• Title/Summary/Keyword: association role

Search Result 9,268, Processing Time 0.038 seconds

Type and Dependency of R&D Cooperation Partners and Innovation Performance: An Empirical Study with Korean Venture Firms (R&D 협력 파트너 유형 및 의존도와 혁신의 성과: 한국 벤처기업들을 대상으로 한 실증연구)

  • Kim, Nami;Kim, Eonsoo
    • The Journal of Small Business Innovation
    • /
    • v.19 no.4
    • /
    • pp.1-17
    • /
    • 2016
  • The purpose of this study is to suggest an efficient way for ventures to achieve innovation performance through R&D cooperative arrangements. Achieving innovation is one of the critical factors for the survival of ventures. Unlike established firms, ventures often do not have the specialized assets necessary to take technological developments to the product and market stages. Young and resource-constrained firms can achieve innovation by finding and accessing to the complementary resources from R&D cooperation. In the current business environment, many firms are likely to engage in multiple simultaneous R&D cooperations with different partners. Recent research stream addresses the importance of efficient cooperation management from the holistic portfolio perspective. Since maintaining the multiple cooperative relations require substantial amount of time and effort, managing cooperative relationships play a more important role to resource-constrained firms. In order to find an efficient composition of R&D cooperative partners, we mainly focus on the diversity of partner type and dependence level in partnership. We analyze the data on Korean manufacturing ventures collected in the Korean Innovation Survey (KIS) which was conducted by the Science and Technology Policy Institute (STEPI). The KIS questionnaire assesses the existence of cooperative relationships with different types of partners respectively. The types of cooperating partners are affiliated companies, suppliers, clients & customers, competitors or other firms in the same industry, consulting firms, universities, and research institutes. We confirm that ventures obtain relatively higher benefits from R&D cooperation compared with established firms in terms of innovation performance. The results show that a moderate level of diversity in cooperative partner type composition increases innovation. Moreover, diversity of cooperation dependency among the partners enhances innovation performance. Likewise, concentrating on the quality aspects of cooperative composition, such as diversity of partners and degree of dependencies, this study offers some implications for ventures in managing partners from an integrative perspective.

  • PDF

The Behavior Analysis of Exhibition Visitors using Data Mining Technique at the KIDS & EDU EXPO for Children (유아교육 박람회에서 데이터마이닝 기법을 이용한 전시 관람 행동 패턴 분석)

  • Jung, Min-Kyu;Kim, Hyea-Kyeong;Choi, Il-Young;Lee, Kyoung-Jun;Kim, Jae-Kyeong
    • Journal of Intelligence and Information Systems
    • /
    • v.17 no.2
    • /
    • pp.77-96
    • /
    • 2011
  • An exhibition is defined as market events for specific duration to present exhibitors' main products to business or private visitors, and it plays a key role as effective marketing channels. As the importance of exhibition is getting more and more, domestic exhibition industry has achieved such a great quantitative growth. But, In contrast to the quantitative growth of domestic exhibition industry, the qualitative growth of Exhibition has not achieved competent growth. In order to improve the quality of exhibition, we need to understand the preference or behavior characteristics of visitors and to increase the level of visitors' attention and satisfaction through the understanding of visitors. So, in this paper, we used the observation survey method which is a kind of field research to understand visitors and collect the real data for the analysis of behavior pattern. And this research proposed the following methodology framework consisting of three steps. First step is to select a suitable exhibition to apply for our method. Second step is to implement the observation survey method. And we collect the real data for further analysis. In this paper, we conducted the observation survey method to obtain the real data of the KIDS & EDU EXPO for Children in SETEC. Our methodology was conducted on 160 visitors and 78 booths from November 4th to 6th in 2010. And, the last step is to analyze the record data through observation. In this step, we analyze the feature of exhibition using Demographic Characteristics collected by observation survey method at first. And then we analyze the individual booth features by the records of visited booth. Through the analysis of individual booth features, we can figure out what kind of events attract the attention of visitors and what kind of marketing activities affect the behavior pattern of visitors. But, since previous research considered only individual features influenced by exhibition, the research about the correlation among features is not performed much. So, in this research, additional analysis is carried out to supplement the existing research with data mining techniques. And we analyze the relation among booths using data mining techniques to know behavior patterns of visitors. Among data mining techniques, we make use of two data mining techniques, such as clustering analysis and ARM(Association Rule Mining) analysis. In clustering analysis, we use K-means algorithm to figure out the correlation among booths. Through data mining techniques, we figure out that there are two important features to affect visitors' behavior patterns in exhibition. One is the geographical features of booths. The other is the exhibit contents of booths. Those features are considered when the organizer of exhibition plans next exhibition. Therefore, the results of our analysis are expected to provide guideline to understanding visitors and some valuable insights for the exhibition from the earlier phases of exhibition planning. Also, this research would be a good way to increase the quality of visitor satisfaction. Visitors' movement paths, booth location, and distances between each booth are considered to plan next exhibition in advance. This research was conducted at the KIDS & EDU EXPO for Children in SETEC(Seoul Trade Exhibition & Convention), but it has some constraints to be applied directly to other exhibitions. Also, the results were derived from a limited number of data samples. In order to obtain more accurate and reliable results, it is necessary to conduct more experiments based on larger data samples and exhibitions on a variety of genres.

Nutritional and Tissue Specificity of IGF-I and IGFBP-2 Gene Expression in Growing Chickens - A Review -

  • Kita, K.;Nagao, K.;Okumura, J.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.18 no.5
    • /
    • pp.747-754
    • /
    • 2005
  • Nutritional regulation of gene expression associated with growth and feeding behavior in avian species can become an important technique to improve poultry production according to the supply of nutrients in the diet. Insulin-like growth factor-I (IGF-I) found in chickens has been characterized to be a 70 amino acid polypeptide and plays an important role in growth and metabolism. Although it is been well known that IGF-I is highly associated with embryonic development and post-hatching growth, changes in the distribution of IGF-I gene expression throughout early- to late-embryogenesis have not been studied so far. We revealed that the developmental pattern of IGF-I gene expression during embryogenesis differed among various tissues. No bands of IGF-I mRNA were detected in embryonic liver at 7 days of incubation, and thereafter the amount of hepatic IGF-I mRNA was increased from 14 to 20 days of incubation. In eyes, a peak in IGF-I mRNA levels occurred at mid-embryogenesis, but by contrast, IGF-I mRNA was barely detectable in the heart throughout all incubation periods. In the muscle, no significant difference in IGF-I gene expression was observed during different stages of embryogenesis. After hatching, hepatic IGF-I gene expression as well as plasma IGF-I concentration increases rapidly with age, reaches a peak before sexual maturity, and then declines. The IGF-I gene expression is very sensitive to changes in nutritional conditions. Food-restriction and fasting decreased hepatic IGF-I gene expression and refeeding restored IGF-I gene expression to the level of fed chickens. Dietary protein is also a very strong factor in changing hepatic IGF-I gene expression. Refeeding with dietary protein alone successfully restored hepatic IGF-I gene expression of fasted chickens to the level of fed controls. In most circumstances, IGF-I makes a complex with specific high-affinity IGF-binding proteins (IGFBPs). So far, four different IGFBPs have been identified in avian species and the major IGFBP in chicken plasma has been reported to be IGFBP-2. We studied the relationship between nutritional status and IGFBP-2 gene expression in various tissues of young chickens. In the liver of fed chickens, almost no IGFBP-2 mRNA was detected. However, fasting markedly increased hepatic IGFBP-2 gene expression, and the level was reduced after refeeding. In the gizzard of well-fed young chickens, IGFBP-2 gene expression was detected and fasting significantly elevated gizzard IGFBP-2 mRNA levels to about double that of fed controls. After refeeding, gizzard IGFBP-2 gene expression decreased similar to hepatic IGFBP-2 gene expression. In the brain, IGFBP-2 mRNA was observed in fed chickens and had significantly decreased by fasting. In the kidney, IGFBP-2 gene expression was observed but not influenced by fasting and refeeding. Recently, we have demonstrated in vivo that gizzard and hepatic IGFBP-2 gene expression in fasted chickens was rapidly reduced by intravenous administration of insulin, as indicated that in young chickens the reduction in gizzard and hepatic IGFBP-2 gene expression in vivo stimulated by malnutrition may be, in part, regulated by means of the increase in plasma insulin concentration via an insulin-response element. The influence of dietary protein source (isolated soybean protein vs. casein) and the supplementation of essential amino acids on gizzard IGFBP-2 gene expression was examined. In both soybean protein and casein diet groups, the deficiency of essential amino acids stimulated chickens to increase gizzard IGFBP-2 gene expression. Although amino acid supplementation of a soybean protein diet significantly decreased gizzard IGFBP-2 mRNA levels, a similar reduction was not observed in chickens fed a casein diet supplemented with amino acids. This overview of nutritional regulation of IGF-I and IGFBP-2 gene expression in young chickens would serve for the establishment of the supply of nutrients to diets to improve poultry production.

Proteomic Assessment of the Relevant Factors Affecting Pork Meat Quality Associated with Longissimus dorsi Muscles in Duroc Pigs

  • Cho, Jin Hyoung;Lee, Ra Ham;Jeon, Young-Joo;Park, Seon-Min;Shin, Jae-Cheon;Kim, Seok-Ho;Jeong, Jin Young;Kang, Hyun-sung;Choi, Nag-Jin;Seo, Kang Seok;Cho, Young Sik;Kim, MinSeok S.;Ko, Sungho;Seo, Jae-Min;Lee, Seung-Youp;Shim, Jung-Hyun;Chae, Jung-Il
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.29 no.11
    • /
    • pp.1653-1663
    • /
    • 2016
  • Meat quality is a complex trait influenced by many factors, including genetics, nutrition, feeding environment, animal handling, and their interactions. To elucidate relevant factors affecting pork quality associated with oxidative stress and muscle development, we analyzed protein expression in high quality longissimus dorsi muscles (HQLD) and low quality longissimus dorsi muscles (LQLD) from Duroc pigs by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis. Between HQLD (n = 20) and LQLD (n = 20) Duroc pigs, 24 differentially expressed proteins were identified by LC-MS/MS. A total of 10 and 14 proteins were highly expressed in HQLD and LQLD, respectively. The 24 proteins have putative functions in the following seven categories: catalytic activity (31%), ATPase activity (19%), oxidoreductase activity (13%), cytoskeletal protein binding (13%), actin binding (12%), calcium ion binding (6%), and structural constituent of muscle (6%). Silver-stained image analysis revealed significant differential expression of lactate dehydrogenase A (LDHA) between HQLD and LQLD Duroc pigs. LDHA was subjected to in vitro study of myogenesis under oxidative stress conditions and LDH activity assay to verification its role in oxidative stress. No significant difference of mRNA expression level of LDHA was found between normal and oxidative stress condition. However, LDH activity was significantly higher under oxidative stress condition than at normal condition using in vitro model of myogenesis. The highly expressed LDHA was positively correlated with LQLD. Moreover, LDHA activity increased by oxidative stress was reduced by antioxidant resveratrol. This paper emphasizes the importance of differential expression patterns of proteins and their interaction for the development of meat quality traits. Our proteome data provides valuable information on important factors which might aid in the regulation of muscle development and the improvement of meat quality in longissimus dorsi muscles of Duroc pigs under oxidative stress conditions.

Role of p-38 MAP Kinase in apoptosis of hypoxia-induced osteoblasts (저산소 상태로 인한 조골세포 고사사기전에서 p-38 MAP kinase의 역할에 관한 연구)

  • Yoon, Jeong-Hyeon;Jeong, Ae-Jin;Kang, Kyung-Hwa;Kim, Sang-Cheol
    • The korean journal of orthodontics
    • /
    • v.33 no.3 s.98
    • /
    • pp.169-183
    • /
    • 2003
  • Tooth movement by orthodontic force effects great tissue changes within the periodontium, especially by shifting the blood flow in the pressure side and resulting in a hypoxic state of low oxygen tension. The aim of this study is to elucidate the possible mechanism of apoptosis in response to hypoxia in MC3T3El osteoblasts, the main cells in bone remodeling during orthodontic tooth movement. MC3T3El osteoblasts under hypoxic conditions ($2\%$ orygen) resulted in apoptosis in a time-dependent manner as estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent dye, Hoechst 33258. Pretreatment with Z-VAD-FMK, a pancaspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to hypoxia. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm what caspases are involved in apoptosis, Western blot analysis was performed using anti-caspase-3 or -6 antibodies. The 10-kDa protein, corresponding to the active products of caspase-3, and the 10-kDa protein of the active protein of caspase-6 were generated in hypoxia-challenged cells in which the processing of the full length form of caspase-3 and -6 was evident. While a time course similar to this caspase-3 and -6 activation was evident, hypoxic stress caused the cleavage of lamin A, which was typical of caspase-6 activity. In addition, the stress elicited the release of cytochrome c into the cytosol during apoptosis. Furthermore, we observed that pre-treatment with SB203580, a selective p38 mitogen activated protein kinase inhibitor, attenuated the hypoxia-induced apoptosis. The addition of SB203S80 suppressed caspase-3 and -6-like protease activity by hypoxia up to $50\%$. In contrast, PD98059 had no effect on the hypoxia-induced apoptosis. To confirm the involvement of MAP kinase, JNK/SAPK, ERK, or p38 kinase assay was performed. Although p38 MAPK was activated in response to hypoxic treatment, the other MAPK -JNK/SAPK or ERK- was either only modestly activated or not at all. These results suggest that p38 MAPK is involved in hypoxia-induced apoptosis in MC3T3El osteoblasts.

Psychosocial Characteristics and Factors Associated with Referral to Psychiatric Care in the Suicide Attempters Visiting Emergency Center (응급실에 내원한 자살 시도자들의 정신사회학적 특성과 정신건강의학과 진료 의뢰 관련 요인)

  • Kwon, Jung-Woo;Ko, Young-Hoon;Han, Chang-Su;Lee, Moon-Soo;Yoon, Ho-Kyung;Lee, Hongjae
    • Korean Journal of Psychosomatic Medicine
    • /
    • v.21 no.2
    • /
    • pp.106-113
    • /
    • 2013
  • Objectives: The purpose of this study was to examine the characteristics and the psychosocial factors associated to the referral to psychiatric care in the suicide attempters visiting emergency center. Methods: We conducted a systematic chart review of 377 suicidal attempters visiting emergency center of the Korea University Ansan Hospital between January 2008 and December 2011. We gathered a data contain 20 items including psychosocial characteristics and factors related to suicide and factors related to psychiatric treatment. Multivariate logistic regression models were fitted to data to estimate the unique effects of sex, drunken status, companion, suicidal methods, place of suicide and current use of psychiatric medication on the referral to psychiatric care. Results: The female gender(OR=1.63, 95% CI=0.99-2.69), suicidal attempts at home(OR=3.40, 95% I= 1.21-9.56) and drunken state at visit(OR=2.34, 95% CI=1.10-5.01) are the factors that predict the risk of the non-referral of the patients to psychiatric intervention. Place of suicidal attempt was the most important factor do play a role in determining whether referral to psychiatric care will take place or not. Current use of psychiatric medication showed a trend toward significance(p=0.08, OR=1.67, 95% CI=0.95-2.95). Conclusions: These results suggest that when deciding whether to adapt or to refuse the referral to psychiatric care, the factors such as suicidal intent, lethality of suicide methods, familiar factors and alcohol may contribute onto the referral to psychiatric care. Additional research is required to investigate an association of these factors with referral to psychiatric care.

  • PDF

The Effects of Depression on the Survival of Terminal Cancer Patients in a Palliative Care Unit (완화병동에 입원한 말기 암 환자에서 우울증이 생존기간에 미치는 영향)

  • Son, Ji-Sung;Kim, Won-Hyoung;Lee, Jeong-Seop;Kim, Hye-Young;Kang, Sang-Gu;Choi, Seo-Hyeon;Bae, Jae-Nam
    • Korean Journal of Psychosomatic Medicine
    • /
    • v.27 no.2
    • /
    • pp.138-146
    • /
    • 2019
  • Objectives : This study examined the association between depression and survival time in terminal cancer patients admitted to the palliative care unit. Emotional problems are important for terminal cancer patients in the palliative care unit, and evaluation of patients' depression plays an important role in treatment planning. Methods : From October 2015 to August 2018, we conducted a retrospective study of 291 terminal cancer patients admitted to a palliative care unit at a university hospital and evaluated depression with PHQ-9 at admission. Of the 291 patients, 146 (50.2%) completed PHQ-9 but 145 (49.8%) were not evaluated due to loss of consciousness or rejection. Results : 4-week survival rate in the Kaplan-Meier survival analysis were 45.4% in the non-depressed group (PHQ-9<10) and 18.7% in the depressed group (PHQ-9≥10). According to the severity of depression, in the Cox proportional hazard model, the risk of mortality in moderate, moderately sever and severe group was 2.778, 1.882 and 3.423 times higher than minimal group, respectively. Conclusions : Of the patients with terminal cancer who were admitted to the palliative care unit, the survival time was shorter in the depressed group than in the non-depressed group. Further research is needed to determine if treatment of depression increase the survival in terminal cancer patients.

The Effects of Organization Characteristics and Relationship Characteristics on Relational Performance: Focused on Mediating Effects of the Dimensions of Trust and Commitment (조직특성과 관계특성이 관계성과에 미치는 영향: 신뢰 차원과 결속 차원의 매개효과를 중심으로)

  • Sung, Min;Oh, Se-Jo
    • Journal of Distribution Research
    • /
    • v.12 no.1
    • /
    • pp.1-31
    • /
    • 2007
  • While trust and commitment are core mediating variables for the purpose of maintaining the long-term relationship, in the context of the characteristics of company and the relationship performance of its members, there have been limited studies which explore as to how each of the dimensions has affects differently. The basic purpose of this study is to examine the relationship between an automobile manufacturer and its agencies. The main purpose of this study is to examine how each different dimension of trust and commitment on the automobile manufacturer has different mediating effects between the characteristics of company(organization characteristics, relationship characteristics) and relationship performance perceived by its agents. Another purpose is to investigate the mechanism by which the relationship performance of the agencies is improved. An empirical study surveying 115 sales office managers at a leading automobile manufacturer in Korea was conducted. An analysis of the collected data indicates that while the characteristics of company have a positive influence on the agencies' relational performance through the mediating role of both trust of benevolence and commitment, agencies' trust of their headquarter's benevolence has a different influence on the dimensions of commitment. Finally, the authors discussed some theoretical contributions and managerial implications. And then, they presented limitations of this study and the future research directions.

  • PDF

The Contribution of Innovation Activity to the Output Growth of Emerging Economies: The Case of Kazakhstan

  • Smagulova, Sholpan;Mukasheva, Saltanat
    • Journal of Distribution Science
    • /
    • v.10 no.7
    • /
    • pp.33-41
    • /
    • 2012
  • The purpose of this study is to analyse the state of the energy industry and to determine the efficiency of its functioning on the basis of energy conservation principle and application of innovative technologies aimed at improving the ecological modernisation of agricultural sectors of Kazakhstan. The research methodology is based on an integrated approach of financial and economic evaluation of the effectiveness of the investment project, based on calculation of elasticity, total costs and profitability, as well as on comparative, graphical and system analysis. The current stage is characterised by widely spread restructuring processes of electric power industry in many countries through introduction of new technical installations of energy facilities and increased government regulation in order to enhance the competitive advantage of electricity market. Electric power industry features a considerable value of creating areas. For example, by providing scientific and technical progress, it crucially affects not only the development but also the territorial organisation of productive forces, first of all the industry. In modern life, more than 90% of electricity and heat is obtained by Kazakhstan's economy by consuming non-renewable energy resources: different types of coal, oil shale, oil, natural gas and peat. Therefore, it is significant to ensure energy security, as the country faces a rapid fall back to mono-gas structure of fuel and energy balance. However, energy resources in Kazakhstan are spread very unevenly. Its main supplies are concentrated in northern and central parts of the republic, and the majority of consumers of electrical power live in the southern and western areas of the country. However, energy plays an important role in the economy of industrial production and to a large extent determines the level of competitive advantage, which is a promising condition for implementation of energy-saving and environmentally friendly technologies. In these circumstances, issues of modernisation and reforms of this sector in Kazakhstan gain more and more importance, which can be seen in the example of economically sustainable solutions of a large local monopoly company, significant savings in capital investment and efficiency of implementation of an investment project. A major disadvantage of development of electricity distribution companies is the prevalence of very high moral and physical amortisation of equipment, reaching almost 70-80%, which significantly increases the operating costs. For example, while an investment of 12 billion tenge was planned in 2009 in this branch, in 2012 it is planned to invest more than 17 billion. Obviously, despite the absolute increase, the rate of investment is still quite low, as the total demand in this area is at least more than 250 billion tenge. In addition, industrial infrastructure, including the objects of Kazakhstan electric power industry, have a tangible adverse impact on the environment. Thus, since there is a large number of various power projects that are sources of electromagnetic radiation, the environment is deteriorated. Hence, there is a need to optimise the efficiency of the organisation and management of production activities of energy companies, to create and implement new technologies, to ensure safe production and provide solutions to various environmental aspects. These are key strategic factors to ensure success of the modern energy sector of Kazakhstan. The contribution of authors in developing the scope of this subject is explained by the fact that there was not enough research in the energy sector, especially in the view of ecological modernisation. This work differs from similar works in Kazakhstan in the way that the proposed method of investment project calculation takes into account the time factor, which compares the current and future value of profit from the implementation of innovative equipment that helps to bring it to actual practise. The feasibility of writing this article lies in the need of forming a public policy in the industrial sector, including optimising the structure of energy disbursing rate, which complies with the terms of future modernised development of the domestic energy sector.

  • PDF

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
    • /
    • v.24 no.4
    • /
    • pp.357-364
    • /
    • 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.

  • PDF