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      Roles of Src-family kinase isoforms, Lyn, Fyn, Fgr, and c-Src on degranulation in RBL-2H3 mast cells

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      https://www.riss.kr/link?id=A103837328

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      국문 초록 (Abstract)

      흰쥐유래의 비만세포인 RBL-2H3 세포는 다양한 Src-family kinase를 발현한다. 현재까지의 연구결과에 의하면 비만세포의 초기 활성화에 Lyn kinase가 중요한 역할을 한다고 알려져 왔다. 그러나 그 ...

      흰쥐유래의 비만세포인 RBL-2H3 세포는 다양한 Src-family kinase를 발현한다. 현재까지의 연구결과에 의하면 비만세포의 초기 활성화에 Lyn kinase가 중요한 역할을 한다고 알려져 왔다. 그러나 그 세포에서 발현되는 다양한 다른 Src-family kinase의 역할은 불분명하다. 본 연구에서는 비만세포에서 다양한 Src-family kinase가 세포내 다른 곳에서 다양하게 발현되고 있다는 사실을 RT-PCR, immunoblotting 그리고 confocal microscopy 기법을 이용하여 증명하였다. 그 결과 Lyn 및 Fgr kinase는 세포막에 위치하고 c-Src 및 Yes kinase는 세포 내 과립에 존재하는 것을 알 수 있었다. 모든 Src-family kinase를 클로닝하고 과발현하여 탈과립 대한 영향을 평가하였다. 그 결과 fyn과 Fgr kinase는 비만세포에서 항원 유도의 탈과립을 증가시켰으며 반면 Lyn kinsae는 탈과립을 억제시키는 것을 확인할 수 있었다. 이러한 결과는 비만세포 초기 신호전달계에서 Fgr가 중요한 역할을 할 가능성을 제시한다.

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      다국어 초록 (Multilingual Abstract)

      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 kin...

      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.

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      참고문헌 (Reference)

      1 Cissel, D. S., "Thapsigargin-induced secretion is dependent on activation of a cholera toxin-sensitive and a phosphatidylinositol-3-kinase-regulated phospholipase D in a mast cell line" 285 : 110-118, 1998

      2 Kovarova, M., "Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation" 21 : 8318-8328, 2001

      3 Turner, H., "Signaling through the high affinity IgE receptor FcεRI" 402 : B24-B30, 1999

      4 Wedemeyer, J., "Roles of mast cells and basophils in innate and acquired immunity" 12 : 624-631, 2000

      5 Kawakami, Y., "Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation" 165 : 1210-1219, 2000

      6 Xiao, W., "Positive and negative regulation of mast cells activation by Lyn via the FcεRI" 175 : 6885-6892, 2005

      7 Brown, F. D., "Phospholipase D1 localizes to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulation" 8 : 835-838, 1998

      8 El Shazly, A., "Novel association of the SFKs, hck and c-fgr, with CCR3 receptor stimulation: a possible mechanism for eotaxin-induced human eosinophil chemotaxis" 264 : 163-170, 1999

      9 Gresham, H. D., "Negative regulation of phagocytosis in murine macrophages by the Src kinase family member" 191 : 515-528, 2000

      10 Odom, S., "Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase" 199 : 1491-1502, 2004

      1 Cissel, D. S., "Thapsigargin-induced secretion is dependent on activation of a cholera toxin-sensitive and a phosphatidylinositol-3-kinase-regulated phospholipase D in a mast cell line" 285 : 110-118, 1998

      2 Kovarova, M., "Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation" 21 : 8318-8328, 2001

      3 Turner, H., "Signaling through the high affinity IgE receptor FcεRI" 402 : B24-B30, 1999

      4 Wedemeyer, J., "Roles of mast cells and basophils in innate and acquired immunity" 12 : 624-631, 2000

      5 Kawakami, Y., "Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation" 165 : 1210-1219, 2000

      6 Xiao, W., "Positive and negative regulation of mast cells activation by Lyn via the FcεRI" 175 : 6885-6892, 2005

      7 Brown, F. D., "Phospholipase D1 localizes to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulation" 8 : 835-838, 1998

      8 El Shazly, A., "Novel association of the SFKs, hck and c-fgr, with CCR3 receptor stimulation: a possible mechanism for eotaxin-induced human eosinophil chemotaxis" 264 : 163-170, 1999

      9 Gresham, H. D., "Negative regulation of phagocytosis in murine macrophages by the Src kinase family member" 191 : 515-528, 2000

      10 Odom, S., "Negative regulation of immunoglobulin E-dependent allergic responses by Lyn kinase" 199 : 1491-1502, 2004

      11 Hibbs, M. L., "Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease" 83 : 301-311, 1995

      12 Rivera, J., "Molecular adapters in FcRI signaling and the allergic response" 14 : 688-693, 2002

      13 Beaven, M. A, "Mast cell related diseases: genetics, signaling pathways, and novel therapies, In Signal transduction and human disease" John Wiley & Sons, Inc. 307-355, 2003

      14 Xu, Y., "Lyntyrosine kinase: accentuating the positive and the negative" 22 : 9-18, 2005

      15 Saitoh, S., "LAT is essential for FcεRI-mediated mast cell activation" 12 : 525-535, 2000

      16 Nishizumi, H., "Impaired tyrosine phosphorylation and Ca2+ mobilization, but not degranulation, in lyn-deficient bone marrow-derived mast cells" 158 : 2350-2355, 1997

      17 Suen, P. W., "Impaired integrin- mediated signal transduction, altered cytoskeletal structure and reduced motility in Hck/Fgr deficient macrophages" 112 : 4067-4078, 1999

      18 Seldin, D. C., "Homology of the rat basophilic leukemia cell and the rat mucosal mast cell" 82 : 3871-3875, 1985

      19 Wilson, B. S., "High resolution mapping of mast cell membranes reveals primary and secondary domains of FcRI and LAT" 154 : 645-658, 2001

      20 Parravinci, V., "Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation" 3 : 741-748, 2002

      21 Vicentini, L., "Fgr deficiency results in defective eosinophil recruitment to the lung during allergic airway inflammation" 168 : 6446-6454, 2002

      22 Gu, H., "Essential role for Gab2 in the allergic response" 412 : 186-190, 2001

      23 Mocsai, A., "Adhesion-dependent degranulation of neutrophils requires the SFKs Fgr and Hck" 162 : 1120-1126, 1999

      24 Way, G., "Activation of exocytosis by cross-linking of the IgE receptor is dependent on ADP-ribosylation factor 1-regulated phospholipase D in RBL-2H3 mast cells: evidence that the mechanism of activation is via regulation of phosphatidylinositol 4,5-bisphosphate synthesis" 346 : 63-70, 2000

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-08-03 학술지명변경 외국어명 : Korean Journal of Life Science -> Journal of Life Science KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2007-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2004-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2003-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2001-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보

      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.37 0.37 0.42
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.43 0.43 0.774 0.09
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