Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs.
Evidence for the direct involvement of transmembrane region 6 of the lutropin/choriogonadotropin receptor in activating Gs.
复制标题
促黄体激素/绒毛膜促性腺激素受体跨膜区 6 直接参与 Gs 激活的证据。
DOI：
10.1074/jbc.272.23.14586
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Segaloff,DL
中科院分区：
文献类型：
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作者：
Abell,AN;Segaloff,DL
促黄体生成素/绒毛膜促性腺激素受体(LHR)是一种七螺旋受体，主要与Gs相互作用。以前的研究表明，某些形式的家族性男性性早熟与人类LHR第六跨膜区的突变有关，该突变导致该受体的结构性激活。这项研究表明，与LHR第六跨膜区下部相对应的多肽可以显著激活腺酰环化酶的活性。用野生型VS Cyc−S49细胞的膜进行的实验表明，该肽对循环酶的刺激是由于Gs的激活。因此，我们的数据证明了大鼠LHR跨膜区6在激活G方面的直接作用，从而增加了LHR跨膜区6的突变可能直接影响受体与Gs的偶联的可能性。值得注意的是，这些数据首次证明了在细胞内环区没有任何贡献的情况下，G蛋白偶联受体的跨膜部分激活G蛋白的能力。
The luteinizing hormone/chorionic gonadotropin receptor (LHR) is a heptahelical receptor that interacts primarily with Gs. Previous studies by others have shown that some forms of familial male precocious puberty are associated with mutations of the human LHR in the sixth transmembrane region that result in constitutive activation of the receptor. This study demonstrates that a peptide corresponding to the lower portion of the sixth transmembrane region of the LHR can significantly activate adenylyl cyclase activity. Experiments with membranes derived from wild-typeversus cyc−S49 cells demonstrate that the stimulation of cyclase by this peptide is due to an activation of Gs. As such, our data demonstrate a direct role for transmembrane region 6 of the rat LHR in activating Gsand therefore raise the possibility that mutations in transmembrane region 6 of the LHR may directly affect the coupling of the receptor to Gs. Significantly, these data are the first to demonstrate the ability of a transmembrane portion of a G protein-coupled receptor, in the absence of any contributions from an intracellular loop region, to activate a G protein.