FUNCTION OF EXTRACELLULAR MATRIX PROTEIN FIBULIN 2

描述（改编自申请人的摘要）： 本申请旨在了解Fibulin-2的生物学功能， 最近发现的细胞外基质蛋白。 Fibulin-2属于A 生长的细胞外基质蛋白超家族， 钙结合EGF样重复序列阵列。 它既存在于 基底膜和许多器官的间质结缔组织， 包括心脏、皮肤、骨骼肌、角膜、肾脏和血液 船舶. 体外结合试验表明，fibulin-2与 纤连蛋白、巢蛋白/巢蛋白、纤连蛋白-1和其他几种细胞外 基质配体 此外，fibulin-2与p53蛋白-1共定位， 某些组织的微纤维。 这些观察结果表明，fibulin-2可以 可以被整合到不同类型的细胞外基质中， 在不同的生物过程中起着关键作用。 为了阐明本 关于fibulin-2的生物学功能，提出了以下具体目的： (1)研究fibulin-2的生物合成、加工和组装， （2）研究fibulin-2的结构和功能， 重组纤蛋白-2片段以鉴定负责结合的结构域 纤连蛋白、巢蛋白、纤连蛋白-1和用于基质组装;（3）制备 用fibulin-2基因失活或突变的转基因小鼠， 研究突变的后果;（4）表征突变的 小鼠fibulin-2基因启动子区及其识别元件 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.