FUNCTION OF EXTRACELLULAR MATRIX PROTEIN FIBULIN 2

描述(改编自申请人的摘要)：长期目标 这一应用是为了了解纤维蛋白-2的生物学功能，一种 最近发现了细胞外基质蛋白。纤维蛋白-2属于一种 生长中的含有串联的细胞外基质蛋白超家族 钙结合的EGF样重复序列阵列。它既可以在 许多器官的基底膜和间质结缔组织， 包括心脏、皮肤、骨骼肌、角膜、肾脏和血液 船只。体外结合分析表明，纤毛蛋白-2与 纤维连接蛋白、Nidogen/entactin、纤维蛋白-1和其他几种细胞外 基质配体。此外，纤维蛋白-2与纤维蛋白-1在 某些组织的微纤维。这些观察结果表明，纤维蛋白-2可以 被结合到不同类型的细胞外基质中，并可能发挥作用 在不同的生物过程中发挥关键作用。为了澄清这个问题 关于纤毛蛋白-2的生物学功能，提出了以下具体目标： (1)研究纤维蛋白-2的生物合成、加工和组装。 培养细胞；(2)研究纤溶蛋白-2的结构和功能。 重组纤维蛋白-2片段用于识别负责结合的结构域 纤维连接蛋白、尼多芬、纤维蛋白-1和基质组装；(3)制备 带有fiblin-2基因的转基因小鼠被灭活或突变，以便 调查突变的后果；以及(4)表征 小鼠纤毛蛋白-2基因启动子区域及鉴定元件 控制基因表达。

DESCRIPTION (Adapted from the Applicant's Abstract): The long-term goal of this application is to understand the biological function of Fibulin-2, a recently identified extracellular matrix protein. Fibulin-2 belongs to a growing super-family of extracellular matrix proteins that contain tandem arrays of calcium-binding EGF-like repeats. It is found both in the basement membranes, and interstitial connective tissues of many organs, including the heart, skin, skeletal muscle, cornea, kidney and blood vessels. In vitro binding assays show that fibulin-2 interacts with fibronectin, nidogen/entactin, fibrillin-1, and several other extracellular matrix ligands. In addition, fibulin-2 colocalizes with fibrillin-1 in microfibrils of some tissues. These observations suggest that fibulin-2 can be incorporated into different types of extracellular matrices and may play critical roles in diverse biological processes. In order to elucidate the biological function of fibulin-2, the following Specific Aims are proposed: (1) to study the biosynthesis, processing and assembly of fibulin-2 in cultured cells; (2) to study the structure/function of fibulin-2, by using recombinant fibulin-2 fragments to identify domains responsible for binding fibronectin, nidogen, fibrillin-1, and for matrix assembly; (3) to prepare transgenic mice with the fibulin-2 gene inactivated, or mutated, in order to investigate the consequences of the mutations; and (4) to characterize the promoter region of the mouse fibulin-2 gene and identify elements controlling the gene expression.