FUNCTIONAL STUDIES OF FOCAL ADHESION KINASE
粘着斑激酶的功能研究
基本信息
- 批准号:6329746
- 负责人:
- 金额:$ 26.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-12-01 至 2002-06-30
- 项目状态:已结题
- 来源:
- 关键词:animal tissue biological signal transduction cell migration enzyme activity enzyme induction /repression extracellular matrix fibroblasts focal adhesion kinase gene mutation genetic mapping integrins laboratory mouse monoclonal antibody phosphorylation protein structure serine tissue /cell culture tyrosine
项目摘要
DESCRIPTION: Integrin-mediated adhesion to the extracellular matrix (ECM)
profoundly affect cell shape, motility, survival, proliferation, and
differentiation. These behavioral properties are critical for normal growth
and development, and impact upon many human pathological processes including
tumor growth and metastasis, atherogenesis, thrombosis and hemostasis,
inflammation, and cutaneous wound repair. The broad long-term objective of
this project is to understand the biochemical signaling mechanisms by which
ligand-engaged integrins influence cell behavior, thereby revealing new
therapeutic targets for the treatment of adhesion-influenced disease
processes. The three specific aims address the general hypothesis that the
focal adhesion tyrosine kinase "FAK" is a key signaling molecule affecting
integrin-mediated changes in cell behavior. Aim 1 will determine the
regulatory mechanisms involved in a FAK-enhanced cell migration response.
The effect of inducible FAK expression on the ability of cells to migrate
toward defined serum components in a Boyden assay will be assessed, and the
FAK functional properties required for the response will be examined by
measuring migration rates of cells expressing FAK mutants deficient in
specific signaling activities. Aim 2 will examine the role of FAK kinase
domain activation loop phosphorylation in integrin signaling responses. The
mechanism of FAK activation will be defined by determining the ability of
mutant FAK variants, deficient in either activation loop phosphorylation or
interactions with Src family kinases, to become fully phosphorylated and
catalytically active in response to call adhesion. Monoclonal antibodies
that specifically recognize the phosphorylated FAK activation loop will be
employed to reveal the dynamics and regionalization of activated FAK during
the course of cell spreading and migration. Aim 3 will examine the role of
serine phosphorylation on FAK's signaling properties and adhesion-stimulated
cellular responses. The major site of FAK serine phosphorylation in
adherent fibroblasts will be determined by a phosphopeptide mapping
strategy, and the potential role of this phosphorylation event in regulating
FAK's signaling capacity and functional properties will be assessed through
expression and analysis of the phosphoaccentor serine FAK mutant.
描述:整合素介导的细胞外基质(ECM)粘附
深刻影响细胞形状、运动性、存活、增殖,
分化 这些行为特性对正常生长至关重要
和发展,并影响许多人类病理过程,包括
肿瘤生长和转移、动脉粥样硬化形成、血栓形成和止血,
炎症和皮肤伤口修复。 长远的目标,
这个项目是为了了解生物化学信号机制,
配体参与的整合素影响细胞行为,从而揭示了新的
用于治疗粘连影响的疾病的治疗靶点
流程. 这三个具体目标涉及的一般假设是,
粘着斑酪氨酸激酶“FAK”是影响粘附的关键信号分子,
整合素介导的细胞行为变化。 目标1将决定
参与FAK增强的细胞迁移反应的调节机制。
诱导型FAK表达对细胞迁移能力的影响
将评估Boyden测定中定义的血清组分,
响应所需的FAK功能特性将由
测量表达FAK突变体的细胞的迁移速率,所述FAK突变体在
具体的信号活动。 目的2将研究FAK激酶的作用
整合素信号应答中的结构域激活环磷酸化。 的
FAK激活的机制将通过确定
突变型FAK变体,缺乏活化环磷酸化或
与Src家族激酶相互作用,完全磷酸化,
响应呼叫粘附的催化活性。 单克隆抗体
特异性识别磷酸化FAK激活环的细胞
用于揭示激活FAK的动态和区域化,
细胞扩散和迁移的过程。 目标3将审查
丝氨酸磷酸化对FAK信号传导特性和粘附刺激的影响
细胞反应。 FAK丝氨酸磷酸化的主要位点在
粘附成纤维细胞将通过磷酸肽图谱确定
策略,以及这种磷酸化事件在调节
FAK的信号传导能力和功能特性将通过
磷酸accentor丝氨酸FAK突变体的表达和分析。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Steven K. Hanks其他文献
Chromatin structure during the prereplicative phases in the life cycle of mammalian cells
- DOI:
10.1007/bf02785097 - 发表时间:
1980-12-01 - 期刊:
- 影响因子:2.500
- 作者:
Potu N. Rao;Steven K. Hanks - 通讯作者:
Steven K. Hanks
Steven K. Hanks的其他文献
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{{ truncateString('Steven K. Hanks', 18)}}的其他基金
FAK/Src/CAS Signaling in Cell Motility and Invasion
细胞运动和侵袭中的 FAK/Src/CAS 信号转导
- 批准号:
7907309 - 财政年份:2009
- 资助金额:
$ 26.65万 - 项目类别:
PATHOGENESIS OF FAMILIAL JUVENILE NEPHRONOPHTHISIS
家族性青少年肾病的发病机制
- 批准号:
6635170 - 财政年份:2000
- 资助金额:
$ 26.65万 - 项目类别:
PATHOGENESIS OF FAMILIAL JUVENILE NEPHRONOPHTHISIS
家族性青少年肾病的发病机制
- 批准号:
6517623 - 财政年份:2000
- 资助金额:
$ 26.65万 - 项目类别:
PATHOGENESIS OF FAMILIAL JUVENILE NEPHRONOPHTHISIS
家族性青少年肾病的发病机制
- 批准号:
6381565 - 财政年份:2000
- 资助金额:
$ 26.65万 - 项目类别:
PATHOGENESIS OF FAMILIAL JUVENILE NEPHRONOPHTHISIS
家族性青少年肾病的发病机制
- 批准号:
6095250 - 财政年份:2000
- 资助金额:
$ 26.65万 - 项目类别:
FAK/Src/CAS Signaling in Cell Motility and Invasion
细胞运动和侵袭中的 FAK/Src/CAS 信号转导
- 批准号:
7365069 - 财政年份:1994
- 资助金额:
$ 26.65万 - 项目类别:
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