INTERNALIZATION OF PARATHYROID HORMONE RECEPTOR

甲状旁腺激素（PTH）和甲状旁腺相关肽（PTHrP）的生物学作用是通过共同的PTH/PTHrP受体介导的。 PTH/PTHrP受体的下调和脱敏是PTH/PTHrP受体生理学中的重要过程。 PTH或PTHrP与其受体的结合导致受体磷酸化、内化、脱敏、再循环和/或降解。 PTH/PTHrP受体的内化可导致PTH和PTHrP应答的脱敏和/或再敏化和/或受体的下调和降解。 在这个项目中，我将使用稳定表达绿色荧光蛋白（GFP）标记的PTH/PTHrP受体的细胞系来检验以下假设：1）PTH/PTHrP受体的激活是内化所必需的，2）PTH诱导的磷酸化是内化所必需的，3）内化可能在PTH/PTHrP受体通过腺苷酸环化酶，磷脂酶C，钙和/或MAP激酶。

The biologic actions of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are mediated through a common PTH/PTHrP receptor. Down-regulation and desensitization of the PTH/PTHrP receptor is an important process in PTH/PTHrP receptor physiology. Binding of PTH or PTHrP to its receptor results in receptor phosphorylation, internalization, desensitization, recycling and or degradation. Internalization of the PTH/PTHrP receptor may lead to desensitization and/or re-sensitization of the PTH and PTHrP responses and/or downregulation and degradation of the receptor. In this project I will use cell lines, stably expressing a green fluorescent protein (GFP) tagged PTH/PTHrP receptor, to examine the hypotheses that 1) activation of the PTH/PTHrP receptor is required for internalization, 2) PTH-induced phosphorylation is required for internalization and 3) that internalization may have an important role in PTH/PTHrP receptor signaling through adenylate cyclase, phospholipase C, calcium and/or MAP kinase.