The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor

R. He, L. Tan, Darren D Browning, Ming Wang Ji Ming Wang, R. D. Ye

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Formyl peptides are potent neutrophil chemoattractants. In humans and rabbits, the formyl peptide receptor (FPR) binds N-formyl-Met-Leu-Phe (fMLF) with high affinity (K(d) ≃ 1 nM). The mouse FPR (mFPR) is a low-affinity receptor for fMLF (K(d) 100 nM); therefore, other agonists for this receptor may exist. Using mFPR-transfected rat basophilic leukemia cells, we found that a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a potent agonist for mFPR. WKYMVm induced calcium mobilization with an EC50 of 1.2-1.5 nM. Optimal chemotaxis was achieved with 1 nM of WKYMVm, but it required 100 nM of fMLF. WKYMVm stimulated rapid and potent phosphorylation of the mitogen-activated protein kinases extracellular signal-related kinases 1 and 2 when used at 50 nM. Pertussis toxin only partially blocked calcium mobilization and production of inositol 1,4,5-trisphosphate in the stimulated mFPR cells, suggesting the possibility that this receptor couples to Gα proteins other than Gi and Go. Competitive binding and desensitization data suggest that both peptides interact with the same receptor but may use nonoverlapping binding sites because WKYMVm was unable to effectively displace [3H]fMLF bound to mFPR. These results provide evidence for the presence of an alternative potent agonist for mFPR, and suggest a potential usage of WKYMVm for probing the ligand-receptor interactions with the murine formyl peptide receptor homologs.

Original languageEnglish (US)
Pages (from-to)4598-4605
Number of pages8
JournalJournal of Immunology
Volume165
Issue number8
StatePublished - Oct 15 2000
Externally publishedYes

Fingerprint

Formyl Peptide Receptor
Peptides
Calcium
Inositol 1,4,5-Trisphosphate
Competitive Binding
Chemotactic Factors
Pertussis Toxin
Chemotaxis
Mitogen-Activated Protein Kinases
GTP-Binding Proteins
Leukemia
Neutrophils
Phosphotransferases
Binding Sites
Phosphorylation
Rabbits
Ligands

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor. / He, R.; Tan, L.; Browning, Darren D; Ji Ming Wang, Ming Wang; Ye, R. D.

In: Journal of Immunology, Vol. 165, No. 8, 15.10.2000, p. 4598-4605.

Research output: Contribution to journalArticle

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abstract = "Formyl peptides are potent neutrophil chemoattractants. In humans and rabbits, the formyl peptide receptor (FPR) binds N-formyl-Met-Leu-Phe (fMLF) with high affinity (K(d) ≃ 1 nM). The mouse FPR (mFPR) is a low-affinity receptor for fMLF (K(d) 100 nM); therefore, other agonists for this receptor may exist. Using mFPR-transfected rat basophilic leukemia cells, we found that a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a potent agonist for mFPR. WKYMVm induced calcium mobilization with an EC50 of 1.2-1.5 nM. Optimal chemotaxis was achieved with 1 nM of WKYMVm, but it required 100 nM of fMLF. WKYMVm stimulated rapid and potent phosphorylation of the mitogen-activated protein kinases extracellular signal-related kinases 1 and 2 when used at 50 nM. Pertussis toxin only partially blocked calcium mobilization and production of inositol 1,4,5-trisphosphate in the stimulated mFPR cells, suggesting the possibility that this receptor couples to Gα proteins other than Gi and Go. Competitive binding and desensitization data suggest that both peptides interact with the same receptor but may use nonoverlapping binding sites because WKYMVm was unable to effectively displace [3H]fMLF bound to mFPR. These results provide evidence for the presence of an alternative potent agonist for mFPR, and suggest a potential usage of WKYMVm for probing the ligand-receptor interactions with the murine formyl peptide receptor homologs.",
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