Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor
Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor
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DOI：
10.1038/nm753
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发表时间：
2002-09-01
期刊：
影响因子：
82.9
通讯作者：
Varner, JA
中科院分区：
文献类型：
--
作者：
Bakre, MM;Zhu, YH;Varner, JA
血管生成是一个高度调节的过程，由天然存在的刺激剂和抑制剂的顺序作用引起。在这里，我们表明，甲状旁腺素相关肽，一种肽激素来自正常和肿瘤细胞，调节骨代谢和血管张力，是一种天然存在的血管生成抑制剂。甲状旁腺素相关肽或其N端10个氨基酸肽通过激活内皮细胞蛋白激酶A抑制体外内皮细胞迁移和体内血管生成。蛋白激酶A的活化通过抑制小GT3受体Rac来抑制细胞迁移和血管生成。相反，蛋白激酶A的抑制逆转了甲状旁腺相关肽的抗迁移和抗血管生成特性。这些研究表明，甲状旁腺相关肽是一种天然存在的血管生成抑制剂，通过激活蛋白激酶A发挥作用。
Angiogenesis is a highly regulated process that results from the sequential actions of naturally occurring stimulators and inhibitors. Here, we show that parathyroid hormone-related peptide, a peptide hormone derived from normal and tumor cells that regulates bone metabolism and vascular tone, is a naturally occurring angiogenesis inhibitor. Parathyroid hormone-related peptide or a ten-amino-acid peptide from its N terminus inhibits endothelial cell migration in vitro and angiogenesis in vivo by activating endothelial cell protein kinase A. Activation of protein kinase A inhibits cell migration and angiogenesis by inhibiting the small GTPase Rac. In contrast, inhibition of protein kinase A reverses the anti-migratory and anti-angiogenic properties of parathyroid hormone-related peptide. These studies show that parathyroid hormone-related peptide is a naturally occurring angiogenesis inhibitor that functions by activation of protein kinase A.