서브메뉴
검색
How to Compartmentalize Signaling: Lipids, Hedgehog, and Ciliary PKA
How to Compartmentalize Signaling: Lipids, Hedgehog, and Ciliary PKA
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202104807
- ISBN
- 9798293851447
- DDC
- 574
- 저자명
- Nguyen, Thi Dan.
- 서명/저자
- How to Compartmentalize Signaling: Lipids, Hedgehog, and Ciliary PKA
- 발행사항
- [Sl] : University of California, San Francisco, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 127 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Reiter, Jeremy;Selleri, Licia.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2025.
- 초록/해제
- 요약Cells coordinate nearly countless numbers of signaling reactions within them at any given time. To distinguish between different signaling inputs and outputs, cells utilize spatially compartmentalized signaling hubs to regulate their biochemical processes. We review how the primary cilium, an organelle specialized in intracellular signaling, utilizes lipids to create a specialized microenvironment. Hedgehog (HH) signaling in vertebrates is dependent on the primary cilium, an organelle that scaffolds signal transduction. HH signals induce Smoothened (SMO) enrichment in the cilium and indirectly triggers the conversion of GLI proteins into transcriptional activators of HH target genes. Recently, SMO has been shown to inhibit protein kinase A (PKA). To test the hypothesis that SMO specifically inhibits PKA at cilia to activate the HH signal transduction pathway, we developed a ciliary PKA biosensor. Activation of the HH signal transduction pathway by either Sonic hedgehog (SHH) or SMO agonist (SAG) inhibited ciliary PKA activity. Blocking SMO phosphorylation by GRK2/3 prevented ciliary SMO from inhibiting ciliary PKA activity. Gai/o was dispensable for SMO inhibition of ciliary PKA. In contrast, mutating the SMO C-terminal tail protein kinase inhibitor (PKI) pseudosubstrate site interfered with the ability of SMO to inhibit ciliary PKA. Therefore, HH signaling is transduced via SMO direct inhibition of PKA at cilia, in a manner dependent on GRK2/3.
- 일반주제명
- Biochemistry
- 일반주제명
- Developmental biology
- 일반주제명
- Cellular biology
- 일반주제명
- Biology
- 키워드
- Biosensor design
- 키워드
- Ciliary PKA
- 키워드
- Lipids
- 키워드
- Protein kinase A
- 키워드
- Smoothened
- 기타저자
- University of California, San Francisco Developmental and Stem Cell Biology
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2025 us c eng d■001000017358900
■00520260202104807
■006m o d
■007cr#unu||||||||
■020 ▼a9798293851447
■035 ▼a(MiAaPQ)AAI32165999
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aNguyen, Thi Dan.▼0(orcid)0000-0001-7525-920X
■24510▼aHow to Compartmentalize Signaling: Lipids, Hedgehog, and Ciliary PKA
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a127 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Reiter, Jeremy;Selleri, Licia.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2025.
■520 ▼aCells coordinate nearly countless numbers of signaling reactions within them at any given time. To distinguish between different signaling inputs and outputs, cells utilize spatially compartmentalized signaling hubs to regulate their biochemical processes. We review how the primary cilium, an organelle specialized in intracellular signaling, utilizes lipids to create a specialized microenvironment. Hedgehog (HH) signaling in vertebrates is dependent on the primary cilium, an organelle that scaffolds signal transduction. HH signals induce Smoothened (SMO) enrichment in the cilium and indirectly triggers the conversion of GLI proteins into transcriptional activators of HH target genes. Recently, SMO has been shown to inhibit protein kinase A (PKA). To test the hypothesis that SMO specifically inhibits PKA at cilia to activate the HH signal transduction pathway, we developed a ciliary PKA biosensor. Activation of the HH signal transduction pathway by either Sonic hedgehog (SHH) or SMO agonist (SAG) inhibited ciliary PKA activity. Blocking SMO phosphorylation by GRK2/3 prevented ciliary SMO from inhibiting ciliary PKA activity. Gai/o was dispensable for SMO inhibition of ciliary PKA. In contrast, mutating the SMO C-terminal tail protein kinase inhibitor (PKI) pseudosubstrate site interfered with the ability of SMO to inhibit ciliary PKA. Therefore, HH signaling is transduced via SMO direct inhibition of PKA at cilia, in a manner dependent on GRK2/3.
■590 ▼aSchool code: 0034.
■650 4▼aBiochemistry
■650 4▼aDevelopmental biology
■650 4▼aCellular biology
■650 4▼aBiology
■653 ▼aBiosensor design
■653 ▼aCiliary PKA
■653 ▼aHedgehog signaling
■653 ▼aLipids
■653 ▼aProtein kinase A
■653 ▼aSmoothened
■690 ▼a0487
■690 ▼a0758
■690 ▼a0379
■690 ▼a0306
■71020▼aUniversity of California, San Francisco▼bDevelopmental and Stem Cell Biology.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358900▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
