TYROSINE PHOSPHATASES IN ENDOTHELIAL GROWTH CONTROL

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 显示出细胞-细胞和细胞- 基质附着以最小化伤口期间的血液外渗 愈合，肿瘤生长和动态扩张和收缩 微血管床在出生后的血管生成。可能作用 酪氨酸磷酸酶在调节内皮细胞对 蛋白质的作用已经表明了增殖刺激 酪氨酸磷酸酶抑制剂，原钒酸盐，促进增殖 培养的内皮细胞。一种受体酪氨酸磷酸酶， 克隆自人肾微血管内皮细胞，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的分子特异性作用， DEP-1功能的丧失和功能的获得对 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中的反应进行比较。 重点将放在定义DEP-1介导的对 密度和基质依赖性生长和分化培养的 内皮细胞介导DEP-1积累的机制将是 探索，并将确定与其相互作用的底物。 细胞内靶向的催化活性 胞质酪氨酸磷酸酶结构域在生物学功能中将是 测定这些研究有望确定调节 血管化肿瘤中内皮对增殖刺激的反应， 糖尿病和动脉粥样硬化，并分配功能酪氨酸 以前在内皮细胞中没有定义的磷酸酶 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.