Functional Characterization of Three Mouse Formyl Peptide Receptors

doi:10.1124/mol.112.081315

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	Functional Characterization of Three Mouse Formyl Peptide Receptors
	He, Hui-Qiong 1; Liao, Dan 1; Wang, Zhen-Guo 3; Wang, Zhong-Li 1; Zhou, Hu-Chen 1; Wang, Ming-Wei2 ; Ye, Richard D.1,3
刊名	MOLECULAR PHARMACOLOGY
	2013-02
卷号	83 期号:2 页码:389-398
ISSN号	0026-895X
DOI	10.1124/mol.112.081315
文献子类	Article
英文摘要	The evolutionary relationship and functional correlation between human formyl peptide receptors (FPRs) and their mouse counterparts remain incompletely understood. We examined three members of the mouse formyl peptide receptor subfamily (mFprs) and found that they differ in agonist preference and cellular distributions. When stably expressed in transfected rat basophilic leukemia (RBL-2H3) cells, mFpr1 was readily activated by N-formylated peptides derived from Listeria monocytogenes (fMIVTLF), Staphylococcus aureus (fMIFL), and mitochondria (fMMYALF). In contrast, the Escherichia coli-derived fMLF was 1000-fold less potent. The aforementioned peptides were much less efficacious at mFpr2, which responded better to the synthetic hexapeptide WKYMVm, the synthetic agonists Quin-C1 (a substituted quinazolinone), and compound 43 (a nitrosylated pyrazolone derivative). Saturation binding assays showed that mFpr1 and mFpr2 were expressed at similar levels on the cell surface, although their affinity for N-formyl-Met-Leu-Phe-Ile-Ile-Lys-fluorescein isothiocyanate varied by more than 1000-fold [dissociation constant (K-d) values of 2.8 nM for mFpr1 and 4.8 mu M for mFpr2]). Contrary to these receptors, mFpr-rs1 responded poorly to all the previously mentioned peptides that were tested. Fluorescent microscopy revealed an intracellular distribution pattern of mFpr-rs1. On the basis of these results, we conclude that mFpr1 is an ortholog of human FPR1 with certain pharmacologic properties of human FPR2/ALX, whereas mFpr2 has much lower affinity for formyl peptides. The intracellular distribution of mFpr-rs1 suggests an evolutionary correlation with human FPR3.
资助项目	National Basic Research Program of China (973 Program)[2012CB518001] ; Chinese Postdoctoral Science Fund[12Z102060002]
WOS关键词	N-FORMYLPEPTIDE RECEPTOR ; PROTEIN-COUPLED RECEPTORS ; LISTERIA-MONOCYTOGENES ; BINDING-SITE ; LIGAND ; IDENTIFICATION ; FAMILY ; GENE ; FPR ; INFLAMMATION
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000313743700008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277756]
专题	国家新药筛选中心
通讯作者	Ye, Richard D.
作者单位	1.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 200031, Peoples R China 3.Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA;
推荐引用方式 GB/T 7714	He, Hui-Qiong,Liao, Dan,Wang, Zhen-Guo,et al. Functional Characterization of Three Mouse Formyl Peptide Receptors[J]. MOLECULAR PHARMACOLOGY,2013,83(2):389-398.
APA	He, Hui-Qiong.,Liao, Dan.,Wang, Zhen-Guo.,Wang, Zhong-Li.,Zhou, Hu-Chen.,...&Ye, Richard D..(2013).Functional Characterization of Three Mouse Formyl Peptide Receptors.MOLECULAR PHARMACOLOGY,83(2),389-398.
MLA	He, Hui-Qiong,et al."Functional Characterization of Three Mouse Formyl Peptide Receptors".MOLECULAR PHARMACOLOGY 83.2(2013):389-398.