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dc.contributor.advisor이종란-
dc.contributor.author유미진-
dc.creator유미진-
dc.date.accessioned2017-08-27T11:08:02Z-
dc.date.available2017-08-27T11:08:02Z-
dc.date.issued2017-
dc.identifier.otherOAK-000000138456-
dc.identifier.urihttp://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000138456en_US
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/235989-
dc.description.abstractARAP (activation-dependent, raft-recruited ADAP-like phosphoprotein)은 항원 수용체 자극 후 세포막의 raft 층으로 이동하여 T 세포 활성화에 관여하는 새로운 단백질로 보고되었다. 생체 내에서 ARAP의 기능을 연구하기 위해 ARAP 결핍 마우스를 사용하였고 이전 연구에서 ARAP이 결핍 된 마우스의 T 세포에서 초기신호전달이 제대로 일어나지 않는 것을 확인하였다. 본 연구에서는 초기신호전달에서 ARAP의 기능을 추가 적으로 규명하기 위해 B 세포와 T 세포의 초기신호전달에 관여하는 단백질의 티로신 인산화를 확인하였다. ARAP은 T 세포뿐만 아니라 B 세포의 초기활성화에도 관여 할 수 있음을 보여 주었다. 또한, T 세포의 많은 신호 분자가 대식세포 및 수지상 세포에 존재하기 때문에 이들 세포에서 ARAP의 기능을 살펴보았다. ARAP이 결핍 된 마우스의 대식세포와 수지상 세포는 LPS에 의해 활성화되었을 때 식세포 기능과 세포의 이동, 액틴 중합 및 사이토 카인 생성이 유의하게 감소된 것을 확인하였다. 종합적으로, 이 연구에서의 결과는 ARAP이 T 및 B 세포, 대식세포 및 수상 세포의 활성화 신호 전달 사건에 대해 조절되는 중요한 adaptor 단백질이라는 것을 강력히 시사한다.;ARAP (activation-dependent, raft-recruited ADAP-like phosphoprotein) has been reported as a novel protein, which is recruited to the membrane raft and is involved in T cell activation after antigen receptor stimulation. To study the function of ARAP in vivo, ARAP-deficient mice were generated. Previous studies in our laboratory showed that initial activation signaling events were defective in T cells from ARAP-deficient mice. In this study, further characterization of ARAP function in an initial event, protein tyrosine phosphorylation was performed in T and B cells. Similarly to T cells, ARAP-deficient B cells were decreased tyrosine phosphorylation. The results showed that ARAP may also function in the initial B cell activation. In addition, the function of ARAP was examined in macrophages and dendritic cells because many signaling molecules of T cells also function in these cells. Phagocytic function, migration, actin polymerization, and cytokine production were compared in LPS-activated macrophages and dendritic cells from ARAP WT and KO mice. The results showed that these functions of macrophages and dendritic cells after LPS stimulation were significantly reduced in the absence of ARAP. Collectively, the results in this study strongly indicate that ARAP is an important adapter protein that is regulated for the activation signaling events in T and B cells, macrophages, and dendritic cells, although the details how ARAP functions in each signaling pathway remain to be studied.-
dc.description.tableofcontentsⅠ. Introduction 1 Ⅱ. Materials and methods 9 1. Mice 9 2. Cell isolation and culture 9 3. Stimulation of T and B cells and western blotting 10 4. RT-PCR 11 5. Phagocytosis assays 12 6. Migration Assay 12 7. Actin polymerization 13 8. Cytokine assay 13 9. Flow cytometry 13 10. Statistical analysis 14 Ⅲ. Results 15 1. Expression of ARAP 15 2. Functional analysis of ARAP in the initial signaling of T and B cell activation 15 3. Functional analysis of ARAP in LPS-activated macrophages 19 4. Functional analysis of ARAP in LPS-activated dendritic cells 25 Ⅳ. Discussion 32 Ⅴ. References 35 Ⅵ. Abstract (in Korean) 39-
dc.formatapplication/pdf-
dc.format.extent2030148 bytes-
dc.languageeng-
dc.publisher이화여자대학교 대학원-
dc.subject.ddc600-
dc.titleFunctional characterization of a novel adaptor protein, ARAP, in immune cells-
dc.typeMaster's Thesis-
dc.format.pageix, 39 p.-
dc.identifier.thesisdegreeMaster-
dc.identifier.major대학원 생명과학과-
dc.date.awarded2017. 2-
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