Amino acids in the COOH-terminal region of the oxytocin receptor third intracellular domain are important for receptor function.
Amino acids in the COOH-terminal region of the oxytocin receptor third intracellular domain are important for receptor function.
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催产素受体第三胞内结构域COOH末端区域的氨基酸对于受体功能很重要。
DOI：
10.1152/ajpendo.00531.2005
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Sanborn,BarbaraM
中科院分区：
文献类型：
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作者：
Zhong,Miao;Parish,Bridgette;Murtazina,DilyaraA;Ku,Chun-Ying;Sanborn,BarbaraM
以前，在催产素（OT）受体（OTR）的第三胞内结构域（3 iC）的COOH-末端区域中的残基K6.30被鉴定为对OTR和加压素V2受体（V2 R）嵌合体V2 ROTR 3 iC中导致磷脂酶C活化的受体功能重要。在野生型V2 R中A6.28K或V6.30K的取代没有重现在V2 ROTR 3 iC中观察到的磷脂酰肌醇（PI）周转的增加。因此，K6.30的作用可能因具体情况而异。V2 ROTR 3 iC嵌合体中两个NH 2末端OTR 3 iC片段的缺失并没有减少加压素刺激的PI周转，而RVSSVKL（残基6.19-6.25）的缺失降低了受体表达。野生型OTR中该序列的缺失使表达降低50%，而不影响对[3 H]OT的亲和力。这种OTR突变体不能激活PI周转或细胞外信号调节激酶1/2磷酸化。RVSSVKL中单个残基的丙氨酸取代的影响表明OTR功能的差异重要性。R6.19A取代失去了对[3 H]OT的高亲和力位点和刺激PI周转的能力。[3 H]OT和膜表达的亲和力不受任何其他取代的影响。OTR-V6. 20 A和OTR-K6. 24 A突变体的功能与野生型OTR一样，而OTR S6.21A、S6.22A和V6.23A突变体显示出激活PI周转的能力受损（OTR的20-40%），OTR-L 6. 25 A突变体显示出组成型活性。总之，OTR第三胞内结构域的COOH末端区域中RVSSVKL片段中的特定氨基酸影响OTR激活G蛋白介导的作用的能力。
Previously, residue K6.30 in the COOH-terminal region of the third intracellular domain (3iC) of the oxytocin (OT) receptor (OTR) was identified as important for receptor function leading to phospholipase C activation in both OTR and the vasopressin V2receptor (V2R) chimera V2ROTR3iC. Substitution of either A6.28K or V6.30K in wild-type V2R did not recapitulate the increase in phosphatidylinositide (PI) turnover observed in V2ROTR3iC. Hence, the role of K6.30 may be context-specific. Deletion of two NH2-terminal OTR3iC segments in the V2ROTR3iC chimera did not diminish vasopressin-stimulated PI turnover, whereas deletion of RVSSVKL (residues 6.19–6.25) reduced receptor expression. Deletion of this sequence in wild-type OTR reduced expression by 50% without affecting affinity for [3H]OT. This OTR mutant was unable to activate PI turnover or extracellular signal-regulated kinase 1/2 phosphorylation. The effects of alanine substitution for individual residues in RVSSVKL indicated differential importance for OTR function. The R6.19A substitution lost high-affinity sites for [3H]OT and the ability to stimulate PI turnover. Affinity for [3H]OT and membrane expression was not affected by any other substitutions. OTR-V6.20A and OTR-K6.24A mutants functioned as well as wild-type OTR, whereas OTR S6.21A, S6.22A, and V6.23A mutants exhibited impaired abilities to activate PI turnover (20–40% of OTR), and the OTR-L6.25A mutant exhibited constitutive activity. In conclusion, specific amino acids in the RVSSVKL segment in the COOH-terminal region of the third intracellular domain of OTR influence the ability of OTR to activate G protein-mediated actions.