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1.
Clin Radiol ; 79(1): e73-e79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37914602

RESUMO

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigação sanguínea , Estudos Prospectivos , Meios de Contraste , Ultrassonografia/métodos , Imageamento por Ressonância Magnética
2.
Am J Transplant ; 16(1): 44-57, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26430779

RESUMO

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Heme Oxigenase-1/genética , Imunoglobulina G/genética , Transplante das Ilhotas Pancreáticas , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Animais , Apoptose , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/cirurgia , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Ilhotas Pancreáticas/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Transplante Heterólogo
4.
Int Nurs Rev ; 58(2): 263-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21554302

RESUMO

BACKGROUND: Numerous studies on HNC services have been carried out by signifying their needs, efficiency and effectiveness. However, no study has ever been performed to determine the critical factors associated with HNC's positive results despite the deluge of positive studies on the service. METHODS: This study included all of the 89 training hospitals that were practising HNC service in Korea as of November 2006. The input factors affecting the performance were classified as either internal or external environmental factors. This analysis was conducted to understand the impact that the corresponding factors had on performance. Data were analysed by using multiple linear regressions. RESULTS: The internal and external environment variables affected the performance of HNC based on univariate analysis. The meaningful variables were internal environmental factors. Specifically, managerial resource (the number of operating beds and the outpatient/inpatient ratio) were meaningful when the multiple linear regression analysis was performed. Indeed, the importance of organizational culture (the passion of HNC nurses) was significant. CONCLUSION: This study, considering the limited market size of Korea, illustrates that the critical factor for the development of hospital-led HNC lies with internal environmental factors rather than external ones. Among the internal environmental factors, the hospitals' managerial resource-related factors (specifically, the passion of nurses) were the most important contributing element.


Assuntos
Serviços Hospitalares de Assistência Domiciliar , Administração Hospitalar , Hospitais de Ensino , Qualidade da Assistência à Saúde , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Serviços Hospitalares de Assistência Domiciliar/normas , Humanos , Cultura Organizacional , República da Coreia , Carga de Trabalho
5.
Int Nurs Rev ; 58(1): 89-95, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21281299

RESUMO

AIM: The study aims to investigate characteristics associated with intent to stay among Quality Improvement (QI) nurses in Korean hospitals. BACKGROUND: QI nurses have recently emerged as a new specialty area in the nursing profession in Korea. They have played a major role in coordinating and facilitating hospital-wide QI activities. However, their frequent turnover degrades the continuity of overall QI programmes and incurs additional costs in human resource management. METHODS: A cross-sectional questionnaire survey was administered to 123 QI nurses in 123 general hospitals. The collected data included their hospital and department characteristics, work demand, job satisfaction, organizational commitment and demographics. The response rate was 94.3% (n=116). Multiple logistic regression analysis was performed to determine the factors associated with intent to stay. FINDINGS: Only 32.8% intended to stay in their current job. Significant factors associated with intent to stay were affective commitment and work demands. QI nurses with a higher level of affective commitment were more likely to stay [odds ratios (OR)=2.50], whereas those with higher quantitative work demands in QI education and support were less likely to stay (OR=0.40). CONCLUSION: The findings indicated that intent to stay was closely associated with work environment characteristics. Efforts to enhance their affective commitment and support their workload management are needed to increase the retention of qualified and experienced QI nurses.


Assuntos
Recursos Humanos de Enfermagem Hospitalar/psicologia , Reorganização de Recursos Humanos , Melhoria de Qualidade , Especialidades de Enfermagem , Estudos Transversais , Humanos , Intenção , Satisfação no Emprego , Modelos Logísticos , República da Coreia , Inquéritos e Questionários , Recursos Humanos
6.
Phys Rev Lett ; 103(18): 182502, 2009 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-19905801

RESUMO

We have measured the branching ratio of the three-body process in the nonmesonic weak decay of Lambda12C to be 0.29+/-0.13. This result was obtained by reproducing the nucleon and the nucleon pair yields introducing a measured final state interaction. At the same time, we have determined the absolute decay widths, Gamma(n) and Gamma(p), along with Gamma2N, whose relative ratio has been a long-standing puzzle. Including the three-body process, we have successfully reproduced the nucleon energy distribution, the coincidence two-nucleon angular correlation, and the momentum sum distribution simultaneously.

7.
Int Nurs Rev ; 56(3): 313-8, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19702804

RESUMO

BACKGROUND: The nursing shortage has become an internationally important issue. Nurses' professionalism and job satisfaction have been recognized as strong factors influencing their turnover. As international interchanges in nursing education are growing between Korea and China, understanding the commonalities and differences in factors associated with job satisfaction is critical to improving nurses' job retention. AIM: To compare the factors influencing job satisfaction among Korean and Chinese nurses. METHOD: A cross-sectional survey was conducted. The participants were comprised of 693 nurses at three general hospitals in Jinan, People's Republic of China and 593 nurses at two general hospitals in Seoul, Korea. A questionnaire was designed to measure the nurses' professionalism and job satisfaction. Stepwise multiple regression analysis was performed to identify factors related to job satisfaction. RESULTS: Professionalism was the common factor influencing job satisfaction in Korean and Chinese nurses. Professionalism was positively related to job satisfaction in both groups. Additional factors associated with job satisfaction were demographics and job characteristics such as age, job position and department of work, which were significant only in Korean nurses. CONCLUSIONS: Professionalism was the most important factor influencing job satisfaction in both Korean and Chinese nurses. Enhancing nursing professionalism is recommended as a common strategy to improve nurses' job retention across different healthcare systems.


Assuntos
Atitude do Pessoal de Saúde , Satisfação no Emprego , Enfermeiras e Enfermeiros/estatística & dados numéricos , Adulto , Distribuição por Idade , Mobilidade Ocupacional , China , Comparação Transcultural , Estudos Transversais , Escolaridade , Humanos , Estado Civil/estatística & dados numéricos , Pesquisa em Enfermagem , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Análise de Componente Principal , Análise de Regressão , República da Coreia
8.
Int Nurs Rev ; 56(1): 73-80, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19239519

RESUMO

AIM: To examine the impact of work climate perception (WCP) on turnover intention among public hospital personnel in Korea. BACKGROUND: With increased competition and high staff turnover in hospitals, managers focus on human resource management. Positive work climate is considered as a strategy to retain valued staff, but previous studies have shown occupationally different relationships between turnover intention and work environment characteristics as perceived by staff. METHODS: A cross-sectional questionnaire survey was conducted of employees (n = 852) in four public hospitals in Korea to gather information about WCP, intention to leave and demographics. The work climate was measured by 32 items categorized into 13 factors in five dimensions. For each occupation, logistic regression analyses were performed to determine the significant factors of WCP that influenced turnover intention. FINDINGS: Positive WCP inversely influenced turnover intention. For all occupations, the most significant factor was 'workgroup friendliness and warmth' (OR = 0.01-0.21). For the nursing group, an additional significant factor was 'adherence to job standard' (OR = 0.63). In contrast, there were different significant factors for other hospital staff: 'workgroup esprit de corps' (OR = 0.16) and 'role clarity' (OR = 0.19) for physicians, 'adherence to job standard' (OR = 3.08) and 'role adaptation' (OR = 2.23) for paramedicals, and 'flexibility and innovation' (OR = 0.14) and 'interdepartmental cooperation' (OR = 0.19) for administrators. CONCLUSIONS: Nurses with perceptions of work climate emphasizing 'workgroup friendliness and warmth' and 'adherence to job standard' had lower turnover intention. Physicians, paramedicals and administrators have different WCPs. To retain qualified personnel, hospitals should focus on human relations, maintaining a consideration for occupation-specific characteristics.


Assuntos
Atitude do Pessoal de Saúde , Ambiente de Instituições de Saúde/organização & administração , Intenção , Recursos Humanos de Enfermagem Hospitalar/psicologia , Local de Trabalho/psicologia , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Hospitais Públicos , Humanos , Relações Interprofissionais , Coreia (Geográfico) , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem/psicologia , Pesquisa Metodológica em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Cultura Organizacional , Reorganização de Recursos Humanos/estatística & dados numéricos , Análise de Componente Principal , Inquéritos e Questionários , Local de Trabalho/organização & administração , Adulto Jovem
10.
Phys Rev Lett ; 96(6): 062301, 2006 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-16605985

RESUMO

We performed a coincidence measurement of two nucleons emitted from the nonmesonic weak decay of lambda(5)He formed via the 6Li(pi+, K+) reaction. The energies of the two nucleons and the pair number distributions in the opening angle between them were measured. In both np and nn pairs, we observed a clean back-to-back correlation coming from the two-body weak reactions of lambda p --> np and lambda n --> nn, respectively. The ratio of the nucleon pair numbers was N(nn)/N(np) = 0.45 +/- 0.11(stat) +/- 0.03(syst) in the kinematic region of cos theta(NN) < -0.8. Since each decay mode was exclusively detected, the measured ratio should be close to the ratio of gamma(lambda p --> np)/gamma(lambda n --> nn). The ratio is consistent with recent theoretical calculations based on the heavy meson and/or direct-quark exchange picture.

11.
Phys Rev Lett ; 94(5): 052502, 2005 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-15783631

RESUMO

In order to produce a neutron-rich Lambda hypernucleus for the first time, we carried out an experiment by utilizing the (pi-,K+) double charge-exchange reaction on a 10B target. We observed the production of a 10LambdaLi hypernucleus. The cross section for the Lambda bound region was found to be 11.3+/-1.9 nb/sr with the 1.2 GeV/c incident momentum, which is compared with the 10LambdaB hypernucleus production cross section, 7.8+/-0.3 microb/sr, in the (pi+,K+) reaction with a 1.05 GeV/c incident momentum beam.

12.
Phys Rev Lett ; 91(10): 107202, 2003 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-14525501

RESUMO

The chemical states of the ZnGeP(2):Mn interface which shows ferromagnetism above room temperature have been studied by photoemission spectroscopy. Mn deposition on the ZnGeP2 substrate heated to 400 degrees C induced Mn substitution for Zn and then the formation of metallic Mn-Ge-P compounds. Depth profile studies have shown that Mn 3d electrons changed their character from itinerant to localized along the depth, and in the deep region, dilute divalent Mn species (<5% Mn) was observed with a coexisting metallic Fermi edge of non-Mn 3d character. The possibility of hole doping through Mn substitution for Ge and/or Zn vacancy is discussed.

13.
Int Nurs Rev ; 50(1): 44-54, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12581126

RESUMO

This study was conducted to explore the self-rated performance level of quality specialists in Korea in order to provide information to direct the future needs for education and role orientation. The formal identification and appointment of quality specialists in health-care organizations in Korea began in the mid-1990s. The majority of quality specialists, appointed by their hospital, assumed positions without undergoing the prerequisite training or education. Extensive variation in performance has been recognized. The sample (n = 29) in this study included all quality specialists at hospitals in Seoul and Kyung-Gi province. Their performance was rated using a postal questionnaire consisting of a set of activities in five domains (policy development, data collection and analysis, communication and report, education and support, and administration). The response rate was 100%. The respondents had an average of 25.5 months of experience as quality specialists. Self-rated performance of quality-related activities demonstrated wide variation, independent of personal, departmental, or hospital-specific characteristics. The respondents rated their performance highly in the area of communication and reporting. The performance of administrative activities was rated lowest. Perceived differences between desired and actual performance were statistically significant in all activities of each domain, and were largest in policy development, and next in education and support. Self-rated performance among the five domains demonstrated positive, significant correlations. Hence, the findings imply the necessity of a formal education for quality specialists to accelerate balanced growth in all domains of quality activities.


Assuntos
Avaliação de Desempenho Profissional/métodos , Recursos Humanos de Enfermagem Hospitalar , Garantia da Qualidade dos Cuidados de Saúde/métodos , Coleta de Dados , Coreia (Geográfico)
14.
Am J Obstet Gynecol ; 185(5): 1257-60, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11717667

RESUMO

A case of placenta previa increta/percreta was diagnosed at 18 weeks' gestation with the 3-dimensional color power Doppler imaging technique. Unusually extensive uteroplacental vascular network architecture was seen on the 3-dimensional angiohistogram. After appropriate counseling, the patient chose to terminate the pregnancy. A hysterectomy was performed with prophylactic preoperative embolization of internal iliac arteries at 21 weeks' gestation, and histopathologic examination revealed placenta previa increta/percreta. This new 3-dimensional angiohistogram technique allowed us to visualize all 3 orthogonal planes of the angioarchitectural information. It appears to be a useful complementary tool and is likely to play a more defining and clarifying role in assessing the quantification of abnormal uteroplacental neovascularization for patients with placenta previa increta/percreta.


Assuntos
Imageamento Tridimensional , Neovascularização Patológica/diagnóstico por imagem , Placenta Prévia/diagnóstico por imagem , Placenta Prévia/fisiopatologia , Placenta/irrigação sanguínea , Ultrassonografia Doppler em Cores , Útero/irrigação sanguínea , Adulto , Angiografia Digital , Feminino , Humanos , Placenta/diagnóstico por imagem , Gravidez , Útero/diagnóstico por imagem
15.
Biochem Biophys Res Commun ; 288(1): 1-7, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11594744

RESUMO

Mammalian phospholipase C-beta isozymes are activated by a heterotrimeric GTP-binding protein linked to various cell surface receptors. Recent reports suggest that PDZ domain proteins play a significant role of PDZ-containing proteins in the regulation of mammalian PLC-beta isozymes. PDZ-containing proteins mediate the clustering of receptors and signaling molecules and thereby regulate agonist-induced signal transduction in polarized cells such as neuronal and epithelial cells. NORPA, a Drosophila PLC-beta, is known to be a component of a signaling complex that includes TRP and rhodopsin through interaction with INAD, a PDZ-containing protein. Mammalian PLC-beta1 and -beta2 isoforms interact with a PDZ-containing protein NHERF which is coupled to Trp4, a Ca(2+) channel. In addition, PLC-beta3 specifically interacts with E3KARP, another protein closely related to NHERF, through its C-terminal PDZ-binding motif. E3KARP up-regulates the PLC-beta3 activation coupled to muscarinic receptor. In this review, the role of signaling complexes mediated by PDZ-containing proteins in the regulation of PLC-beta isoforms will be discussed.


Assuntos
Proteínas de Drosophila , Isoenzimas/fisiologia , Transdução de Sinais , Fosfolipases Tipo C/fisiologia , Animais , Canais de Cálcio/metabolismo , Proteínas do Citoesqueleto/fisiologia , Drosophila/fisiologia , Proteínas do Olho/metabolismo , Isoenzimas/química , Modelos Biológicos , Fosfolipase C beta , Fosfoproteínas/fisiologia , Estrutura Terciária de Proteína , Trocadores de Sódio-Hidrogênio , Canais de Cátion TRPC , Fosfolipases Tipo C/química , Visão Ocular
16.
FEBS Lett ; 506(3): 239-42, 2001 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-11602253

RESUMO

The molecular interactions of poly(ADP-ribose) polymerase I (PARP I) and topoisomerase I (Topo I) have been determined by the analysis of physical binding of the two proteins and some of their polypeptide components and by the effect of PARP I on the enzymatic catalysis of Topo I. Direct association of Topo I and PARP I as well as the binding of two Topo I polypeptides to PARP I are demonstrated. The effect of PARP I on the 'global' Topo I reaction (scission and religation), and the activation of Topo I by the 36 kDa polypeptide of PARP I and catalytic modifications by poly(ADP-ribosyl)ation are also shown. The covalent binding of Topo I to circular DNA is activated by PARP I similar to the degree of activation of the 'global' Topo I reaction, whereas the religation of DNA is unaffected by PARP I. The geometry of PARP I-Topo I interaction compared to automodified PARP I was reconstructed from direct binding assays between glutathione S-transferase fusion polypeptides of Topo I and PARP I demonstrating highly selective binding, which was correlated with amino acid sequences and with the 'C clamp' model derived from X-ray crystallography.


Assuntos
DNA Topoisomerases Tipo I/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Sítios de Ligação , DNA Circular/metabolismo , Glutationa Transferase/metabolismo , Ligação Proteica
18.
Biochemistry ; 40(4): 1117-23, 2001 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-11170436

RESUMO

Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle. It is highly expressed in a cell cycle-regulated manner and localizes together with caspase-3 on microtubules within centrosomes. Whether survivin is a physiologically relevant caspase inhibitor has been unclear due to the difficulties with obtaining correctly folded survivin and finding the right conditions for inhibition assay. In this study, recombinant, active human survivin was expressed in Escherichia coli and purified to homogeneity. The protein, existing as a homodimer in solution, binds caspase-3 and -7 tightly with dissociation constants of 20.9 and 11.5 nM, respectively, when evaluated by surface plasmon resonance spectroscopy. Consistently, survivin potently inhibits the cleavage of a physiological substrate poly(ADP-ribose) polymerase and an artificial tetrapeptide by caspase-3 and -7 in vitro with apparent inhibition constants of 36.0 and 16.5 nM, respectively. The data suggest that sequestering caspase-3 and -7 in inhibited states on microtubules is at least one mechanism of survivin in the suppression of default apoptosis in the G2/M phase. The localization of survivin on microtubules, which is essential for its function, should increase the protective activity at the action site.


Assuntos
Apoptose , Inibidores de Caspase , Inibidores de Cisteína Proteinase/farmacologia , Proteínas Associadas aos Microtúbulos , Proteínas/fisiologia , Apoptose/efeitos dos fármacos , Caspase 3 , Caspase 7 , Caspases/metabolismo , Sistema Livre de Células/enzimologia , Escherichia coli/genética , Vetores Genéticos , Humanos , Proteínas Inibidoras de Apoptose , Proteínas de Neoplasias , Ligação Proteica , Biossíntese de Proteínas , Dobramento de Proteína , Proteínas/genética , Proteínas/metabolismo , Reticulócitos , Ressonância de Plasmônio de Superfície , Survivina , Temperatura
19.
Biochemistry ; 39(29): 8674-82, 2000 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-10913276

RESUMO

A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras-specific guanine nucleotide exchange factor, directly binds to the SH3 domain of PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC-gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is mediated by direct physical interaction. The carboxyl-terminal proline-rich domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain. Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell lysates. From transient expression studies, we could demonstrate that the SH3 domain of PLC-gamma1 is necessary for the association with SOS1 in vivo. Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC-gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3 domain could not activate p21Ras. p21Ras activities in cell lines overexpressing either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2-fold compared to vector transfected cells. This study is the first to demonstrate that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway.


Assuntos
Isoenzimas/química , Isoenzimas/metabolismo , Proteína SOS1/química , Proteína SOS1/metabolismo , Fosfolipases Tipo C/química , Fosfolipases Tipo C/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Células COS , Linhagem Celular , Primers do DNA/genética , Isoenzimas/genética , Fosfolipase C gama , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteína SOS1/genética , Transfecção , Fosfolipases Tipo C/genética , Domínios de Homologia de src/genética
20.
J Biol Chem ; 275(22): 16632-7, 2000 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-10748023

RESUMO

Among the phospholipase C that catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate, four mammalian phospholipase C-beta (PLC-beta) isotypes (isotypes 1-4) are activated through G protein-coupled receptors (GPCRs). Although the regulation of the PLC-betas by GPCRs and heterotrimeric G proteins has been extensively studied, little is known about the molecular determinants that regulate their activity. The PLC-beta isozymes carry a putative PSD-95/Dlg/ZO-1 (PDZ) binding motif (X(S/T)X(V/L)COOH) at their carboxyl terminus, which is implicated in specific interactions with anchor proteins. Using the yeast two-hybrid system, we identified Na(+)/H(+) exchanger regulatory factor 2 (NHERF2) as a protein that interacted with a C-terminal heptapeptide of PLC-beta3. Immunoprecipitation studies revealed that NHERF2 interacts specifically with PLC-beta3, but not with other PLC-beta isotypes. Furthermore, PLC-beta3 interacted with NHERF2 rather than with other PDZ-containing proteins. This interaction required the COOH-terminal NTQL sequence of PLC-beta3 and the second PDZ domain of NHERF2. Interestingly, NHERF2 potentiated the PLC-beta activation by carbachol in COS7 and HeLa cells, while mutant NHERF2, lacking the second PDZ domain, had no such effect. Taken together, the data suggest that NHERF2 may act as a modulator underlying the process of PLC-beta3-mediated signaling.


Assuntos
Isoenzimas/metabolismo , Fosfoproteínas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Fosfolipases Tipo C/metabolismo , Animais , Sequência de Bases , Células COS , Primers do DNA , Células HeLa , Humanos , Hidrólise , Isoenzimas/química , Leucina/metabolismo , Fosfatidilinositóis/metabolismo , Fosfolipase C beta , Saccharomyces cerevisiae/genética , Transdução de Sinais , Especificidade por Substrato , Treonina/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Fosfolipases Tipo C/química
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