High impact information on FPRL2

• The peptide binds and activates FPRL2 in the low nanomolar range, which triggers intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases through the G(i) class of heterotrimeric G proteins [1].
• Therefore, F2L appears as a new natural chemoattractant peptide for DCs and monocytes, and the first potent and specific agonist of FPRL2 [1].
• The receptors mediating monocyte activation were identified as FPRL1 and the monocyte-specific orphan receptor FPRL2 [2].
• Because extracellular AnxA1 has been shown to regulate leukocyte migratory events through interactions with n-formyl peptide receptors (nFPRs), we examined the expression of FPR-1, FPRL-1, and FPRL-2 in SKCO-15 cells by reverse transcriptase-PCR and identified expression of all three receptors in this cell line [3].
• In contrast, desensitization with WKYMVm, which also binds FPRL2, markedly inhibited the response to both molecules [4].

Biological context of FPRL2

• Two structural homologues of the FMLP receptor, clones 81 (FPRH1) and 82 (FPRH2), were identified, which similarly map to chromosome 19 [5].
• Thus, the regulation of FPRL2 gene expression in vivo differs from FPR1 and FPRL1 [6].

Anatomical context of FPRL2

• Both FPR and FPRL1 cDNA cross-hybridize under high stringency conditions with a third gene, designated as FPRL2, which does not appear to be expressed in neutrophils [7].
• These observations identify the annexin 1 peptide as the first endogenous ligand of FPRL2 and indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family [8].
• In contrast to FPRL1, FPRL2 was already phosphorylated in the absence of agonist and not evenly distributed in the plasma membrane of unstimulated cells [9].
• Taken together, the results indicate that neutrophils are activated by WKYMVM through FPRL1 and that FPRL2 is a chemotactic receptor transducing signals in myeloid cells [9].
• Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation [10].

Associations of FPRL2 with chemical compounds

• In addition, formyl-Met-Leu-Phe (a FPR ligand), Trp-Lys-Tyr-Met-Val-Met, Hp(2-20) peptide, and F2L (three FPRL2 ligands) inhibited LPS-induced IL-12 production in DCs [11].
• The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2 [9].
• The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met inhibits human monocyte-derived dendritic cell maturation via formyl peptide receptor and formyl peptide receptor-like 2 [11].

Other interactions of FPRL2

• Recently F2L, a heme-binding protein fragment peptide, has been reported as an FPRL2-selective endogenous agonist [12].

References