Full metadata record
DC Field | Value | Language |
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dc.contributor.advisor | 이수영 | - |
dc.contributor.author | 노지연 | - |
dc.creator | 노지연 | - |
dc.date.accessioned | 2016-08-26T12:08:34Z | - |
dc.date.available | 2016-08-26T12:08:34Z | - |
dc.date.issued | 2012 | - |
dc.identifier.other | OAK-000000070142 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/190267 | - |
dc.identifier.uri | http://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000070142 | - |
dc.description.abstract | PTEN (Phosphatase and tensin homolog deleted on chromosome ten) 은 lipid second messenger를 탈인산화 시키는 인지질 탈인산화 효소 (lipid phosphatase) 로 PI3K/Akt 신호전달 경로를 저해함으로써 세포의 이동, 세포자연사 (apoptosis), 세포 주기 (cell cycle) 등 다양한 세포의 활동을 조절한다. 최근의 연구를 통해서 PTEN이 파골세포 (Osteoclast) 의 분화에도 관여한다는 사실이 알려졌다. PTEN은 다양한 인산화 site를 가지고 있는데, 이 중 앞선 연구에서 파골세포 분화를 억제하는 기능이 밝혀진 GSK (Glycogen synthase kinase) -3β에 의해 인산화되는 site인 Serine 362와 Threonine 366을 Alanine으로 치환하여 인산화 활성이 억제된 돌연변이들을 만들었다. 이 돌연변이들을 과발현하거나 GSK-3β억제제를 사용해 GSK-3β의 활성을 억제한 세포에서는 PTEN의 탈인산화 효소 활성이 감소하고, 이 돌연변이들이 과발현 된 BMM (Bone marrow macrophage) 에서는 파골세포의 분화가 촉진된다는 것을 확인하였다. 이러한 결과들은 GSK3에 의한 PTEN의 인산화가 파골세포 분화 과정에서 중요한 역할을 가짐을 시사한다. ;Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a lipid phosphatase, which dephosphorylates the lipid second messenger, and antagonizes the PI3K/Akt signaling pathway. Therefore PTEN regulates various cellular processes including cell cycle, migration and apoptosis. Recently, it has been known that PTEN regulates RANKL-mediated osteoclast differentiation. In this study, we examined how PTEN affects the osteoclast differentiation through its phosphorylation by GSK-3β. PTEN contains multiple putative phosphorylation sites. Among them, GSK-3β phosphorylates PTEN at S362 and T366 sites. We made phosphorylation-deficient mutants of GSK-3β by converting serine and threonine to alanine. These mutants showed defect of phosphatase activity in comparison with wild type PTEN. Consistently, treatment of GSK-3β inhibitor diminished the level of PTEN phosphatase activity in a dose-dependent manner. Our data suggested that phosphorylation of PTEN by GSK-3β may have essential role in osteoclast differentiation. | - |
dc.description.tableofcontents | Ⅰ INTRODUCTION 1 Ⅱ EXPERIMENTAL PROCEDURES 5 1. Cell culture and reagent 5 2. Construction of mutants and mutagenesis 5 3. PTEN phosphatase activity assay 6 4. Transfection of 293T cells 7 5. SiRNA transfection in BMMs 7 6. Retroviral infection in BMMs 8 7. Osteoclasts formation assay 8 8. Western blotting and antibodies 9 Ⅲ RESULTS 11 1. GSK-3β phosphorylates PTEN 11 2. GSK-3β regulates Akt activation through PTEN phosphorylation 13 3. Phosphorylation of PTEN by GSK-3β is important for its phosphatase activity 16 4. PTEN negatively regulates osteoclasts differentiation through inactivation of Akt. 20 5. Phosphorylation of PTEN by GSK-3β has significant affect osteoclasts differentiation 24 Ⅳ DISCUSSION 28 Ⅴ. REFERENCES 30 Ⅵ. 논문개요 34 | - |
dc.format | application/pdf | - |
dc.format.extent | 5504730 bytes | - |
dc.language | eng | - |
dc.publisher | 이화여자대학교 대학원 | - |
dc.title | The role of PTEN in the osteoclast differentiation | - |
dc.type | Master's Thesis | - |
dc.title.translated | 파골세포 분화에 미치는 PTEN의 역할 | - |
dc.format.page | iv, 35 p. | - |
dc.identifier.thesisdegree | Master | - |
dc.identifier.major | 대학원 바이오융합과학과 | - |
dc.date.awarded | 2012. 2 | - |