NEW THROMBOREGULATORY PROTEIN, ANNEXIN II

新的血栓调节蛋白，Annexin II

• 批准号: 6536950
• 负责人: KATHERINE AMBERSON HAJJAR
• 金额: $ 39.71万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536950
• 关键词: DNA footprinting; PC12 cells; angiogenesis; annexins; cardiovascular system; cell differentiation; chick embryo; developmental genetics; embryo /fetus; gel mobility shift assay; gene expression; genetic promoter element; hepatocyte growth factor; histogenesis; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; matrigel; messenger RNA; neurogenesis; neurotrophic factors; plasmin; protein structure function; vertebrate embryology

The overall goal of the current application is to understand the mechanisms by which expression of annexin II may be controlled in specific settings of cellular differentiation and development. Our published studies have revealed a role for annexin II in promoting assembly of plasminogen and tissue plasminogen activator, and subsequent plasmin generation on the surface of endothelial cells, macrophages, and myeloid cells. New preliminary data suggest that the expression of annexin II may be developmentally regulated in both the chick an" mouse embryo. While annexin II is expressed in the developing brain and spinal cord, this expression is lost in the adult organism. Similarly, expression of annexin II is strongly upregulated in neuronal cells in vitro by the neurotrophin, nerve growth factor (NGF). At the same time, annexin II is expressed in the embryonic heart, but not in the postnatal heart. Similarly, expression of annexin II in endothelial cells is upregulated by the angiogenic factor, hepatocyte growth factor. These new findings suggest that the function of annexin II may extend beyond the maintenance of blood fluidity. We hypothesize that annexin II promotes normal neuronal an" cardiovascular differentiation in the developing vertebrate embryo by fostering cell surface proteolytic activity an" promoting tissue remodeling. To investigate this hypothesis, we plan [1] to determine the pattern of annexin II expression an" the consequences of its disruption during organogenesis in the developing chick embryo, [2] to identify the temporal an" spatial settings in which the annexin II promoter is active during development, [3] to delineate the mechanism by which NGF stimulates annexin II protein an" mRNA expression, and [4] to define the role of annexin II in blood vessel development in response to angiogenic growth factors.

当前应用的总体目标是了解可以在细胞分化和发育的特定环境中控制膜联蛋白II的表达的机制。我们发表的研究揭示了膜联蛋白II在促进纤溶酶原和组织纤溶酶原激活剂的组装中的作用，以及随后在内皮细胞，巨噬细胞和髓样细胞表面产生纤溶酶素的作用。新的初步数据表明，膜联蛋白II的表达在雏鸡和“小鼠胚胎”中都可能受到调节。虽然膜联蛋白II在发育中的大脑和脊髓中表达，但这种表达在成年有机体中丧失。类似地，同样，膜联蛋白II的表达在神经蛋白的表达中在神经蛋白的表达中强烈上调，在神经素中，神经蛋白II IS nise nise nise nise nise nise nise nrvery ndgf inve ngff inve ngf inve ngf inve ngf ngf inve ngf inve。胚胎的心脏，但在产后的心脏中，内皮细胞中膜联蛋白II的表达是由肝细胞生长因子上调的。 proteolytic activity an" promoting tissue remodeling. To investigate this hypothesis, we plan [1] to determine the pattern of annexin II expression an" the consequences of its disruption during organogenesis in the developing chick embryo, [2] to identify the temporal an" spatial settings in which the annexin II promoter is active during development, [3] to delineate the mechanism by which NGF stimulates annexin II protein an" mRNA表达和[4]来定义膜联蛋白II在血管发育中的作用，以响应血管生长因子。