Studies on fMLP-receptor interaction and signal transduction pathway by means of fMLP-OMe selective analogues

Fabbri, Elena; Spisani, Susanna; Barbin, Laura; Biondi, Carla; Buzzi, Marco; Traniello, Serena; Zecchini, Giampiero Pagani; Ferretti, Maria Enrica

doi:10.1016/s0898-6568(00)00075-9

Cited by 24 publications

(16 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The binding followed a saturating curve with a calculated K d of 36 nM (Figure 3A, inset; Table 2). These results were well within the range of what was observed previously at low temperatures [23]. Fabbri et al [23] reported two fMLP-binding sites on neutrophils with K d1 = 25 nM and K d2 = 1.5 µM in assays performed at 4 • C.…”

Section: Characterization Of Fmlp Receptors On Neutrophilssupporting

confidence: 89%

“…Neutrophils (5 × 10 6 cells/assay) were incubated in 200 µl of RPMI 1640 containing 0.5 % (w/v) BSA for 15 min at 37 • C [23], in the presence of increasing concentrations of [ 3 H]fMLP (0-6 µM). To reach concentrations higher than 8 × 10 − 7 M, [ 3 H]fMLP was mixed with unlabelled fMLP.…”

Section: Binding Experimentsmentioning

confidence: 99%

“…In the present study, we have investigated the coupling of each of the two fMLP receptor subtypes with L-plastin phosphorylation. We characterized the two fMLP receptor subtypes in human neutrophils [23] and determined the conditions to study their individual downstream effects. We show that L-plastin phosphorylation occurs in response to either receptor and that distinct signal-transduction intermediates couple the individual receptor subtypes with L-plastin.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

Paclet

Davis²,

Kotsonis³

et al. 2004

Biochemical Journal

View full text Add to dashboard Cite

We investigated the coupling of the fMLP (N -formyl-L-methionyl-L-leucyl-L-phenylalanine; 'chemotactic peptide') receptor with phosphorylation of the actin-binding protein L-plastin in neutrophils. Using two-dimensional IEF (isoelectric focusing)/PAGE and MALDI-TOF (matrix-assisted laser desorption ionization-time-of-flight)-MS, L-plastin was identified as a major phosphoprotein in fMLP-stimulated neutrophils whose phosphorylation was dependent on phosphoinositide 3-kinase, PLD (phospholipase D) and PKC (protein kinase C) activity. Two fMLP receptor subtypes were identified in neutrophils, characterized by a distinct sensitivity to fMLP and antagonistic peptides. Both receptor subtypes induced the phosphorylation of L-plastin. L-plastin phosphorylation induced by low-affinity fMLP receptors involves an action of phosphoinositide 3-kinase, PLD and PKC isotypes. In contrast, none of these intermediates are utilized by high-affinity fMLP receptors in the phosphorylation of L-plastin. However, the PKC inhibitor Ro-31-8220 inhibits L-plastin phosphorylation induced by the high-affinity fMLP receptor. Thus, an as yet unknown Ro-31-8220-sensitive kinase regulates L-plastin phosphorylation in response to the high-affinity fMLP receptor. The results suggest a model in which receptor subtypes induce a similar endpoint event through different signal-transduction intermediates. This may be relevant in the context of cell migration in which one receptor subpopulation may become desensitized in a concentration gradient of chemoattractant.

show abstract

Section: Characterization Of Fmlp Receptors On Neutrophilssupporting

confidence: 89%

Section: Binding Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

Paclet

Davis²,

Kotsonis³

et al. 2004

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…To characterise further FPR interactions in phagocytes and subsequent cellular activation, several fMLP-OMe analogues have been synthesized [26] including for-Met-Leu-Cys(OMe)-Cys-Leu-Met-fpr, which binds to FPR1 [27]. Recently, fMLP-OMe analogues with receptor affinity greater than that of the parent fMLP-OMe have been synthesized, creating the potential for use as carriers for drugs [11].…”

Section: Fpr Pharmacology Agonistsmentioning

confidence: 99%

Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia–reperfusion injury?

Gavins

2010

Trends in Pharmacological Sciences

View full text Add to dashboard Cite

Ischaemia-reperfusion (I/R) injury is a common feature of several diseases associated with high morbidity and mortality, such as stroke and myocardial infarction. The damaged tissue displays cardinal signs of inflammation and microvascular injury that, unless resolved, lead to long-term tissue damage with associated dysfunction. Current therapies are limited and are often associated with many side effects. Increasing evidence suggests that members of the formyl peptide receptor (FPR) family, in particular human FPR2/ALX, might have an important role in the pathophysiology of I/R injury. It was recently demonstrated that several peptides and non-peptidyl small-molecule compounds have anti-inflammatory and pro-resolving properties via their action on members of the FPR family. Here I review this evidence and suggest that FPR ligands, particularly in the brain, could be novel and exciting anti-inflammatory therapeutics for the treatment of a variety of clinical conditions, including stroke.

show abstract

“…The retroisomer of fMLP, i.e., CHO–Phe–Leu–Met–NH 2 and its D analogs were found to be 100 to 10,000 times less active 74. Many other formyl peptides were also examined recently, for biological activities;75–95…”

Section: Discussionmentioning

confidence: 99%

Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP

Rathore

2005

Biopolymers

View full text Add to dashboard Cite

Conformations of three analogs of for-L-Met-L-Leu-L-Phe-OH (fMLP), which initiates inflammatory response by interaction with the formyl peptide receptor (FPR), have been investigated by the application of the X-ray crystallographic technique. The investigated analogs of fMLP peptides are as follows: for-L-Met-1-amino-1-cyclooctane-carbonyl(Ac8c)-L-Phe-OMe; for-L-Met-L-Leu-L-p-iodo-Phe-OH; and for-L-Met-di-n-propylglycyl(Dpg)-L-Phe-OMe. The peptide backbone in and is constrained at position of fMLP by the introduction of Calpha,alpha-disubstituted glycines. In peptide, Phe-OMe is substituted by p-iodo-Phe-OH. Crystal structures reveal an overall folded conformation adopted by and. The former is folded in the type II beta-turn, which is stabilized by an intramolecular 1<--4 (formyl) C==O...H--N (Phe) hydrogen bond, whereas the latter is folded in an open turn without any intramolecular hydrogen bond. On the other hand, peptide has an extended conformation, and two different molecules in a crystallographic asymmetric unit form an antiparallel beta-sheet-like structure. In and, residues Ac8c and Dpg adopt left-handed helical and fully extended (C5) conformations, respectively. The cyclooctane ring in Ac8c acquires a boat-chair conformation. Crystal packing of is characterized by the association of aliphatic-aromatic rings via a C--H...pi interaction. In the crystal of, contrary to the usual observations, peptides are interlinked via networks of head-to-tail hydrogen bond and pi...pi interactions, which are generally observed to be mutually exclusive. The structure-function mechanism of the ligand-receptor interaction is discussed.

show abstract

Studies on fMLP-receptor interaction and signal transduction pathway by means of fMLP-OMe selective analogues

Cited by 24 publications

References 24 publications

N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

N-Formyl peptide receptor subtypes in human neutrophils activate l-plastin phosphorylation through different signal transduction intermediates

Are formyl peptide receptors novel targets for therapeutic intervention in ischaemia–reperfusion injury?

Conformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP

Contact Info

Product

Resources

About