TELEOST PARATHYROID RECEPTOR BIOLOGY

最新甲状旁腺受体生物学

• 批准号: 2733932
• 负责人: DAVID Alan RUBIN
• 金额: $ 3.18万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2733932
• 关键词: biochemical evolution; hormone receptor; parathyroid hormones; protein structure function; species difference

The PTH/PTHrP receptor (PPR) mediates the biological actions of two peptide hormones, PTH and PTH-related peptide (PTHrP). PTH is the major regulator of mammalian mineral ion homeostasis. PTHrP and the common PPR are both crucial for normal development, since the disruption of either gene in mice results in lethal phenotypes with widespread abnormalities of endochondral bone formation. These "knockout" studies indicated furthermore that the common PPR is essential for mediating the functions of PTH and PTHrP, and that no other receptor can serve as a substitute. However, a novel, PTH-specific receptor (PTH2R) with significant amino acid sequence homology to the PPR was isolated from mammals, but its biological importance is not yet known. Interestingly, cDNAs encoding fish PTH2R homologs were recently isolated also from catfish and zebrafish cDNA libraries. If these novel receptors are activated only by PTH, as the mammalian PTH2R homolog, these findings suggest that a PTH-like molecule exists also in vertebrate species that do not have parathyroid glands and that PTH expression occurs in species lacking distinct parathyroid glands. In the current proposal, I will therefore study the coevolution and function of two closely related G protein-coupled PTH-/PTHrP-receptors and their two distinct ligands. The resulting findings are expected to provide evidence for possible function(s) of both ligands and both receptors in nonmammalian vertebrates, and may provide further clues for biological role(s) in mammals that are distinct from those required for the control of mineral ion homeostasis.

PTH/PTHrP受体（PPR）介导两种细胞因子的生物学作用。 肽类激素、甲状旁腺素和甲状旁腺素相关肽（PTHrP）。PTH是主要的 哺乳动物矿物质离子体内平衡的调节剂。PTHrP和共同PPR 都是正常发展的关键，因为 小鼠中的基因导致致命的表型， 软骨内骨形成这些“淘汰”研究表明， 此外，共同的PPR是必不可少的调解功能， PTH和PTHrP，没有其他受体可以作为替代品。 然而，一种新的PTH特异性受体（PTH 2 R）具有显著的氨基酸残基， 从哺乳动物中分离出与PPR同源的氨基酸序列，但其 生物学意义尚不清楚。有趣的是， PTH 2 R同源物最近也从鲶鱼和斑马鱼cDNA中分离出来 图书馆.如果这些新的受体只被PTH激活， 哺乳动物PTH 2 R同源物，这些发现表明， 也存在于没有甲状旁腺的脊椎动物物种中， PTH表达发生在缺乏明显甲状旁腺的物种中。 因此，在目前的建议中，我将研究共同进化， 两种密切相关的G蛋白偶联PTH-/PTHrP受体的功能， 两种不同的配体预计调查结果将提供 两种配体和两种受体可能功能的证据 非哺乳类脊椎动物，并可能提供进一步的线索，生物学 在哺乳动物中的作用与控制所需的作用不同 矿物质离子平衡