Isoforms of the rat calcitonin receptor: consequences for ligand binding and signal transduction.
Isoforms of the rat calcitonin receptor: consequences for ligand binding and signal transduction.
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大鼠降钙素受体的亚型：配体结合和信号转导的后果。
DOI：
10.1210/endo.135.1.8013352
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发表时间：
1994
期刊：
影响因子：
4.8
通讯作者：
P. Sexton
中科院分区：
文献类型：
--
作者：
S. Houssami;D. Findlay;C. Brady;D. Myers;T. Martin;P. Sexton
两种大鼠降钙素（CT）受体亚型; C1 a和C1 b，除了在C1 b的第二胞外结构域中存在37个氨基酸的插入物外，是相同的。在这些受体在HEK-293细胞中稳定表达后，检查该插入物的功能结果。在结合竞争研究中，[125 I]鲑鱼CT（[125 I]sCT）从C1 b细胞中的解离是快速和完全的，而从C1 a细胞中的解离是缓慢和不完全的，如在其他CT受体制剂中所见。在这些研究中，C1 a受体对鲑鱼CT显示出高亲和力（Kd，0.5 +/- 1.3 nM），对猪CT的亲和力略低。人CT对[125 I]CT结合的竞争更弱。尽管配体对C1 b受体的相对亲和力得以保持，但对sCT的亲和力较低（Kd，23 +/- 2 nM），猪CT的效力比sCT低约10倍。人类和大鼠CT未能与[125 I]sCT竞争，即使在1 μ M的C1 b受体。这两种受体影响多个效应系统，表明耦合到多个G蛋白。CT肽以与结合竞争效力一致的相对功效激活腺苷酸环化酶。此外，这两种受体亚型介导的CT挑战后细胞内钙水平的快速增加。这些结果表明，大鼠CT受体的细胞外修饰导致配体识别的改变以及结合动力学的改变，但不会改变其产生多个第二信使的能力。
Two rat calcitonin (CT) receptor isoforms; C1a and C1b, are identical except for the presence of a 37-amino acid insert in the second extracellular domain of C1b. The functional consequences of this insert were examined after stable expression of these receptors into HEK-293 cells. In binding competition studies, dissociation of [125I]salmon CT ([125I]sCT) from C1b cells was rapid and complete, in contrast to dissociation from C1a cells, which was slow and incomplete, as seen with other CT receptor preparations. In these studies, C1a receptors displayed high affinity for salmon CT (Kd, 0.5 +/- 1.3 nM) and a slightly lower affinity for pig CT. Human CT competed more weakly for binding of [125I]CT. Although the relative affinities of the ligands were maintained for C1b receptors, the affinity for sCT was lower (Kd, 23 +/- 2 nM) and pig CT was approximately 10-fold less potent than sCT. Human and rat CT failed to compete with [125I]sCT even at 1 microM with the C1b receptor. Both receptors influence multiple effector systems, indicating coupling to multiple G-proteins. The CT peptides activated adenylate cyclase with relative efficacies consistent with the binding competition potencies. In addition, both receptor isoforms mediated a rapid increase in the levels of intracellular calcium after a CT challenge. These results show that an extracellular modification in the rat CT receptor results in altered ligand recognition as well as altered binding kinetics, but does not modify their ability to generate multiple second messengers.
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影响因子：
56.9
作者：
CHAKRABORTY, M;CHATTERJEE, D;BARON, R
通讯作者：
BARON, R
重组降钙素受体独立刺激 3,5-环单磷酸腺苷和 Ca2/磷酸肌醇信号通路。
DOI：
10.1210/mend.6.4.1316547
发表时间：
1992
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Chabre,O;Conklin,BR;Lin,HY;Lodish,HF;Wilson,E;Ives,HE;Catanzariti,L;Hemmings,BA;Bourne,HR
通讯作者：
Bourne,HR
影响因子：
4
作者：
TSIEN, RY;RINK, TJ;POENIE, M
通讯作者：
POENIE, M
影响因子：
56.9
作者：
JUPPNER, H;ABOUSAMRA, AB;SEGRE, GV
通讯作者：
SEGRE, GV
影响因子：
4
作者：
PUTNEY, JW
通讯作者：
PUTNEY, JW