Molecular characterization of a second mouse pancreatic polypeptide receptor and its inactivated human homologue
Molecular characterization of a second mouse pancreatic polypeptide receptor and its inactivated human homologue
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DOI：
10.1074/jbc.271.44.27776
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发表时间：
1996-11-01
影响因子：
4.8
通讯作者：
McCaleb, ML
中科院分区：
文献类型：
--
作者：
Gregor, P;Feng, Y;McCaleb, ML
哺乳动物神经肽Y（NPY）/肽YY（PW）/胰多肽（PP）受体家族包括几种G蛋白偶联受体，即Y1、Y2和Y 4/PP 1。小鼠PP 2基因的编码区没有内含子，推测为一个由371个氨基酸组成的7个跨膜结构域（TM）受体。小鼠PP 2与小鼠Y1、小鼠Y 4/PP 1和人Y2受体的同源性分别为53、42和31。COS细胞中表达的小鼠PP 2受体与大鼠I-125-PP具有高亲和力，即IC 50 = 65 pM。I-125-PP结合的药理学表征显示PP的效力等级顺序远大于PYY大于或等于NPY，这与小鼠Y 4/PP 1受体的效力等级顺序相似。小鼠PP 2转录本在成体组织和11-，15-和17-日龄胚胎中通过北方分析未检测到。然而，在7日龄小鼠胚胎中，即在胰腺器官形成和PP产生开始之前，可检测到9.8 kb的PP 2转录物。我们还克隆了PP 2的人类同源物，PP 2是一个单拷贝基因，定位于人类染色体5 q31。令人惊讶的是，人PP 2 cDNA和基因序列在编码区显示单碱基缺失。这种移码突变预测了290个氨基酸的截短受体，而没有TM 7。用几种不同的人PP 2表达构建体转染COS-7细胞未能证实I-125-PP、I-125-PYY或I-125-NPY与细胞膜的任何特异性结合。这些数据表明，在小鼠中至少有酪氨酸PP受体，Y 4/PP 1和PP 2，而在人类中，PP 2要么是功能上无活性的，要么它已经获得了PP-独立的功能。
The family of mammalian neuropeptide Y (NPY)/peptide YY (PW)/pancreatic polypeptide (PP) receptors comprises several G protein-coupled receptors, i.e. Y1, Y2, and Y4/PP1. We now report cloning of a novel member of this family named PP2, The coding region of the mouse PP2 gene reveals no introns and predicts a seven transmembrane domain (TM) receptor of 371 amino acids, Percent identities of the mouse PP2 to mouse Y1, mouse Y4/PP1 and human Y2 receptors are 53, 42, and 31, respectively, The mouse PP2 receptor expressed in COS cells binds rat I-125-PP With high affinity, i.e. IC50 = 65 pM. Pharmacological characterization of I-125-PP binding shows a rank order of potency of PP much greater than PYY greater than or equal to NPY, which is similar to that of the mouse Y4/PP1 receptor. Mouse PP2 transcripts were not detectable by Northern analysis ill adult tissues and in 11-, 15-, and 17-day-old embryos. However, a 9.8-kb PP2 transcript was detectable in 7-day-old mouse embryo, i.e. prior to the organogenesis of pancreas and the onset of PP production. We have also cloned the human homologue of PP2, which is a single copy gene and maps to human chromosome 5q31. Surprisingly, the human PP2 cDNAs and gene sequences display a single base deletion in the coding region. This frameshifting mutation predicts a truncated receptor of 290 amino acids without TM7. Transfection of COS-7 cells with several different human PP2 expression constructs failed to confirm any specific binding of I-125-PP, I-125-PYY, Or I-125-NPY to cell membranes. These data suggest that in mouse there are at least tyro PP receptors, Y4/PP1 and PP2, whereas in humans, PP2 is either functionally inactive or it has acquired a PP-independent function.