Larhammar D
Department of Medical Pharmacology, Uppsala University, Sweden.
Regul Pept. 1996 Sep 16;65(3):165-74. doi: 10.1016/0167-0115(96)00110-3.
The NPY (neuropeptide Y) family of neuroendocrine peptides consists of NPY, PYY (peptide YY) and PP (pancreatic polypeptide). Several receptors have been characterized pharmacologically of which three have now been cloned. All three belong to the superfamily of receptors that couple to G proteins and all three cause inhibition of cAMP accumulation. Receptor subtypes Y1 and Y2 bind both NPY and PYY. Surprisingly, Y1 and Y2 share only 31% overall sequence identity, the lowest percentage reported for receptors that bind the same peptide ligand. Nevertheless, each subtype is 94% identical between human and rat, suggesting a slow rate of change. These observations suggest that Y1 and Y2 started to diverge from one another very long ago, possibly before the origin of vertebrates. The PP receptor, called PP1 or Y4, is 42% identical to the Y1 receptor (57% in the transmembrane regions) and is one of the most rapidly evolving receptors with only 75% overall identity between man and rat. Interestingly, this receptor's preferred ligand, PP, also evolves extremely rapidly. The PP receptor also differs between man and rat in tissue distribution and binding properties. The Y1 and PP receptors bind to both termini of their ligands whereas Y2 mainly interacts with the C-terminal part. Thus, within the same family there are highly conserved receptors and peptide ligands as well as one rapidly evolving receptor and ligand.
神经内分泌肽的神经肽Y（NPY）家族由NPY、肽YY（PYY）和胰多肽（PP）组成。已经从药理学上对几种受体进行了表征，其中三种现已被克隆。这三种受体均属于与G蛋白偶联的受体超家族，并且都能抑制环磷酸腺苷（cAMP）的积累。受体亚型Y1和Y2既能结合NPY，也能结合PYY。令人惊讶的是，Y1和Y2的总体序列同一性仅为31%，这是结合相同肽配体的受体中报道的最低百分比。然而，每种亚型在人和大鼠之间的同一性为94%，这表明其变化速率较慢。这些观察结果表明，Y1和Y2在很久以前就开始相互分化，可能在脊椎动物出现之前。PP受体，称为PP1或Y4，与Y1受体有42%的同一性（跨膜区域为57%），是进化最快的受体之一，在人和大鼠之间的总体同一性仅为75%。有趣的是，该受体的首选配体PP也进化得极快。PP受体在人和大鼠之间的组织分布和结合特性也有所不同。Y1和PP受体与其配体的两个末端结合，而Y2主要与C末端部分相互作用。因此，在同一家族中，既有高度保守的受体和肽配体，也有一个快速进化的受体和配体。
