MAGP: A Matricellular Protein with Multiple Functions

基质相关信号事件直接影响细胞的分化、增殖和迁移，从而 影响胚胎发育、组织修复和一系列疾病，如癌症、血管疾病和肺 发展。近年来，有研究表明，一些ECM蛋白既可以发挥细胞外作用，也可以发挥细胞外作用。 在细胞内。MAGP1(微原纤维相关糖蛋白-1)就是这样一种蛋白质。除了它的胞外 作为微纤维的一个组成部分，MAGP1的另一种剪接形式可以作为稳定的细胞内 对细胞起调节作用的蛋白质。本应用程序中描述的实验将侧重于 描述MAGP1的胞内和胞外功能，特别是它们与发育和 对富含弹性蛋白的组织的调节。我们将研究MAGP在这两种弹性中起主要作用的假设 纤维组装和影响分化特异基因的表达。我们还将评估是否有可能 I使用MAGP1的独特结构域(基质结合结构域)将生物活性分子靶向 细胞外基质。我们的具体目标是：1.更好地定义MAGP作为微纤维的功能作用 蛋白质，并表征其与纤维蛋白的相互作用。2.确定MAGP1的二级和三级结构， 聚焦于基质结合域。3.了解MAGP1及其胞内交替剪接 异构体影响细胞黏附、细胞表型和组织发育。4.确定启动子的特征 MAGP1基因的序列测定及鉴定细胞中组织表达和调控的关键区域 差异化。

Matrix-associated signaling events directly influence cell differentiation, proliferation and migration, thereby impacting embryogenesis, tissue repair, and a wide range of diseases such as cancer, vascular disease, and lung development. In recent years, there has been the suggestion that some ECM proteins can act both extracellularly and intracellularly. MAGP1 (microfibril associated glycoprotein-1) is one such protein. In addition to its extracellular role as a component of microfibrils, an alternatively spliced form of MAGP1 can be found as a stable, intracellular protein that exerts a regulatory function on the cell. The experimentation described in this application will focus on Idelineating the intracellular and extracellular functions of MAGP1, particularly as they relate to development and regulation of elastin-rich tissues. We will investigate the hypothesis that MAGP plays a major role in both elastic fiber assembly and in influencing expression of differentiation-specific genes. We will also assess the possibility of Iusing a unique domain of MAGP1 (the matrix-binding domain) to target biologically active molecules to the extracellular matrix. Our specific aims are: 1. To better define the functional role of MAGP as a microfibrillar protein and characterize its interactions with fibrillin. 2. To ascertain the second & tertiary structure of MAGP1, focusing on the matrix-binding domain. 3. To understand how MAGP1 and its intracellular alternatively spliced isoforms influence cell adhesion, cell phenotypes, and tissue development. 4. To characterize the promoter sequences of the MAGP1 gene and to identify the critical regions for tissue expression and regulation during cell differentiation.