ASTACIN PROTEASES, TFG-SIGNALING & EXTRACELLULAR MATRIX

虾红素蛋白酶、TFG 信号传导

• 批准号: 6325796
• 负责人: ERIC W HOWARD
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325796
• 关键词: ASTACIN; PROTEASES; TFG; SIGNALING; EXTRACELLULAR

Establishing a Link between Astacin Proteases. TGF-Beta Signaling and the Extracellular Matrix. A major theme has evolved from our understanding of diverse biological systems. Namely, that the conservation of molecules among species as disparate as fruit flies and humans allows us to evaluate signaling pathways in one with the strong possibility that similar regulatory mechanisms are common to both. This has in fact been the case for factors in a highly complex and strictly conserved BMP signaling pathway. Members of the astacin family of metalloproteases are proposed to act in this pathway by directly targeting molecules that antagonize BMP signaling and therefore represent a pivotal level of regulation. Our work is designed to understand the role of the astacin protease SpAN from the sea urchin, Strongylocentrotus purpuratus, (1) in normal development and (II) In regulating BMP signaling in other developmental systems. I) While the pattern and regulation of SpAN gene expression has been studied extensively, the developmental expression and biochemical activity of the SpAN protease has not been characterized. I have developed a polyclonal antisera generated against SpAN and localized expression of the protease to the apical side of developing blastulae. In order to understand SpAN's role in morphogenesis, we propose methods to disrupt SpAN activity in vivo and to isolate possible biochemical target(s). II) Related astacin proteases. Including a large family of Tolloid molecules from vertebrates and Drosophila, play an important role in pattern formation and are thought to act by enhancing BMP signaling. We provide a biochemical explanation for SpAN activity in this pathway as the BMP antagonist Chordin is cleaved by SpAN in an in vitro assay. In addition to their role in early development, BMPs are potent osteo-genic agents. We will test, directly, SpAN's ability to modulate bone growth in a rat mandible defect model. Key Words: Astacin protease, TGF Beta-Bone morphogenetic protein, Signaling, extracellular matrix, sea urchin

建立Astacin蛋白酶之间的联系。 TGF-β信号传导和 细胞外基质 一个主要的主题是从我们对各种生物学的理解中演变出来的， 系统. 也就是说，物种之间的分子守恒， 不同的果蝇和人类让我们能够评估信号 在一个很大的可能性，类似的调节途径， 两者的机制是相同的。 事实上， 高度复杂和严格保守的BMP信号传导中的因子 通路 提出了金属蛋白酶的astacin家族的成员， 通过直接靶向拮抗 BMP信号传导，因此代表了调节的关键水平。 我们的工作旨在了解的作用，astacin蛋白酶SpAN 从海胆，球海胆，（1）在正常 （二）在其他发育过程中调节BMP信号 系统. I）虽然SpAN基因表达的模式和调控已经被证实是一种新的基因表达模式， 广泛研究，发育表达和生化 SpAN蛋白酶的活性尚未被表征。 我有 开发了一种针对SpAN的多克隆抗血清， 蛋白酶表达到发育囊胚的顶侧。 为了理解SpAN在形态发生中的作用，我们提出了一些方法， 破坏体内SpAN活性并分离可能的生化物质 目标。 II）相关的astacin蛋白酶。 包括一个庞大的托洛德家族 脊椎动物和果蝇的分子，在 模式形成，并认为通过增强BMP信号传导起作用。 我们 为SpAN在该途径中的活性提供了生物化学解释， BMP拮抗剂Chordin在体外测定中被SpAN切割。 在 除了在早期发育中的作用外，BMP还具有强有力的成骨作用， 剂. 我们将直接测试SpAN调节骨生长的能力 在大鼠下颌骨缺损模型中。 关键词：Astacin蛋白酶，TGF β-骨形态发生蛋白， 信号传导，细胞外基质，海胆