TYROSINE PHOSPHATASES IN ENDOTHELIAL GROWTH CONTROL

酪氨酸磷酸酶在内皮生长控制中的作用

• 批准号: 2728977
• 负责人: TOM DANIEL
• 金额: $ 4.86万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2728977
• 关键词: TYROSINE; PHOSPHATASES; ENDOTHELIAL; GROWTH; CONTROL

DESCRIPTION (Adapted from Investigator's Abstract): Repair and maintenance of vascular integrity requires that endothelial cells display an integrated, coordinated regulation of cell-cell and cell- matrix attachment to minimize extravasation of blood during wound healing, tumor growth and in the dynamic expansion and contraction of microvascular beds during postnatal angiogenesis. Possible roles of tyrosine phosphatases in modulating endothelial responses to proliferative stimuli have been suggested by effects of the protein tyrosine phosphatase inhibitor, orthovanadate, to promote proliferation of cultured endothelial cells. A receptor tyrosine phosphatase they have cloned from human renal microvascular endothelial cells, DEP-1, regulates endothelial responses to stimuli for proliferation, migration, and capillary morphogenesis. They will explore molecularly specific roles for DEP-1 by assessing effects that loss of DEP-1 function and gain of function have on behavior of microvascular and large vessel endothelial cells; those responses will be compared with responses in non-endothelial cell types. Emphasis will be placed on defining effects DEP-1 mediates on the density- and matrix-dependent growth and differentiation of cultured endothelial cells. Mechanisms mediating DEP-1 accumulation will be explored, and substrates with which it interacts will be identified. Roles for intracellular targeting of the catalytically active cytoplasmic tyrosine phosphatase domain in biological function will be determined. These studies promise to define mechanisms that modulate endothelial responses to proliferative stimuli in vascularized tumors, diabetes and atherosclerosis and to assign function to tyrosine phosphatases that have not been previously defined in endothelial systems.

描述（改编自研究者摘要）：修复和 维持血管完整性需要内皮细胞 显示细胞间和细胞间的整合、协调调节 基质附着可最大程度地减少伤口期间血液外渗 愈合、肿瘤生长以及动态扩张和收缩 产后血管生成期间的微血管床。可能的角色 酪氨酸磷酸酶调节内皮反应 蛋白质的作用表明增殖刺激 酪氨酸磷酸酶抑制剂，原钒酸盐，促进增殖 培养的内皮细胞。他们有酪氨酸磷酸酶受体 从人肾微血管内皮细胞克隆，DEP-1， 调节内皮细胞对增殖刺激的反应， 迁移和毛细血管形态发生。 他们将通过评估来探索 DEP-1 的分子特异性作用 DEP-1 功能丧失和功能获得的影响 微血管和大血管内皮细胞的行为；那些 将反应与非内皮细胞类型的反应进行比较。 重点将放在定义 DEP-1 对 培养物的密度和基质依赖性生长和分化 内皮细胞。介导 DEP-1 积累的机制将是 进行探索，并确定与其相互作用的底物。 催化活性细胞内靶向的作用 细胞质酪氨酸磷酸酶结构域的生物学功能是 决定。这些研究有望定义调节机制 血管化肿瘤中内皮细胞对增殖刺激的反应， 糖尿病和动脉粥样硬化并将功能分配给酪氨酸 以前尚未在内皮细胞中定义的磷酸酶 系统。