Sustained cyclic AMP production by parathyroid hormone receptor endocytosis.
Sustained cyclic AMP production by parathyroid hormone receptor endocytosis.
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DOI：
10.1038/nchembio.206
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发表时间：
2009-10
影响因子：
14.8
通讯作者：
Vilardaga, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Ferrandon, Sebastien;Feinstein, Timothy N.;Castro, Marian;Wang, Bin;Bouley, Richard;Potts, John T.;Gardella, Thomas J.;Vilardaga, Jean-Pierre
由G蛋白偶联的甲状旁腺激素受体1型(PTHR)介导的细胞信号转导是骨和肾脏生理的基础。目前还不清楚这两个配体系统--PTH(内分泌和稳态)和PTH相关肽(PTHrP)--如何在只有一个受体的情况下有效地工作，并触发不同持续时间的cAMP反应。在这里，我们通过测量PTHR信号级联中每个反应步骤的激活和失活动力学来分析配体的反应。我们发现，在G蛋白偶联和cAMP产生的时间框架内，PTHrP1-36的作用仅限于细胞表面，而PTH1-34已经移动到内化的隔室，在那里它仍然与PTHR和GαS联系在一起，可能是一个持久的、活性的三元复合体。这些显著的差异提示了PTH和PTHrP诱导不同反应的机制，这些结果表明cAMP产生仅起源于细胞膜的中心信条必须修改。
Cell signaling mediated by the G protein-coupled parathyroid hormone receptor type 1 (PTHR) is fundamental to bone and kidney physiology. It has been unclear how the two ligand systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—can effectively operate with only one receptor and trigger different durations of the cAMP responses. Here we analyze the ligand response by measuring the kinetics of activation and deactivation for each individual reaction step along the PTHR signaling cascade. We found that during the time frame of G protein coupling and cAMP production, PTHrP1–36 action was restricted to the cell surface, whereas PTH1–34 had moved to internalized compartments where it remained associated with the PTHR and Gαs, potentially as a persistent and active ternary complex. Such marked differences suggest a mechanism by which PTH and PTHrP induce differential responses, and these results indicate that the central tenet that cAMP production originates exclusively at the cell membrane must be revised.
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影响因子：
46.9
作者：
Vilardaga, JP;Bünemann, M;Lohse, MJ
通讯作者：
Lohse, MJ
影响因子：
--
作者：
Dean, T;Linglart, A;Gardella, TJ
通讯作者：
Gardella, TJ
影响因子：
4.8
作者：
Berlot, CH
通讯作者：
Berlot, CH
DOI：
10.1073/pnas.0808750105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Okazaki, Makoto;Ferrandon, Sebastien;Gardella, Thomas J.
通讯作者：
Gardella, Thomas J.
影响因子：
56.9
作者：
Shenoy, SK;McDonald, PH;Lefkowitz, RJ
通讯作者：
Lefkowitz, RJ