Weinshank R L, Adham N, Macchi M, Olsen M A, Branchek T A, Hartig P R
Neurogenetic Corporation, Paramus, New Jersey 07652.
J Biol Chem. 1991 Nov 25;266(33):22427-35.
We have cloned a novel human intronless gene encoding a G-protein-coupled receptor of the dopamine receptor family. Expression of this receptor in Cos-7 cells led to the high affinity binding of a number of dopamine D1 antagonists, with a binding profile similar to that of the previously described dopamine D1 receptor. In contrast, the agonist binding profile of this new receptor did not exactly match any previously defined dopamine D1 receptor and was notable for its unusually high affinity for dopamine. This new receptor caused a 13-fold increase in adenylylcyclase activity in transfected Cos-7 cells, following addition of dopamine. Messenger RNA encoding this new receptor appears to be widely distributed in the human brain, including cortical regions, choroid plexus, hippocampus, and brain stem. This new receptor appears to be identical to the recently described dopamine D5 receptor. A second closely related gene, GL39, was isolated and shown to represent a pseudogene, the first to be described in the G-protein-coupled receptor superfamily. This pseudogene exhibits 94% nucleotide sequence homology to the GL30 sequence and may have arisen from a gene duplication event followed by a mutation approximately 8 million years ago, prior to the emergence of man. This recently evolved pseudogene is transcribed in the human brain with a tissue distribution similar to that for its closely related functional gene.
我们克隆了一个新的人类无内含子基因，该基因编码多巴胺受体家族的一种G蛋白偶联受体。此受体在Cos-7细胞中的表达导致多种多巴胺D1拮抗剂的高亲和力结合，其结合特征与先前描述的多巴胺D1受体相似。相比之下，这种新受体的激动剂结合特征与任何先前定义的多巴胺D1受体并不完全匹配，其对多巴胺具有异常高的亲和力，这一点值得注意。在添加多巴胺后，这种新受体使转染的Cos-7细胞中的腺苷酸环化酶活性增加了13倍。编码这种新受体的信使核糖核酸似乎广泛分布于人类大脑，包括皮质区域、脉络丛、海马体和脑干。这种新受体似乎与最近描述的多巴胺D5受体相同。我们分离出了第二个密切相关的基因GL39，并证明它是一个假基因，这是G蛋白偶联受体超家族中第一个被描述的假基因。这个假基因与GL30序列具有94%的核苷酸序列同源性，可能起源于大约800万年前人类出现之前的一次基因复制事件，随后发生了突变。这个最近进化而来的假基因在人类大脑中被转录，其组织分布与其密切相关的功能基因相似。
