Molecular cloning and characterization of avian bombesin-like peptide receptors: new tools for investigating molecular basis for ligand selectivity
Molecular cloning and characterization of avian bombesin-like peptide receptors: new tools for investigating molecular basis for ligand selectivity
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DOI：
10.1038/sj.bjp.0705282
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发表时间：
2003-06-01
影响因子：
7.3
通讯作者：
Ohki-Hamazaki, H
中科院分区：
文献类型：
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作者：
Iwabuchi, M;Ui-Tei, K;Ohki-Hamazaki, H
1 Bombesin （BN）最初从两栖动物中分离出来，在结构上与哺乳动物中发现的BN样肽家族相关，其中包括胃泌素释放肽（GRP）和神经素B （NMB）。这些肽对分泌、平滑肌收缩、代谢和行为有重要影响。2鸡GRP- r （chGRP-R）的氨基酸序列与哺乳动物和两栖动物的GRP- r高度一致，该受体对GRP、BN和合成bombesin激动剂[D-Phe(6)、β - ala（11）、Phe（13）、Nle(14)] bombesin(6 - 14) （[FAFNl] BN(6 - 14)）具有高亲和力。chGRP-R基因定位于鸡染色体1q23远端-q24近端，而鸡与其他人类x连锁基因的同源性也已被定位ChBRS-3.5与哺乳动物炸弹蛋白样肽受体亚型-3和两栖动物炸弹蛋白样肽受体亚型-4序列相似，对[fafn1] BN具有高亲和力（6 - 14），对BN具有中等亲和力，但对GRP和nmb具有低亲和力。4两种受体均在脑组织中表达，而仅在胃肠道组织中表达当在仓鼠卵巢K1细胞中表达时，这些受体在激动剂刺激下介导细胞内钙动员。这些结果表明，鸟类中可能存在一种新的BN肽作为chBRS-3.5.6的内源性配体。我们讨论了负责配体选择性的受体序列，这些关于鸟类BN样肽受体的知识将有助于我们了解BN样肽受体激动剂敏感性的分子基础。
1 Bombesin (BN), originally isolated from amphibians, is structurally related to a family of BN-like peptides found in mammals, which include gastrin-releasing peptide (GRP) and neuromedin B (NMB). These peptides have important effects on secretion, smooth muscle contraction, metabolism and behavior. Here we report cloning and characterization of two subtypes of BN-like peptide receptors in Aves.2 The amino-acid sequence of chick GRP-R (chGRP-R) is highly identical with mammalian and amphibian GRP-R, and this receptor showed high affinity for GRP, BN and synthetic bombesin agonist, [D-Phe(6), beta-Ala(11), Phe(13), Nle(14)] bombesin(6 - 14) ([ FAFNl] BN( 6 - 14)). The chGRP-R gene was localized to chicken chromosome 1q23distal-q24proximal, where chick homologs of other human X-linked genes have also been mapped.3 ChBRS-3.5, having sequence similarities to both mammalian bombesin-like peptide receptor subtype-3 and amphibian bombesin-like peptide receptor subtype-4, showed high affinity for [ FAFNl] BN( 6 - 14), moderate affinity for BN, but low affinity for both GRP and NMB.4 Expression of both receptors was detected in brain, but only chGRP-R was expressed in gastrointestinal (GI) tissues.5 When expressed in Chinese hamster ovary K1 cells, these receptors mediate intracellular calcium mobilization upon agonist stimulation. These results suggest that a novel BN peptide may occur in Aves as an endogenous ligand for chBRS-3.5.6 The receptor sequences responsible for ligand selectivities were discussed and this knowledge about avian BN-like peptide receptors will help us to understand the molecular basis for agonist sensitivities of BN-like peptide receptors.