TYROSINE PHOSPHATASES IN ENDOTHELIAL GROWTH CONTROL

描述(改编自调查人员摘要)：修复和 维持血管完整性需要内皮细胞 显示细胞-细胞和细胞-的集成、协调调节 基质附着可最大限度地减少伤口的血液外溢 愈合、肿瘤生长和肿瘤的动态扩张和收缩 出生后血管生成过程中的微血管床。可能扮演的角色 酪氨酸磷酸酶在调节血管内皮细胞对 蛋白质的作用提示有增殖刺激作用。 酪氨酸磷酸酶抑制剂，原钒酸，促进增殖 培养的内皮细胞。他们有一种受体酪氨酸磷酸酶 从人肾微血管内皮细胞克隆的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DEP-1在分子上的特定作用 DEP-1功能丧失和功能获得对机体功能的影响 微血管和大血管内皮细胞的行为 反应将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 依赖密度和基质的培养细胞的生长和分化 内皮细胞。调节DEP-1积聚的机制将是 探索，并将确定与其相互作用的底物。 细胞内靶向催化活性物质的作用 胞质酪氨酸磷酸酶结构域的生物学功能 下定决心。这些研究承诺定义调控机制 血管化肿瘤内皮细胞对增殖刺激的反应 糖尿病与动脉粥样硬化及酪氨酸的功能分配 以前未在内皮细胞中定义的磷酸酶 系统。

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.