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促甲状腺激素(TSH)和促黄体生成素/绒毛膜促性腺激素(LH/CG)受体的细胞外结构域嵌合体显示,中间区域(氨基酸171 - 260)在高亲和力TSH结合中起关键作用。

Extracellular domain chimeras of the TSH and LH/CG receptors reveal the mid-region (amino acids 171-260) to play a vital role in high affinity TSH binding.

作者信息

Nagayama Y, Russo D, Chazenbalk G D, Wadsworth H L, Rapoport B

机构信息

Thyroid Molecular Biology Unit, V.A. Medical Center, San Francisco, California 94121.

出版信息

Biochem Biophys Res Commun. 1990 Dec 31;173(3):1150-6. doi: 10.1016/s0006-291x(05)80906-4.

DOI:10.1016/s0006-291x(05)80906-4
PMID:2176485
Abstract

We constructed a series of TSH-LH/CG receptor chimeras by homologous substitution of relatively small regions of the TSH receptor extracellular domain for the corresponding region of the extracellular domain of the LH/CG receptor. Constructs were stably expressed in Chinese hamster ovary cells. Of the five chimeric receptors, only TSH-LHR-14, which contains mid-region domain C (amino acid residues 171-260) of the extracellular component of the TSH receptor, exhibited TSH binding of relatively high affinity. Consistent with this TSH binding, chimera TSH-LHR-14 was the only one that demonstrated a functional response to TSH stimulation in terms of intracellular cAMP generation. These data indicate that domain C plays a vital role in TSH receptor function.

摘要

我们通过将促甲状腺激素(TSH)受体细胞外结构域的相对小区域与促黄体生成素/绒毛膜促性腺激素(LH/CG)受体细胞外结构域的相应区域进行同源替换,构建了一系列TSH-LH/CG受体嵌合体。构建体在中国仓鼠卵巢细胞中稳定表达。在五个嵌合受体中,只有包含TSH受体细胞外成分中间区域结构域C(氨基酸残基171 - 260)的TSH-LHR-14表现出相对高亲和力的TSH结合。与这种TSH结合一致,嵌合体TSH-LHR-14是唯一一个在细胞内cAMP生成方面对TSH刺激表现出功能性反应的。这些数据表明结构域C在TSH受体功能中起至关重要的作用。

相似文献

1
Extracellular domain chimeras of the TSH and LH/CG receptors reveal the mid-region (amino acids 171-260) to play a vital role in high affinity TSH binding.促甲状腺激素(TSH)和促黄体生成素/绒毛膜促性腺激素(LH/CG)受体的细胞外结构域嵌合体显示,中间区域(氨基酸171 - 260)在高亲和力TSH结合中起关键作用。
Biochem Biophys Res Commun. 1990 Dec 31;173(3):1150-6. doi: 10.1016/s0006-291x(05)80906-4.
2
Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function.促甲状腺激素-促黄体生成素/绒毛膜促性腺激素受体胞外域嵌合体作为促甲状腺激素受体功能的探针
Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):902-5. doi: 10.1073/pnas.88.3.902.
3
Eleven amino acids (Lys-201 to Lys-211) and 9 amino acids (Gly-222 to Leu-230) in the human thyrotropin receptor are involved in ligand binding.人促甲状腺激素受体中的11个氨基酸(赖氨酸-201至赖氨酸-211)和9个氨基酸(甘氨酸-222至亮氨酸-230)参与配体结合。
J Biol Chem. 1991 Aug 15;266(23):14926-30.
4
Thyrotropin stimulation of the lutropin/choriogonadotropin receptor: different sites mediate agonist activity and high affinity binding.促甲状腺激素对促黄体生成素/绒毛膜促性腺激素受体的刺激作用:不同位点介导激动剂活性和高亲和力结合。
Thyroid. 1994 Winter;4(4):447-57. doi: 10.1089/thy.1994.4.447.
5
Chimeric studies of the extracellular domain of the rat thyrotropin (TSH) receptor: amino acids (268-304) in the TSH receptor are involved in ligand high affinity binding, but not in TSH receptor-specific signal transduction.大鼠促甲状腺激素(TSH)受体细胞外结构域的嵌合研究:TSH受体中的氨基酸(268 - 304)参与配体的高亲和力结合,但不参与TSH受体特异性信号转导。
Endocr J. 1993 Jun;40(3):363-72. doi: 10.1507/endocrj.40.363.
6
Further studies of amino acids (268-304) in thyrotropin (TSH)--lutropin/chorionic gonadotropin (LH/CG) receptor chimeras: cysteine-301 is important in TSH binding and receptor tertiary structure.促甲状腺激素(TSH)-促黄体生成素/绒毛膜促性腺激素(LH/CG)受体嵌合体中氨基酸(268-304)的进一步研究:半胱氨酸-301在TSH结合和受体三级结构中起重要作用。
Thyroid. 1994 Spring;4(1):43-8. doi: 10.1089/thy.1994.4.43.
7
High affinity binding of thyrotropin (TSH) and thyroid-stimulating autoantibody for the TSH receptor extracellular domain.促甲状腺激素(TSH)与甲状腺刺激自身抗体对TSH受体细胞外结构域的高亲和力结合。
Thyroid. 1994 Summer;4(2):155-9. doi: 10.1089/thy.1994.4.155.
8
Thyroid stimulatory autoantibodies in different patients with autoimmune thyroid disease do not all recognize the same components of the human thyrotropin receptor: selective role of receptor amino acids Ser25-Glu30.不同自身免疫性甲状腺疾病患者体内的甲状腺刺激自身抗体并非都识别促甲状腺激素受体的相同成分:受体氨基酸Ser25 - Glu30的选择性作用
J Clin Endocrinol Metab. 1992 Dec;75(6):1425-30. doi: 10.1210/jcem.75.6.1361193.
9
Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.用嵌合促甲状腺素-促黄体生成素/绒毛膜促性腺激素受体测定刺激性和抑制性促甲状腺素(TSH)受体自身抗体的结合域
J Clin Invest. 1991 Jul;88(1):336-40. doi: 10.1172/JCI115297.
10
Studies on homologous desensitization of the thyrotropin receptor in 293 human embryonal kidney cells.293人胚肾细胞促甲状腺激素受体同源脱敏的研究。
Endocrinology. 1994 Sep;135(3):1060-5. doi: 10.1210/endo.135.3.8070347.

引用本文的文献

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Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region.促黄体生成素(LH)和人绒毛膜促性腺激素(hCG)信号激活的差异由LH/CG受体的细胞外铰链区介导。
Front Endocrinol (Lausanne). 2015 Sep 22;6:140. doi: 10.3389/fendo.2015.00140. eCollection 2015.
2
Influence of the hinge region and its adjacent domains on binding and signaling patterns of the thyrotropin and follitropin receptor.铰链区及其相邻结构域对促甲状腺激素和促卵泡激素受体结合及信号传导模式的影响。
PLoS One. 2014 Oct 23;9(10):e111570. doi: 10.1371/journal.pone.0111570. eCollection 2014.
3
An attempt to induce "Graves' disease of the gonads" by immunizing mice with the luteinizing hormone receptor provides insight into breaking tolerance to self-antigens.
通过用促黄体生成素受体免疫小鼠来尝试诱导“性腺格雷夫斯病”,为打破自身抗原耐受提供了新的认识。
Thyroid. 2011 Jul;21(7):773-81. doi: 10.1089/thy.2010.0460. Epub 2011 Jun 7.
4
Defining structural and functional dimensions of the extracellular thyrotropin receptor region.定义细胞外促甲状腺激素受体区域的结构和功能维度。
J Biol Chem. 2011 Jun 24;286(25):22622-31. doi: 10.1074/jbc.M110.211193. Epub 2011 Apr 27.
5
Relationship between thyrotropin receptor hinge region proteolytic posttranslational modification and receptor physiological function.促甲状腺激素受体铰链区蛋白水解后翻译修饰与受体生理功能之间的关系。
Mol Endocrinol. 2011 Jan;25(1):184-94. doi: 10.1210/me.2010-0401. Epub 2010 Nov 24.
6
Identification of key amino acid residues in a thyrotropin receptor monoclonal antibody epitope provides insight into its inverse agonist and antagonist properties.促甲状腺激素受体单克隆抗体表位中关键氨基酸残基的鉴定有助于深入了解其反向激动剂和拮抗剂特性。
Endocrinology. 2008 Jul;149(7):3427-34. doi: 10.1210/en.2008-0207. Epub 2008 Apr 3.
7
Immunity to the thyroid-stimulating hormone receptor.对促甲状腺激素受体的免疫反应。
Springer Semin Immunopathol. 1993;14(3):309-21. doi: 10.1007/BF00195980.
8
Thyrotropin binding specificity for the thyrotropin receptor.促甲状腺激素对促甲状腺激素受体的结合特异性。
J Endocrinol Invest. 1995 Apr;18(4):283-7. doi: 10.1007/BF03347814.
9
Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors.用嵌合促甲状腺素-促黄体生成素/绒毛膜促性腺激素受体测定刺激性和抑制性促甲状腺素(TSH)受体自身抗体的结合域
J Clin Invest. 1991 Jul;88(1):336-40. doi: 10.1172/JCI115297.