparin binding EGF(pro-HB-EGF)로부터 유리된다. HB-EGF의 유리는 G-protein과 연관이 있다. 따라서, 본 연구는 그람 음성세균의 lipopolysaccande(LPS)에 의한 기도 점액 과생성의 기전을 밝히고, 기도점액 과분비에서 EGFR과 G-protein의 연관성을 밝혀 기도 점액 과분비 기전을 밝히고자 한다. 연구방법 : NCI-H292 세포배양에서 LPS단독 투여 또는TGF-${\alpha}$와 병합 투여한 후 MUC5AC의 당단백질을 ELISA법으로 측정하였다. LPS에 의한 MUC5AC 당단백질의 생성 기전을 밝히기 위해서 heterotrimeric G-protein 억제제인 mastoparan을 투여하고 TNF-${\alpha}$와 MUC5AC를 ELISA법으로 각각 측정하였다. MUC5AC의 생성에서 G-protein과 EGFR의 연관성을 확인하기 위하여 EGFR이 항상 발현되어 있고 MUC5AC를 분비할 수 있는 NCI-H292 세포에 G-protein 자극제인 mastoparan-7로 자극한 후 MUC5AC의 생성을 측정하였다. G-protein이 활성화하여 metalloproteinase가 세포막에 있는 HB-EGF를 유리하여 EGFR이 활성화하여 MUC5AC가 생성여부를 확인하기 위하여 ADAM10으로 NCI-H292세포에 자극하여 MUC5AC의 생성을 측정하였다. MUC5AC 생성이 EGFR과 연관성을 확인하기 위하여 특이 EGFR tyrosine kinase 억제제인 AG1478과 중화 polyclonal EGF 항체를 전처치 후 MUC5AC를 측정하였다. 결 과 : LPS의 자극에 의한 MUC5AC의 생성은 LPS 농도에 유의하게 증가 되지 않았으나, EGFR의 ligand인 TGF-${\alpha}$를 동시 투여한 경우는 LPS의 농도에 비례하여 유의하게 증가하였다. LPS의 자극은 TNF-${\alpha}$의 생성을 유의하게 증가시켰으며, G-protein 억제제인 mastoparan을 전처치한 경우는 TNF-${\alpha}$가 유의하게 감소 되었다. LPS 자극 전에 TNF-${\alpha}$ antibody, AG1478 또는 mastoparan을 전처치한 경우는 MUC5AC의 생성이 유의하게 억제되었다. MUC5AC의 생생에서 G-protein과 EGFR의 연관성에 대한 실험에서 MUC5AC의 생성이 mastoparan-7의 농도에 따라 유의하게 증가되었으며, EGF의 중화항체를 사용한 경우는 MUC5AC의 생성이 감소되었다. 또한 Matrix metalloproteinase인 ADAM10의 농도에 비례하여 MUC5AC의 생성을 증가시켰다. 결 론 : LPS에 의한 MUC5AC의 분비는 LPS가 TNF-${\alpha}$를 생성시키고, TNF-${\alpha}$가 EGFR의 발현을 유도하여 MUC5AC가 분비되었다. 또한 MUC5AC의 생성에 있어서 G-protein의 활성은 matrix metalloproteinase에 의하여 EGFR의 ligand 인 HB-EGF가 유리되어 EGFR의 transacti vation으로 MUC5AC가 생성되는 것으로 사료된다.

• Interdisciplinary Bio Central
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• 제5권3호
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• pp.6.1-6.7
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• 2013

Many insects such as mosquitoes cause life-threatening diseases such as malaria, yellow fever and West Nile virus. Malaria alone infects 500 million people annually and causes 1-3 million death per year. Volatile insect repellents, which are detected through the sense of smell, have long been used to protect humans against insect pests. Antifeed-ants are non-volatile aversive compounds that are detected through the sense of taste and prevent insects from feeding on plants. The molecular targets and signaling path-ways required for sensing insect repellents and antifeedants are poorly understood. Transient Receptor Potential (TRP) Ca2+-permeable cation channels exist in organisms ranging from C. elegans to D. melanogaster and Homo sapiens. Drosophila has 13 family members, which mainly function in sensory physiology such as vision, thermotaxis and chemotaxis. G protein-coupled receptors (GPCRs) initiate olfactory signaling cascades in mammals and in nematodes C.elegans. However, the mechanisms of G protein signaling cascades in insect chemosensation are controversial. In this review, I will discuss the putative roles of G protein-coupled receptors (GPCRs) and Transient Receptor Potential (TRP) channels as targets for insect repellents.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.82-87
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• 1994

Signal transduction through G protein-coupled receptors comprises three functional components, a receptor, a G protcin and a effector protein. Work over the last sevcral ycars has led to the characterization or virtually all of the components or these systems. what has come out or those studies is that these mechanisms of signal transduction are pervasive in nature being found in mammalian and avian species, as well as lower organisms such as yeast and slime mold. It is known that G protein-coupled receptors mediate the action of such diverse molecules such as small hormones and neurotransmitters, small peptide molecules as well as glycoprotein hormones and various sensory perceptions such as light, olfaction and most likely taste.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.104.2-104.2
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• 2006

• 유전체소식지
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• 제3권3호
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• pp.8-10
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• 2003

• Animal cells and systems
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• 제2권4호
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• pp.471-476
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• 1998

The G protein-activated inwardly rectifying $K^＋$ channel (GIRK1) was coex-pressed in Xenopus oocytes along with the $5-HT_{1A}$ receptor, a 7-helix receptor known to be coupled to $K^＋$ channels in many neural tissues. Thus, the activation of the $5-HT_{1A}$ receptor by its agonist leads to the opening of GIRK1. The GIRK1 current was measured using the two electrode voltage clamp technique with bath application of 5-HT in the presence of various external potassium concentrations $[K^＋]_0$. GIRK1 showed a strong inward rectification since only hyperpolarizing voltages evoked inward currents. $K^{+}$ was the major ion carrier as evidenced by about 44㎷ voltage shift corresponding to a 10-fold external 〔$K^＋$〕 change. 5-HT induced a concentration-dependent inward $K^＋$ current ($EC_{50}{\equation omitted}10.7nM$) which was blocked by $Ba^{2＋}$. Pertussis toxin (PTX) pre-treatment reduced the $K^＋$ current by as much as about 70%, suggesting that PTX-sensitive G protein ($G_i or G_o$ type) are involved in the $5-HT_{1A}$ receptor-GIRK1 coupling in Xenopus oocytes.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.101-108
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• 2018

G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as b-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.