Kosugi S, Mori T
Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.
FEBS Lett. 1994 Mar 21;341(2-3):162-6. doi: 10.1016/0014-5793(94)80449-4.
We investigated the role of the 1st cytoplasmic loop of the thyrotropin receptor (TSHR) on signal transduction using mutants as we did the 2nd and 3rd cytoplasmic loops [Kosugi S. et al. (1994) Mol. Endocrinol., in press; and 7, 1009-1020]. Five substitution mutants involving the first cytoplasmic loop showed a TSH- or Graves' IgG-stimulated cAMP response despite the low TSH binding Bmax. All the mutants completely lost or markedly decreased the TSH- or Graves' IgG-stimulated inositol phosphate increase. These findings suggest that the 1st cytoplasmic loop of the TSHR does not play a crucial role in agonist-induced adenylate cyclase activation but that it is important for phosphoinositide signaling.
我们使用突变体研究促甲状腺激素受体(TSHR)的第一个胞质环在信号转导中的作用,就像我们对第二个和第三个胞质环所做的那样[小杉S.等人(1994年),《分子内分泌学》,即将发表;以及第7卷,1009 - 1020页]。涉及第一个胞质环的五个替代突变体尽管促甲状腺激素结合Bmax较低,但仍显示出促甲状腺激素或格雷夫斯病免疫球蛋白刺激的环磷酸腺苷反应。所有突变体完全丧失或显著降低了促甲状腺激素或格雷夫斯病免疫球蛋白刺激的肌醇磷酸增加。这些发现表明,TSHR的第一个胞质环在激动剂诱导的腺苷酸环化酶激活中不发挥关键作用,但对磷酸肌醇信号传导很重要。