INTERNALIZATION OF PARATHYROID HORMONE RECEPTOR

甲状旁腺激素受体的内化

• 批准号: 6140446
• 负责人: HESHAM A TAWFEEK
• 金额: $ 4.63万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6140446
• 关键词: adenylate cyclase; biological signal transduction; calcium flux; cell line; green fluorescent proteins; hormone receptor; mitogen activated protein kinase; parathyroid hormone related protein; parathyroid hormones; phospholipase C; phosphorylation; receptor binding; receptor expression; receptor sensitivity

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.

甲状旁腺激素 (PTH) 和甲状旁腺激素相关肽 (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受体的内化可能导致PTH和PTHrP反应的脱敏和/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) 内化需要激活 PTH/PTHrP 受体，2) PTH 诱导的磷酸化是内化所需的，3) 内化可能通过腺苷酸环化酶、磷脂酶 C、钙和/或 MAP 激酶在 PTH/PTHrP 受体信号传导中发挥重要作用。