초록

Wnt 신호전달과정에서 cell surface에서 일어나는 Wnt 신호 전달 조절을 이해하기위해 다양한 Frizzled4, Kremen1등의 다양한 수용체와 Wnt5a, DKK1등의 다양한 분비 단백질을 발현 및 정제하고 이들을 결정화하고 3차 구조를 밝히기 위해 노력함. 이에 Frizzled4 CRD 3차구조를 밝혔으며, Frizzled4와 Wnt5a의 복합체 형성에 성공함. 그리고 DKK1, Kremen1을 정제하고 복합체를 형성했으며 결정화에 성공함.

Abstract ▼

Given the fact that aberrant activation of the Wnt signaling pathway is linked to not only tumor initiation but also tumor progression, it has been an intensively-studied target for cancer therapeutic intervention since the late 1990s. Recent reports show that DKK1/Kremen1/LRP5 inhibitory complex ma

Given the fact that aberrant activation of the Wnt signaling pathway is linked to not only tumor initiation but also tumor progression, it has been an intensively-studied target for cancer therapeutic intervention since the late 1990s. Recent reports show that DKK1/Kremen1/LRP5 inhibitory complex may be good candidates for fighting certain types of cancer. In this application, I propose an ambitious new initiative of elucidating the molecular mechanisms of Wnt signaling regulation at the cell surface. In order to manipulate Wnt signaling, the molecular mechanisms underlying this pathway first have to be understood. As cell surface receptors continue to be the targets of choice for drug development given their accessibility to drugs and their role as the initiating event for signaling, this structural information is a necessary step toward chemical modulation.
1. We Made various constructs of Lrp5, DKK, Kremen and perform expression test using a "Bacmam system" , "Insect cell system" , "E.coli expression system" .
2. We expressed and purified LRP5, DKK1, and Kremen1 protein
3. We reconstituted DKK/Kremen complex in vitro. We also biochemically determine the interaction region of Kremen to DKK by binding mapping studies.
4. We also analized the interaction b/w DKK1 and Kremen1.
5. We crystalized Kremen1 and DKK1/Kremen1 binary complex

목차 Contents

• 1. 표지 ...1
• 2. 제출문 ...3
• 3. 보고서 요약서 ...4
• 4. 요약문(한글) ...5
• 5. 요약문(영문) ...6
• 6. 연구 성과 실적 및 향후 계획 ...7
• 7. 참여연구원 현황표 ...11
• I. 총괄연구과제 연구결과 ...12
• 1. 연구개발과제의 배경 및 필요성 ...13
• 2. 국내외 기술개발 현황 ...14
• 3. 연구개발과제의 추진체계 ...16
• 4. 연구개발수행 내용 및 결과 ...17
• 5. 목표달성도 및 관련분야 기여도 ...26
• 6. 향후 연구성과 추진 계획(※해당되는 경우만 작성) ...28
• 7. 연구개발결과의 파급효과 ...28
• 8. 연구개발결과의 활용계획 ...29
• 9. 연구개발과정에서 수집한 해외과학기술정보 ...29
• 10. 참고문헌 ...29
• II. 첨부서류 ...31
• 목차 ...32
• 1. 자체평가의견서 ...32
• 2. 실적 증빙자료 ...37
• 3. 기타 첨부서류 ...49