Mechanisms for regulation of cell adhesion and migration
细胞粘附和迁移的调节机制
基本信息
- 批准号:8402394
- 负责人:
- 金额:$ 27.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-01-01 至 2014-12-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAdhesionsAffectAffinityBindingBinding ProteinsBiological ProcessCD47 AntigenCell AdhesionCell NucleusCell membraneCell-Cell AdhesionCellsCellular ImmunityComplementComplexCoupledCouplingCultured CellsCytoplasmic TailCytosolDataDefectDepositionDiseaseDisseminated Malignant NeoplasmDrosophila genusEmbryoEmbryonic DevelopmentEventExhibitsExtracellular MatrixGene ExpressionGoalsHumanHuman PathologyImmune responseInflammatory ResponseIntegrinsLHX1 geneLIM DomainLIMS1 geneLearningLeucine-Rich RepeatLocationMalignant - descriptorMalignant NeoplasmsMediatingMembraneMolecularMolecular Mechanisms of ActionNeoplasm MetastasisNeuronsNuclearNuclear ExportNuclear TranslocationOncogenicPhenotypePhosphotransferasesPlayPreventive InterventionProcessProtein BindingProtein Binding DomainProteinsRecruitment ActivityRegulationRegulatory PathwayRelative (related person)ResearchRoleScaffolding ProteinSeriesSignal PathwaySignal TransductionSiteSourceStimulusStructureTherapeutic InterventionTissuesTumor Cell InvasionWorkWound Healingcell motilitycohortgenetic regulatory proteininsightintegrin-linked kinaseinterestleucine-rich repeat proteinmigrationmutantnovelnull mutationras Oncogenereceptorresearch studyscaffoldtherapeutic targettumortumor progression
项目摘要
Project Summary
Regulated cell adhesion and migration are critical for a variety of biological processes including early
embryonic development, neuronal path-finding, inflammatory response, wound healing and tissue integrity,
cell-mediated immunity, and tumor invasion and metastasis. Integrin trans-membrane receptors are key
regulators of cell migration, and act through an intricate assembly of regulatory proteins associated with the
integrin cytoplasmic domain, many of which function as molecular scaffolds. The goal of this research is to
identify novel regulatory pathways by which scaffolding proteins modulate cell adhesion and migration via
regulated binding of protein partners. In previous work, we characterized the LIM domain scaffold PINCH,
which is required for integrin-dependent cell adhesion, migration and signaling. PINCH binds with high affinity
to both Integrin-linked kinase (ILK) and Ras suppressor 1 (RSU1), a Leucine-rich repeat protein that
suppresses transformation of cultured cells expressing activated Ras, an oncogene present in 30% of all
human tumors. We propose that the PINCH scaffold serves as a node for modulating integrin signaling by
regulated recruitment of partners like ILK and RSU1, coupled to other signaling pathways.
Through a series of experiments in Drosophila in which we specifically disrupt binding interactions with
PINCH and alter the subcellular localization of components of the PINCH complex, we will dissect the
requirement for ILK and RSU1 binding in carrying out the integrin-dependent functions of PINCH. Our
preliminary data indicates that binding to ILK localizes PINCH within integrin-associated complexes at the cell
membrane, and regulates the shuttling of PINCH to the nucleus. We will determine if PINCH has essential
functions in the nucleus, and whether it has an overlapping complement of binding partners in the cytosol
versus the nucleus. Additional data suggest that RSU1 is sequestered in integrin-associated complexes by its
interaction with PINCH. We will examine how PINCH-RSU1 binding is regulated, and identify partners and
activities for RSU1 that are independent of PINCH.
A molecular understanding of how PINCH regulates cell adhesion and migration through its scaffolding
activity may ultimately suggest strategies for prevention and therapeutic intervention in human pathologies like
metastatic cancer, in which aberrant cell migration plays a prominent role.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JULIE L KADRMAS其他文献
JULIE L KADRMAS的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JULIE L KADRMAS', 18)}}的其他基金
Mechanisms for regulation of cell adhesion and migration
细胞粘附和迁移的调节机制
- 批准号:
8017474 - 财政年份:2009
- 资助金额:
$ 27.05万 - 项目类别:
Mechanisms for regulation of cell adhesion and migration
细胞粘附和迁移的调节机制
- 批准号:
7753888 - 财政年份:2009
- 资助金额:
$ 27.05万 - 项目类别:
Mechanisms for regulation of cell adhesion and migration
细胞粘附和迁移的调节机制
- 批准号:
8208127 - 财政年份:2009
- 资助金额:
$ 27.05万 - 项目类别:
PROTEIN PROTEIN INTERACTIONS IN POLYISOPRENE SYNTHESIS
聚异戊二烯合成中的蛋白质相互作用
- 批准号:
6178856 - 财政年份:2000
- 资助金额:
$ 27.05万 - 项目类别:
PROTEIN PROTEIN INTERACTIONS IN POLYISOPRENE SYNTHESIS
聚异戊二烯合成中的蛋白质相互作用
- 批准号:
6018436 - 财政年份:1999
- 资助金额:
$ 27.05万 - 项目类别:
PROTEIN PROTEIN INTERACTIONS IN POLYISOPRENE SYNTHESIS
聚异戊二烯合成中的蛋白质相互作用
- 批准号:
2710098 - 财政年份:1999
- 资助金额:
$ 27.05万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 27.05万 - 项目类别:
Research Grant