Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/18213
Title: The N-terminal domain of human hemokinin-1 influences functional selectivity property for tachykinin receptor neurokinin-1
Authors: Mou, L
Xing, Y
Kong, Z
Zhou, Y
Chen, Z
Wang, R
Keywords: ERK1/2
Functional selectivity
Hemokinin-1
Neurokinin-1 receptor
NF-?eB
Issue Date: 2011
Publisher: Elsevier
Source: Biochemical pharmacology, 2011, v. 81, no. 5, p. 661-668 How to cite?
Journal: Biochemical pharmacology 
Abstract: Human hemokinin-1 (hHK-1) is a substance P-like tachykinin peptide preferentially expressed in non-neuronal tissues. It is involved in multiple physiological functions such as inflammation, hematopoietic cells development and vasodilatation via the interaction with tachykinin receptor neurokinin-1 (NK1). To further understand the intracellular signal transduction mechanism under such functional multiplicity, current study was focused on the differential activation of Gs and Gq pathways by hHK-1 and its C-terminal fragments, which is termed as functional selectivity. We demonstrated these hHK-1 and related peptide fragments can independently activate Gs and Gq pathways, showing a relative bias toward Gq over Gs pathway. The T1, K3 and Q6 of hHK-1 might play roles in the activation of adenylate cyclase mediated by Gs, while having negligible effect on Gq mediated intracellular calcium release. The stepwise truncation of N-terminal amino acid of hHK-1 caused gradual decrease in ERK1/2 phosphorylation level and NF-?eB activity. However, it had little influence on the induction of NK1 receptor desensitization and internalization. Taken together these data support that hHK-1 and its C-terminal fragments are human NK1 receptor agonists with different functional selectivity properties and that such functional selectivity leads to differential activation of downstream signaling and receptor trafficking.
URI: http://hdl.handle.net/10397/18213
ISSN: 0006-2952
EISSN: 1873-2968
DOI: 10.1016/j.bcp.2010.12.007
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