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Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionicgonadotropin Receptor

  • Min, K. S.
    • Proceedings of the KSAR Conference
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    • 2000.10a
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    • pp.10-12
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$-subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$ -subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was. efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to consist of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t63I or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632-653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agonist-occupied receptors ~2- and ~17-fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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Oxidative Stress-dependent Structural and Functional Regulation of 2-cysteine Peroxiredoxins In Eukaryotes Including Plant Cells (산화 스트레스에 의존한 식물 및 진핵세포 2-시스테인 퍼록시레독신의 기능 조절)

  • Jang, Ho-Hee;Kim, Sun-Young;Lee, Sang-Yeol
    • Journal of Plant Biotechnology
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    • v.33 no.1
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    • pp.1-9
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    • 2006
  • Peroxiredoxins (Prxs) are ubiquitously distributed and play important functions in diverse cellular signaling systems. The proteins are largely classified into three groups, such as typical 2-Cys Prx, atypical 2-Cys Prx, and 1-Cys Prx, that are distinguished by their catalytic mechanisms and number of Cys residues. From the three classes of Prxs, the typical 2-Cys Prx containing the two-conserved Cys residues at its N-terminus and C-terminus catalyzes $H_2O_2$ with the use of thioredoxin (Trx) as an electron donor. During the catalytic cycle, the N-terminal Cys residue undergoes a peroxide-dependent oxidation to sulfenic acid, which can be further oxidized to sulfinic acid at the presence of high concentrations of $H_2O_2$ and a Trx system containing Trx, Trx reductase, and NADPH. The sulfinic acid form of 2-Cys Prx is reduced by the action of sulfiredoxin which requires ATP as an energy source. Under the strong oxidative or heat shock stress conditions, 2-Cys Prx in eukaryotes rapidly switches its protein structure from low-molecular-weight species to high-molecular-weight protein structures. In accordance with its structural changes, the protein concomitantly triggers functional switching from a peroxidase to a molecular chaperone, which can protect its substrate denaturation from external stress. In addition to its N-terminal active site, the C-terminal domain including 'YF-motif' of 2-Cys Prx plays a critical role in the structural changes. Therefore, the C-terminal truncated 2-Cys Prxs are not able to regulate their protein structures and highly resistant to $H_2O_2$-dependent hyperoxidation, suggesting that the reaction is guided by the peroxidatic Cys residue. Based on the results, it may be concluded that the peroxidatic Cys of 2-Cys Prx acts as an '$H_2O_2$-sensor' in the cells. The oxidative stress-dependent regulation of 2-Cys Prx provides a means of defense systems in cells to adapt stress conditions by activating intracellular defense signaling pathways. Particularly, 2-Cys Prxs in plants are localized in chloroplasts with a dynamic protein structure. The protein undergoes conformational changes again oxidative stress. Depending on a redox-potential of the chloroplasts, the plant 2-Cys Prx forms super-molecular weight protein structures, which attach to the thylakoid membranes in a reversible manner.

Development and Application of Scientific Inquiry-based STEAM Education Program for Free-Learning Semester in Middle School (중학교 자유학기제에 적합한 과학 탐구 중심의 융합인재교육 프로그램 개발 및 적용)

  • Jeong, Hyeondo;Lee, Hyonyong
    • Journal of Science Education
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    • v.41 no.3
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    • pp.334-350
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    • 2017
  • The purposes of this study are to develop scientific-inquiry based on STEAM education program and to investigate the effects of the program on middle-school students' interests, self-efficacy, and career choice about science, technology/engineering, and mathematics. In order to develop this program, the literature investigation and previous studies were conducted, so that finally the developmental direction was based on scientific inquiry and the developmental theme and model were selected. A total 92 first-graders in G middle-school of Daegu city were participated in this study. A single group pre-post test paired t-test was conducted to figure out changes of students' interest, self-efficacy, and career choices before or after applying this program. In addition, in-depth interviews were conducted with 14 students to find their specific responses. The results of this study were as follows. First, STEAM education program on the theme of 'RC Airplane' was developed on the basis of the 'ADBA' model. Second, the developed STEAM educational program not only results a decisive difference statistically but also has significant effects on middle-school students' interests, self-efficacy, and career choice in science, technology/engineering, and mathematics, who are involved in the free-semester program, across the overall affective domain. In conclusion, the STEAM educational program in this study could affect significant meanings to middle-school students during the free-semester. It could contribute to facilitate middle-school students' education for happiness and to grow the creative STEAM talents.

Optimization of Support Vector Machines for Financial Forecasting (재무예측을 위한 Support Vector Machine의 최적화)

  • Kim, Kyoung-Jae;Ahn, Hyun-Chul
    • Journal of Intelligence and Information Systems
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    • v.17 no.4
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    • pp.241-254
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    • 2011
  • Financial time-series forecasting is one of the most important issues because it is essential for the risk management of financial institutions. Therefore, researchers have tried to forecast financial time-series using various data mining techniques such as regression, artificial neural networks, decision trees, k-nearest neighbor etc. Recently, support vector machines (SVMs) are popularly applied to this research area because they have advantages that they don't require huge training data and have low possibility of overfitting. However, a user must determine several design factors by heuristics in order to use SVM. For example, the selection of appropriate kernel function and its parameters and proper feature subset selection are major design factors of SVM. Other than these factors, the proper selection of instance subset may also improve the forecasting performance of SVM by eliminating irrelevant and distorting training instances. Nonetheless, there have been few studies that have applied instance selection to SVM, especially in the domain of stock market prediction. Instance selection tries to choose proper instance subsets from original training data. It may be considered as a method of knowledge refinement and it maintains the instance-base. This study proposes the novel instance selection algorithm for SVMs. The proposed technique in this study uses genetic algorithm (GA) to optimize instance selection process with parameter optimization simultaneously. We call the model as ISVM (SVM with Instance selection) in this study. Experiments on stock market data are implemented using ISVM. In this study, the GA searches for optimal or near-optimal values of kernel parameters and relevant instances for SVMs. This study needs two sets of parameters in chromosomes in GA setting : The codes for kernel parameters and for instance selection. For the controlling parameters of the GA search, the population size is set at 50 organisms and the value of the crossover rate is set at 0.7 while the mutation rate is 0.1. As the stopping condition, 50 generations are permitted. The application data used in this study consists of technical indicators and the direction of change in the daily Korea stock price index (KOSPI). The total number of samples is 2218 trading days. We separate the whole data into three subsets as training, test, hold-out data set. The number of data in each subset is 1056, 581, 581 respectively. This study compares ISVM to several comparative models including logistic regression (logit), backpropagation neural networks (ANN), nearest neighbor (1-NN), conventional SVM (SVM) and SVM with the optimized parameters (PSVM). In especial, PSVM uses optimized kernel parameters by the genetic algorithm. The experimental results show that ISVM outperforms 1-NN by 15.32%, ANN by 6.89%, Logit and SVM by 5.34%, and PSVM by 4.82% for the holdout data. For ISVM, only 556 data from 1056 original training data are used to produce the result. In addition, the two-sample test for proportions is used to examine whether ISVM significantly outperforms other comparative models. The results indicate that ISVM outperforms ANN and 1-NN at the 1% statistical significance level. In addition, ISVM performs better than Logit, SVM and PSVM at the 5% statistical significance level.

Textural Implications of Fine-Grained Peridotite Xenoliths in Basaltic Rocks from Jeju Island (제주도 현무암에 포획된 세립질 맨틀 페리도타이트 포획암의 조직적 특성)

  • Yang, Kyoung-Hee;Nam, Bok-Hyun;Kim, Jin-Seop;Szabo, Csaba
    • Journal of the Mineralogical Society of Korea
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    • v.22 no.1
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    • pp.1-11
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    • 2009
  • Fine-grained peridotite xenoliths are rarely trapped in the basaltic rocks from the southeastern part of Jeju Island. Based on textural characteristics of the constituent phases showing uniform-sized, fine-grained tabular to mosaic grains with rare porphyroclastic relics, the studied samples can be defined as fine-grained, foliated porphyroclastic peridotites (FPP). Almost no significant difference among the FPPs in textures and major element compositions implies that the FPPs were derived from a structural domain, experiencing similar deformation events and deformation patterns. Moreover, the bimodal distribution with kink-banded porphyroclasts ($2{\sim}3mm$) and stain-free neoblasts ($200{\sim}300{\mu}m$), straight to gently curved grain boundaries with triple junctions, interstitial melt pockets, and microstructures for migrating grain boundary suggest that the studied samples went through dynamic recrystallization (${\pm}$ static recrystallization) in the presence of melt/fluid movement along foliation planes. No notable difference between the FPP and common protogranular xenoliths in major element compositions and geochemical evolution also implies that the FPP and protogranular xenoliths were from a similar horizon. Thus, the textural and geochemical characteristics of the FPPs reflects deformation events occurred at a localized and narrow zone within the lithospheric mantle beneath the Jeju Island. Although further detailed studies are necessary to define deformation events, the most possible process which could trigger deformation in the FPP in the rigid upper mantle was the ascending basaltic magma forming high-stress deformation zones. The suggested high-stress deformation zones in the lithosphere beneath the Jeju Island may be produced by paleo-faulting events related to the ascent of basalt magma before Jeju Island was formed.

Rationalizing Strategies for Children's Activity Spaces and Facilities (어린이 활동공간 및 놀이시설 제도 합리화 방안)

  • Park, Mi-Ok;Koo, Bon-Hak
    • Journal of the Korean Institute of Landscape Architecture
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    • v.40 no.4
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    • pp.36-50
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    • 2012
  • This study was carried out to find contradiction factors on laws for children's activity spaces and facilities and to suggest the rational options to control and manage those spaces and facilities by environmental and landscape planning methods. The results of this study are as follows: 1. The major laws related to the environmental safety for children's activity spaces are "Environmental Health Act (ERA)" for managing the environmental safety of children's activity spaces; "Safety Supervision Law of Children's Play Facilities(SSLCPF)" for the inspection and management for safety of children's play facilities; "Quality Management and Industrial Products Safety Management Law(QMIPSML)" for managing safety certification on children's play equipments. 2. The interior space such as "living room" by the Children's Welfare Law(CWL), "Children Park" by the Act on Urban Parks and Green Spaces(AUPGS), "classroom" on private educational institutes by the Act on Establishment and Operation Private Lesson and Training(AEOPLT) and "nursing room" of child care center smaller than $430m^2$ are needed to be managed as an activity space. 3. In order to reduce industrial burden in the production, establishment, construction, and operation and to minimize unwilling extra burden in the administration effort due to legally double regulate, it is necessary to mitigate the inspections on the equipment certificate from QMIPSML and overlapped or different factors and standards must be unified. With this study, the landscape domain could he enlarged from producing, import of play equipment and establishment, construction and operation of play facilities for a comprehensive range of activity spaces, and the landscape industry such as engineering industry, academic research, management, etc.

Balance of Power and the Relative Military Capacity - Empirical Analysis and Implication to North East Asia - (세력균형(power balance)에서의 군사력 수준과 동북아시아에 주는 함의)

  • Kim, Myung-soo
    • Strategy21
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    • s.38
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    • pp.112-162
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    • 2015
  • This study began to confirm or review the balance of power theory by applying scientific methods through experiential cases. Though there are several kinds of national power, this study supposes military power as a crucial power when it comes to war and peace. This research covered balance and imbalance through comparing relative military power between nations or nations' group. Comparison of relative military power can be achieved by statistically processing the values of which has been converted into the standard variables in same domain, then calculating the values of nation's power which has been synthesized different experiential factors. In addition, the criteria of experiential experiment is highly dedicated to European countries, USA, Japan prior to 1st and 2nd World War, as well as USA, Soviet Union and North East Asia during Cold War era. In addition, the balance of power theory has been redefined to review the action of the state upon the changes of power as mentioned in the theory. To begin with, the redefined theory states that relative level of military power between nations defines the consistency of peace and balance of power. If military power is enough to be on the range of level required to keep the power in equilibrium, peace and balance can be achieved. The opposite would unbalance the military power, causing conflicts. While the relative military level between nations change, nations seek to establish 'nations group' via military cooperation such as alliance, which also shift relative military power between nations group as well. Thus, in order to achieve balance of power, a nation seeks to strengthen its military power(self-help), while pursuing military cooperation(or alliance). This changes relative military power between nations group also. In other words, if there exists balance of power between nations, there is balance of power between nations group as well. In this theory, WWI and II broke out due to the imbalance of military force between nations and nations group, and reviewed that due to the balance of military force during the Cold War, peace was maintained. WWI was resulted from imbalance of military cooperation between two powerful states group and WWII was occurred because of the imbalance among the states. Peace was maintained from cooperation of military power and balance among the states during the Cold War. Imbalance among continental states is more threatening than maritime states and balance of power made by army force and naval force also is feasible. Also the outcomes of two variables are found military power balanced ratio of military power for balance is 67% when variable ratio of balance is 100% and standard value for balance is 0.86. Military power exists in a form of range. The range is what unstabilized the international system causing nations to supplement their military powers. These results made possible the calculation and comparison between state's military power. How balance of power inflicted war and peace has been studied through scientific reviews. Military conflict is highly possible upon already unbalanced military powers of North East Asian countries, if the US draws its power back to America. China and Japan are constantly building up their military force. On the other hand, Korean military force is inferior so in accordance to change of international situation state's survival could be threatened and it is difficult to achieve drastic increase in military force like Germany did. Especially constructing naval force demands lots of time; however but has benefit that naval force can overcome imbalance between continental states and maritime states.

Developing a Project and Program Management Capability Assessment System for the Korean Construction Management Firms (국내 CM 기업의 프로젝트 및 프로그램 관리역량 평가를 위한 자가 역량 평가 시스템 개발)

  • Choi, Jaehyun;Son, Jaeho;Kim, Jihye
    • Korean Journal of Construction Engineering and Management
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    • v.16 no.1
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    • pp.3-14
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    • 2015
  • Since the global financial crisis, the Korean domestic construction market has continuously experienced downturns, and the Korean domain construction firms'profitability has been persistently deteriorated. Domestic construction firms have rapidly advanced to overseas markets exclusively for the construction contract packages. However, the profitability for the construction contracts has been lower compared to engineering or project management contracts. One of the critical issues the Korean firms have faced was project management capability across all phases in project execution. Even though several project management capability assessment tools were introduced, most tools were applicable to a wide variety of industry sectors rather than construction industry. Project management capability assessment tool specifically applicable to domestic CM firms was developed through this research, in order to assess project and program management capabilities and improve the competitiveness in overseas market Also, the correlation between project, programs, and the CM infrastructure were identified. The CM firms were divided into two groups according to the size of the business, and both were evaluated at the project and the program level based for the 9 different criteria. The project management capability assessment tool developed for the CM firms can be used for self-assessment to distinguish the strengths and weaknesses of each company at the project and program level. In addition, the current status of each group can be identified by spotting improvement areas for the management capabilities.

A case of Hyper-IgE syndrome with a mutation of the STAT3 gene (STAT3유전자 돌연변이 검사로 확진된 고면역글로불린E 증후군 1례)

  • Kang, Ji-Man;Suh, Jung-Min;Kim, Ji-Hyun;Kim, Hee-Jin;Kim, Yae-Jean;Lee, Hun-Seok;Shin, Young-Kee;Ahn, Kang-Mo;Lee, Sang-Il
    • Clinical and Experimental Pediatrics
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    • v.53 no.4
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    • pp.592-597
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    • 2010
  • Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disease which is characterized by high serum IgE levels, eczema, and recurrent infections. Herein we present the case of a patient with HIES associated with STAT3 gene ($stat3$) mutation. A 16 year-old girl was admitted to our hospital due to hemoptysis caused by pneumonia with bronchiectasis. She had a history of recurrent skin and respiratory tract infections, such as pneumonia caused by MRSA (methicillin-resistant $Staphylococcus$ $aureus$) and $Pseudomonas$ $aeruginosa$. On physical examination, a broad round shaped nose, oral thrush, and chronic eczematous skin rash over her whole body were found. Laboratory data showed an elevated eosinophil count ($750/{\mu}L$) and total IgE level (5,001 U/mL). The patient's National Institutes of Health (NIH) score for HIES was 44. Direct sequencing of the STAT3 gene revealed that the patient was heterozygous for a missense mutation in the DNA binding domain of the STAT3 protein (c.1144C>T, p. Arg382Trp). HIES should be suspected in patients with recurrent infections and can be confirmed by clinical scoring and genetic analysis.

Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionic Gonadotropin Receptor

  • Min, K.S.
    • Korean Journal of Animal Reproduction
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    • v.24 no.4
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    • pp.357-364
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$ -subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$-subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t631 or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632~653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agoinst-occupied receptors ~2- and ~17- fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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