Identification, localization and receptor characterization of novel mammalian substance P-like peptides
Identification, localization and receptor characterization of novel mammalian substance P-like peptides
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DOI：
10.1016/s0378-1119(02)00861-2
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发表时间：
2002-08-21
期刊：
影响因子：
3.5
通讯作者：
Liu, QY
中科院分区：
文献类型：
--
作者：
Kurtz, MM;Wang, RP;Liu, QY
血激肽-1（HK-1）是一种新的P物质（SP）样肽，由最近在小鼠B细胞中鉴定的前速激肽原C（PPT-C）基因编码，并显示为B细胞发育的潜在重要调节剂（Nat.Immunol.1（2000）392）。我们现在已经分离并鉴定了人和大鼠的PPT-C的直系同源物，并检测了人和小鼠HK-1对三种速激肽受体神经激肽-1-3（NK 1 -3）的活性。大鼠PPT-C多肽与小鼠PPT-C高度同源，并含有相同的加工位点以产生预测的HK-1。人PPT-C多肽也与小鼠PPT-C同源，然而，它在预测的HK-1肽的氨基末端含有两个潜在的单碱基切割位点，而不是一个单一的二元切割位点。因此，人PPT-C具有产生全长预测HK-1以及截短形式（HK-1（4-11））的潜力。聚合酶链反应分析表明，人类和小鼠PPT-C在各种组织中表达，在两种物种的皮肤和小鼠大脑中检测到强烈的信号。结合和功能分析表明，人类和小鼠HK-1肽在其对三种NK受体的总体活性谱中与SP几乎相同，对NK 1受体具有最强的亲和力。结果表明，PPT-C编码的另一个高亲和力的配体的NK 1受体，这可能发挥重要作用，在介导的一些生理作用，以前分配给NK 1受体。(C)2002 Elsevier Science B. V.保留所有权利。
Hemokinin-1 (HK-1) is a novel substance P (SP)-like peptide that is encoded by the preprotachykinin C (PPT-C) gene recently identified in mouse B cells and shown to be a potentially important regulator of B cell development (Nat. Immunol. 1 (2000) 392). We have now isolated and characterized the human and rat orthologs of PPT-C and examined activities of human and mouse HK-1 on the three tachykinin receptors, neurokinin-1-3 (NK1-3). The rat PPT-C polypeptide is highly homologous to mouse PPT-C and contains the same processing sites to generate predicted HK-1. The human PPT-C polypeptide is also homologous to mouse PPT-C, however, it contains two potential monobasic cleavage sites rather than a single dibasic cleavage site at the amino-terminal end of the predicted HK-1 peptide. Thus, human PPT-C has the potential to generate full length predicted HK-1 as well as a truncated version (HK-1(4-11)). Polymerase chain reaction analysis revealed that both human and mouse PPT-C were expressed in a variety of tissues with strong signals detected in the skin of both species and in the mouse brain. Binding and functional analysis indicated that human and mouse HK-1 peptides were nearly identical to SP in their overall activity profile on the three NK receptors with the most potent affinity for the NK1 receptor. The results indicate that PPT-C encodes another high affinity ligand of the NK1 receptor which may play an important role in mediating some of the physiological roles previously assigned to the NK1 receptor. (C) 2002 Elsevier Science B.V. All rights reserved.