Identification, localization and receptor characterization of novel mammalian substance P-like peptides
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- 作者：Kurtz ; Marc M. ; Wang ; Ruiping ; Clements ; Michelle K. ; Cascieri ; Margaret A. ; Austin ; Christopher P. ; et. al.
- 关键词：Hemokinin ; Substance P ; Neurokinin receptors ; Human ; Expression profiling ; HK-1 ; hemokinin-1 ; mHK-1 ; mouse HK-1 ; hHK-1 ; human HK-1 ; rHK-1 ; rat HK-1 ; FLIPR ; Fluorescence Imaging Plate Reader ; PPT-C ; preprotachykinin C ; SP ; substance P ; NKA ; neurokinin A ; N
- 刊名：Gene
- 出版年：2002
- 出版时间：August 21, 2002
- 年：2002
- 卷：296
- 期：1-2
- 页码：205-212
- 全文大小：317 K
文摘
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.