In summary, we identified and characterized a novel G αq/11 agonist molecule acting at the TSHR and which showed a marked anti-proliferative ability. Hence, Gq biased activation of the TSHR is capable of ameliorating the proliferative signals from its orthosteric ligand and may offer a therapeutic option for thyroid growth modulation.

2017年7月24日 · The TSHR activates different G-protein subtypes and signaling pathways, of which Gs and Gq induced signaling are of highest importance in the thyroid gland. A proper interplay between TSH and TSHR is pivotal for thyroid growth and regulated production and release of thyroid hormones (TH).

2020年6月26日 · By virtue of its structural property, the TSH receptor (TSHR) has a unique ability to engage different G proteins making it highly amenable to selective signaling. In this study, we describe the identification and characterization of a novel small molecule agonist to the TSHR which induces primary engagement with G αq/11 .

凭借其结构特性，tsh受体（tshr）具有与不同g蛋白结合的独特能力，使其高度适应选择性信号转导。 在这项研究中，我们描述了TSHR的新型小分子激动剂的鉴定和表征，该激动剂可诱导与Gαq/ 11的主要结合。

2022年4月13日 · Within the ICL2 of the TSHR, amino acids Met527, Arg528, and Asp530 appeared to be critical for both Gs and Gq activation, whereas alanine mutations of Ile523, Phe525, and Leu529 selectively impaired Gq-mediated signaling.

2022年8月8日 · Comparisons of the active and inactivated structures of TSHR with those of the luteinizing hormone/choriogonadotropin receptor (LHCGR) reveal a universal activation mechanism of glycoprotein ...

Genetic analysis showed that he was compound heterozygous for two known missense mutations (Arg109Gln and Arg450His) in the TSHR gene. Further, the signal transduction of Arg109Gln-TSHR was defective in both Gs- and Gq-coupled pathways, while Arg450His-TSHR showed Gq-dominant defect.

2010年3月18日 · In this study we wanted to gain insights into selectivity mechanisms between G-protein-coupled receptors (GPCR) and different subtypes of G-proteins. The thyrotropin receptor (TSHR) binds G-proteins promiscuously and activates both Gs (cAMP) and Gq (IP).

2020年6月1日 · In summary, we identified and characterized a novel Gαq/11 agonist molecule acting at the TSHR and which showed a marked anti-proliferative ability. Hence, Gq biased activation of the TSHR is...

2022年9月27日 · tsh-tshr结构与cg-lhcgr（绒毛膜促性腺激素受体）复合物的活性结构高度相似，表明tsh和cg都通过共同机制稳定受体活性构象。有趣的是，tshr ecd相对于lhcgr结构额外旋转了约12°到直立位置。 图3. tsh和tshr之间的激素特异性和相互作用