• Title/Summary/Keyword: Src

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Roles of Steroid Receptor Coactivator-3 and TTF-1 in Lung Development and Lung Cancer (폐의 분화와 폐암에서 SRC-3와 TTF-I의 역할)

  • Kwak, Inseok
    • Journal of Life Science
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    • v.25 no.12
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    • pp.1439-1444
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    • 2015
  • Steroid receptor coactivators (SRC) are transcriptional coactivators. Among SRCs, SRC-3 is the most studied in relation to different types of tumors. However, the role of SRC-3 in early lung development and lung cancer has not been well studied. The expression profiles of SRC-3 showed that SRC-3 contributed to bronchial and alveolar development in embryonic lung development. SRC-3 was strongly expressed in Clara cells and type II alveolar cells during fetal lung development (E17.5- E18.5), and SRC-3 was expressed in both cell types in the adult lung. TTF-1 was expressed in the lungs of heterozygote SRC-3 mice and Clara cell-specific-CCSP-TAg tumor mice, along with SRC-3 expression. The expression of TTF-1 was localized at transformed Clara cells and multifocal adenocarcinomas in lung cancer mice. However, SRC-3 was not expressed in the multifocal adenocarcinomas, suggesting that SRC-3 might not be involved in the invasiveness of lung cancer. Cotransfection of TTF-1 in Clara cell-specific mtCC cell lines resulted in significant activation of CCSP expression. However, cotransfection of SRC-3 had no significant effects on transient transfection. These in vivo and in vitro results suggest that SRC-3 does not play a significant role in lung tumor progression. In conclusion, SRC-3 is involved in bronchial and alveolar development in fetal and adult lungs, but it does not play an important role in the progression of Clara cell-derived lung cancer.

Steroid Receptor Coactivator-3 Promotes Bladder Cancer Through Upregulation of CXCR4

  • Zhang, Yu;Wang, Ji-Hong;Liu, Bin;Qu, Ping-Bao
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3847-3850
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    • 2013
  • The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptional co-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have been identified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study, our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdown of SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptional target of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, which may be a target beneficial for its prevention and treatment.

Thermo-Elastic Analysis of the Spatially Reinforced Composite Nozzle (다방향으로 입체 보강된 복합재 노즐의 열탄성해석)

  • 유재석;김광수;이상의;김천곤
    • Proceedings of the Korean Society For Composite Materials Conference
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    • 2002.10a
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    • pp.100-105
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    • 2002
  • This paper predicts the material properties of spatially reinforced composites (SRC) and analyzes the thermo-elastic behavior of a kick motor nozzle manufactured from that material. To find the appropriate SRC structure for the nozzle throat that satisfies given design conditions, the equivalent material properties of the SRC are predicted using the superposition method for those of rod and matrix. Studied are the elastic behavior, temperature distribution, and thermo-elastic behavior of a kick motor nozzle composed of carbon/carbon SRC as a throat part. The elastic deformation of the nozzle composed of 3D carbon/carbon SRC shows asymmetry in a circumferential direction. However, 4D carbon/carbon SRC nozzle shows uniform deformation in the circumferential direction. Stress concentration in connecting parts of the kick motor nozzle is ultimately high due to the high temperature gradient in each connecting part. The thermo-elastic deformations of both the 3D and the 4D SRC nozzles are uniform in the circumferential direction due to the isotropy of CTE of each SRC. The deformation of the 3D SRC nozzle is a slightly smaller than that of the 4D SRC nozzle in the nozzle throat, which is favorably effective on rocket thrust. The circumferential stress is the most critical component of the kick motor nozzle. The 4D SRC nozzle having 1,1,1,1.7 diameters in each direction has the smallest circumferential stress among several SRC nozzles.

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c-Src Antisense Complexed with PAMAM Denderimes Decreases of c-Src Expression and EGFR-Dependent Downstream Genes in the Human HT-29 Colon Cancer Cell Line

  • Nourazarian, Ali Reza;Pashaei-Asl, Roghiyeh;Omidi, Yadollah;Najar, Ahmad Gholamhoseinian
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2235-2240
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    • 2012
  • c-Src is one member of non-receptor tyrosine kinase protein family that has over expression and activation in many human cancer cells. It has been shown that c-Src is implicated in various downstream signaling pathways associated with EGFR-dependent signaling such as MAPK and STAT5 pathways. Transactivation of EGFR by c-Src is more effective than EGFR ligands. To inhibit the c-Src expression, we used c-Src antisense oligonucleotide complexed with PAMAM Denderimes. The effect of c-Src antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay. Then, the expression of c-Src, EGFR and the genes related to EGFR-depended signaling with P53 was applied by real time PCR. We used western blot analysis to elucidate the effect of antisense on the level of c-Src protein expression. The results showed, c-Src antisense complexed with PAMAM denderimers has an effective role in decrease of c-Src expression and EGFR-dependent downstream genes.

생쥐 정소에서 C-terminal Src kinase (Csk) 발현과 Src kinase 활성의 조절

  • 계명찬;최진국;안현수;김영수
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.66-66
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    • 2003
  • Protein tyrosine kinases는 표적단백질의 tyrosine 잔기를 인산화하는 효소로서 다양한 종류의 성장인자, peptide 호르몬, cytokine 수용체 하위의 세포 내 신호전달에 관여한다. Non-receptor tyrosine kinase의 일종인 c-Src는 세포막에서 발생한 ligand-receptor 상호작용 하위의 신호전달에서 중요한 역할을 하며 C-terminal Src kinase (Csk)는 Src kinase의 C-terminal tyrosine 잔기를 인산화시켜 Src kinase의 활성을 저해한다. 이러한 Src-Csk loop를 통한 세포 내 신호전달과정은 세포의 증식과 분화, 사멸 조절에 중요한 기능을 갖지만 정소의 발생과 분화 과정에서 Src-Csk loop의 발현 및 정자형성 과정에서의 기능은 밝혀지지 않았다. 본 연구에서는 생쥐 정소에서 출생 후 성적 성숙과정에서 Csk의 발현과 Src kinase 활성의 변동을 조사하였다. Csk mRNA 발현은 생 후 2주령 이하의 미성숙 정소에서 다량으로 발현되었고 사춘기 정소 이후에는 오히려 감소하였다. Csk 단백질의 발현 양상은 mRNA 발현양상과 일치하였다. c-Src kinase 활성은 생 후 2주에 급격히 증가하고 이 후 4주령에서 감소하다가 성체 (8주령)에서 다시 증가하여 가장 높았다. 성체 조직의 Csk 단백질 현존량이 미성숙 개체보다 적은 반면 Src kinase 활성은 가장 높아 Csk 발현의 감소는 Src kinase 활성을 증가하는 것으로 사료된다. 면역조직화학방법으로 정소 조직 내 Csk의 발현양상을 조사한 결과 Leydig cell, Sertoli cell, germ cell 등 도처에서 발현되었으며 Sertoli cell 에서의 발현은 세정관 상피의 구성에 따른 차이가 확인되었다. 성체의 세정관 내에서는 감수분열 이후의 정세포(spermatid)를 감싸고 있는 Sertoli cell의 강소측에서 강한 Csk 활성이 검출되어 생식세포의 분화과정 동안 세정관 상피의 조직재구성에 관여하는 것으로 사료된다. Leydig cell에서의 발현은 생후 1주령까지는 미미하였으나 이후 2주령 이후에는 다량으로 발현함이 확인되어 adult type Leydig cell에서 진행되는 steroidogenesis와의 관련성을 추측할 수 있다. 미성숙 정소로부터 분리한 Sertoli cell-enriched culture에 200 nM testosterone을 처리하였을 때 Csk mRNA의 발현의 증가를 확인할 수 있었으므로 androgen에 의한 Sertoli cell의 분화과정에 Csk가 관여하고 있음을 알 수 있다. 결론적으로 성적 성숙에 따른 생쥐 정소 내 Src-Csk loop의 발현과 Src kinase 활성의 변동은 정소 내 간충조직, 세정관 상피의 증식 및 기능적 분화 과정을 매개하는 생리적 활성분자 수용체 하위의 신호전달 과정에 Src-Csk loop에 의한 조절가능성을 확인할 수 있었다.

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Seismic Performance Evaluation of SRC Composite Column using Direct Displacement Based Design Method (직접변위기반 설계법에 의한 SRC 합성기둥의 내진성능평가)

  • Jung, In-Kju;Park, Soon-Eung;Kim, Dong-Hyuk
    • Journal of Korean Association for Spatial Structures
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    • v.12 no.3
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    • pp.63-70
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    • 2012
  • In this study, the displacement-based design concept, the performance by the existing reinforced concerte column and steel reinforced concrete composite column for SRC purchased the maximum design ground acceleration improvement compared to the performance design. SRC have several advantages such as strength enhancement and high ductility. H-beam or steel tubes were used for embedded elements of the SRC composite columns. SRC cross-section for the P-M diagram and analysis on the nominal bending monent SRC designed for composite columns for disparity estimation is presented to the displacement-based seismic design. Performance improvement of the performance-based design performance targets for the design seismic displacement and design criteria for the direct displacement-based design methods and to improve the seismic performance due to the displacement coefficient method is proposed to design. SRC compared with the RC column designed to improve the performance and displacement ductility ratio displacement results in the performance design results showed significantly improved performance.

Strength Prediction of Spatially Reinforced Composites (공간적으로 보강된 복합재료의 강도예측)

  • 유재석;장영순;이상의;김천곤
    • Composites Research
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    • v.17 no.5
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    • pp.39-46
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    • 2004
  • In this study, the strength of spatially reinforced composites (SRC) are predicted by using stiffness reduction for each structural element composed of a rod stiffness in each direction and a matrix stiffness proportional to its rod volume fraction. Maximum failure strain criteria is applied to rod failure, and modified Tsai-Wu failure criteria to matrix failure. The material properties composed of the tensile failure strain of a rod, the compressive failure strain of 3D SRC, the tensile and compressive strength of the 3D SRC in the $45^{\cir}$ rotated direction from a rod and the shear strength of the 3D SRC are measured to predict the SRC strength. The strength distributions of the 3D/4D SRC in rod and off-rod direction have the largest and the smallest values, respectively. A variable load step is selected to increase an efficiency of strength distribution calculation. Uniform load step is applied when a load history is needed. The results of compressive strength from analysis and experiment show the 18 % difference though the initial slop is coincident with each other.

Comparative Analysis of Src Activity in Plasma Membrane Subdomains via Genetically Encoded FRET Biosensors (유전적으로 암호화된 FRET 바이오센서를 통한 세포막 하위 도메인의 Src 활성 비교 분석)

  • Gyuho Choi;Yoon-Kwan Jang;Jung-Soo Suh;Heonsu Kim;Sanghyun Ahn;Tae-Jin Kim
    • Journal of Life Science
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    • v.33 no.2
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    • pp.191-198
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    • 2023
  • As a member of the focal adhesion complex of the plasma membrane, Src is a nonreceptor tyrosine kinase that controls cell adhesion and motility. However, how Src activity is regulated in the plasma membrane microdomain in response to components of the extracellular matrix (ECM) remains unclear. This study compared and investigated the activity of Src in response to three representative ECM proteins: collagen type 1, fibronectin, and laminin. Genetically encoded FRET-based Src biosensors for plasma membrane subdomains were used. FRET-based biosensors allow the real-time analysis of protein activity in living cells based on their high spatiotemporal resolution. The results showed that Src activity was maintained at a high level under all ECM conditions of the lipid raft, and there was no significant difference between the ECM conditions. In contrast, Src activity was maintained at a low level in the non-lipid raft membrane. In addition, the Src activity of lipid rafts remained significantly higher than that of non-lipid raft regions under the same ECM conditions. In conclusion, this study demonstrates that Src activity can be controlled differently by lipid rafts and non-lipid raft microdomains.

Roles of Src-family kinase isoforms, Lyn, Fyn, Fgr, and c-Src on degranulation in RBL-2H3 mast cells (비만세포의 탈과립에 대한 다양한 Src-family kinase의 역할)

  • Lee, Jun-Ho;Mun, Se-Hwan;Ko, Na-Young;Kim, Jie-Wan;Kim, Do-Kyun;Kim, Joo-Dong;Her, Erk;Choi, Wahn-Soo
    • Journal of Life Science
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    • v.17 no.3 s.83
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    • pp.350-355
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    • 2007
  • The rat RBL-2H3 mast cells contain various Src-family kinases. Previous reports with this cell line indicated that Lyn activation is an important initial signaling for the activation of the cells. However, the role and location of other Src-family kinase isoforms which are expressed in the cells are not clear. In this study, we now show that isoforms of Src-family kinases, Lyn, fyn, Fgr, c-Src, and Yes are differentially expressed and located differently in the cells as indicated by RT-PCR, immunoblotting analysis, and confocal microscopy. Lyn and Fgr were located on plasma membrane but on the other hand c-Src and Yes were located on intracellular organelle. All of Src-family kinases were cloned and overexpressed for investigating the roles of the isoforms. Overexpression of Fyn and Fgr, not Lyn and c-Src, stimulated Ag-induced degranulation in the cells. Our findings strongly suggest for the first time that each of Src-family kinase isoform can regulate differentially $Fc{\varepsilon}RI$-mediated signaling in RBL-2H3 mast cells.

Column Shortening of SRC Columns Considering the Differential Moisture Distribution (부등수분분포를 고려한 SRC 기둥의 축소량에 관한 연구)

  • Seol, Hyun-Cheol;Kim, Yun-Yong;Kwon, Seung-Hee;Kim, Han-Soo;Kim, Jin-Keun
    • Journal of the Korea Concrete Institute
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    • v.18 no.1 s.91
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    • pp.29-36
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    • 2006
  • Steel reinforced concrete(SRC) columns, which have been widely employed in high-rise buildings, exhibit a time-dependent behavior because of creep and shrinkage of concrete. This long-term behavior may cause a serious serviceability problem in structural systems, so it is very important to predict the deformation due to creep and shrinkage of concrete. However, it was found from the previous experimental studies that the long-term deformation of SRC columns was quite dissimilar from that of RC columns. A new method is required to quantitatively predict the long-term deformation of SRC columns. In this study, the causes of the discrepancy between the behaviors of RC and SRC columns are investigated and discussed. SRC columns exhibit a time-dependent relative humidity distribution in a cross section differently from that of reinforced concrete(RC) columns owing to the presence of a inner steel plate, which interferes with the moisture diffusion of concrete. This relative humidity distribution may reduce the drying shrinkage and the drying creep in comparison with RC columns. Therefore it is suggested that the differential moisture distribution should be taken into account in order to reasonably predict column shortening of SRC columns.