ASTACIN PROTEASES, TFG-SIGNALING & EXTRACELLULAR MATRIX

在阿斯塔蛋白水解酶之间建立联系。转化生长因子-β信号转导和 细胞外基质。 一个主要的主题是从我们对不同生物的理解中演变出来的 系统。也就是说，物种间分子的守恒就像 不同的果蝇和人类允许我们评估信号 有很大可能类似的监管 这两种机制是共同的。事实上，情况就是这样 高度复杂和严格保守的BMP信号中的因素 路径。提出了ASTIN金属蛋白水解酶家族成员 通过直接针对拮抗分子在这一途径中发挥作用 BMP信号转导，因此代表了一个关键的调控水平。 我们的工作是为了了解天冬氨酸蛋白酶跨度的作用。 取自紫海胆，(1)正常 发展和(Ii)在其他发育阶段调节BMP信号 系统。 I)虽然SPAN基因表达的模式和调控 广泛研究，发育表达和生化 Span蛋白水解酶的活性尚未确定。我有过 研制了一种抗SPAN的多克隆抗血清 蛋白水解酶在发育中的囊胚顶端的表达。 为了了解SPAN在形态发生中的作用，我们提出了一些方法 干扰体内SPAN活性并分离可能的生化物质 目标(S)。 Ii)相关的ASTIN蛋白水解酶。包括一个Tolloid大家族 脊椎动物和果蝇的分子在 形成模式，并被认为是通过增强BMP信号起作用。我们 为该途径中的SPAN活性提供了生化解释 BMP拮抗剂Chordin在体外实验中被Span切割。在……里面 除了它们在早期发育中的作用外，BMP还具有很强的成骨作用。 探员们。我们将直接测试SPAN调节骨骼生长的能力 在大鼠下颌骨缺损模型中。 关键词：虾青素蛋白，转化生长因子-β-骨形态发生蛋白 信号、细胞外基质、海胆

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