Trp-Arg-Trp-Trp-Trp-Trp antagonizes formyl peptide receptor like 2-mediated signaling.
Although formyl peptide receptor like 2 (FPRL2) has been regarded as an important classical chemoattractant receptor, its functional role and signaling pathway have not been fully investigated, because of the lack of its specific ligand. Recently F2L, a heme-binding protein fragment peptide, has been reported as an FPRL2-selective endogenous agonist. In the present study, we examined the effect of Trp-Arg-Trp-Trp-Trp-Trp-CONH2 (WRWWWW, WRW4), on F2L-induced cell signaling. WRW4 inhibited the activation of FPRL2 by F2L, resulting in the complete inhibition of intracellular calcium increase and chemotactic migration induced by F2L. WRW4 also completely inhibited F2L-induced NF-kappaB activation in FPRL2-transfected HEK293 cells. WRW4 specifically inhibited F2L-induced intracellular calcium increase and chemotactic migration in mature monocyte-derived dendritic cells, which express FPRL2 but not the other FPR family. Taken together, WRW4 is the first FPRL2 antagonist and is expected to be useful in the study of FPRL2 signaling and in development of drugs against FPRL2-related cellular responses.
Shin
Eun Ha
EH
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Lee
Ha-Young
HY
Kim
Sang Doo
SD
Jo
Seong Ho
SH
Kim
Mi-Kyoung
MK
Park
Kyoung Sun
KS
Lee
Hyuck
H
Bae
Yoe-Sik
YS
D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D000081062:Heme-Binding Proteins; D006420:Hemeproteins / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
D002352:Carrier Proteins; C469985:FPR3 protein, human; D000081062:Heme-Binding Proteins; D006420:Hemeproteins; D016328:NF-kappa B; D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; C509690:tryptophyl-arginyl-tryptophyl-tryptophyl-tryptophyl-tryptophanamide; D002118:Calcium