Na+ regulation of formyl peptide receptor-mediated signal transduction in HL 60 cells. Evidence that the cation prevents activation of the G-protein by unoccupied receptors

Gierschik, Peter; Sidiropoulos, Dimitrios N.; Steisslinger, Marita; Jakobs, Karl H.

doi:10.1016/0922-4106(89)90031-x

Cited by 53 publications

(31 citation statements)

References 51 publications

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“…This result indicates that Asp-106, in addition to being important in NH 2 -terminal selectivity, may also be important for Na ϩ binding. Na ϩ competition with Arg-201 for interaction with Asp-106 might explain the Na ϩ regulation of ligand affinity observed by Giercheck et al (27). However, we were unable to detect any Na ϩ -dependent changes in fNle-LeuPhe-Nle-Tyr-Lys-fluorescein binding to CHO cells expressing wt FPR.…”

Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morecontrasting

confidence: 50%

“…It is believed that Na ϩ reduces FPR's affinity for fMLF by reducing the number of high affinity binding sites. This effect is cation-specific with NaCl Ͼ LiCl Ͼ KCl Ͼ choline chloride (27), suggesting that the ion pairing implied by our experiments might play a role in this inhibition. Therefore, we tested GTP␥S binding in CHO cells expressing wt FPR, D106N, R201A, and R205A, and compared their activity to that observed in CHO cells that did not express FPR.…”

Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morementioning

confidence: 79%

“…However, we were unable to detect any Na ϩ -dependent changes in fNle-LeuPhe-Nle-Tyr-Lys-fluorescein binding to CHO cells expressing wt FPR. No difference in binding was observed in the absence of Na ϩ , as compared with that seen in the presence of 100 mM Na ϩ , nor was there any difference in binding between 100 mM Na ϩ , 100 mM Li Giercheck et al (27). This result may reflect a difference between cation regulation of binding to intact cells versus that seen using membrane preparations (27).…”

Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morementioning

confidence: 89%

“…Effects of Na ϩ , Li ϩ , and K ϩ on GTP␥S binding to CHO cell membranes were determined using a buffer containing 75 mM Tris-Cl, pH 7.4, 12.5 mM Mg 2ϩ , 1 mM EDTA, 3 M GDP (Buffer B) to maintain the conditions previously described by Wenzel-Seifert et al (26) and Gierschik et al (27). Incubations were carried out at 30°C for 10 min, and GTP␥S binding never exceeded more than 10% of the total added to assure that binding was in the linear range.…”

Section: Methodsmentioning

confidence: 99%

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Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Mills

Miettinen

Cummings

et al. 2000

Journal of Biological Chemistry

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The formyl peptide receptor (FPR) 1 is a chemoattractant G protein-coupled receptor found on the surface of phagocytes. It is thought to play an important role in allowing phagocytic cells to recognize the presence of bacteria (1), which are a source of formyl peptides (2, 3). In addition, it recognizes and is activated by peptides derived from the GP-41 envelope protein of the human immunodeficiency virus type I (HIV-1) (4, 5). Recent studies with FPR-deficient mice indicate that they exhibit an increased susceptibility to infection with Listeria monocytogenes and that neutrophils from these knockout mice fail to exhibit chemotaxis in response to fMLF (6).The formyl peptide receptor was originally identified based on its ability to bind the formylated peptide, fMLF (1). Six different chemotactic peptides have been isolated from Escherichia coli, including fMLF (3), but the only similarity between them was an NH 2 -terminal formyl methionine, suggesting that this moiety is highly important in binding to FPR. Studies using NH 2 -terminal analogs of MLF had indicated that the formyl group had significant effects on the ligand binding affinity for neutrophil FPR. Free amino, desamino, and acetylated derivatives of MLF were all 3000-fold lower in affinity than fMLF (7). Substitution of the formyl group of fMLF with a tert-butyloxycarbonyl group made the ligand an antagonist of low affinity (8). However, the formyl group may be less essential than originally thought. N-Butyloxycarbonyl MLF exhibits agonist activity (9) with an affinity similar to fMLF, and phenyl and tolyl isourea derivatives of MLF exhibit activity similar to or greater than fMLF (10). On the other hand, most aliphatic isourea derivatives of MLF exhibit low affinity antagonist activity similar to what is observed with tert-butyloxycarbonyl-MLF (10). This difference indicates that FPR exhibits a high degree of specificity for NH 2 -terminal modifications of MLF, and that the specificity for the formyl group is not absolute. In addition, other reports have indicated that non-formylated pentapeptides can activate FPR. Both MNleLFF and MMWLL are effective activators of FPR (11,12), and acetyl-MNleLFF is more potent than fMLF (12), indicating that these pentapeptides exhibit somewhat different NH 2 -terminal specificities than does MLF.We have previously shown that the formyl peptide binding site maps to several membrane-spanning regions (13-14). Ten residues which affect fMLF binding have been mapped to transmembrane domains II-VII (13), including residues Leu-78 (II-17, helix II, residue 17 of 26 transmembrane-spanning residues in the nomenclature used throughout this text), Asp-106 (III-8), Leu-109 (III-11), Thr-157 (IV-18), Arg-201 (V-2), Ile-204 (V-5), , , and Phe-291 (VII-11). In addition, photo-cross-linking data suggest that the leucine side chain of fMLF is probably located close to FPR 93 VRK 95 , which is at the COOH terminus of helix II (14).Human FPR is one of three receptors in the human FPR family, which includes, FPR, the lipoxin A 4 re...

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Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morecontrasting

confidence: 50%

Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morementioning

confidence: 79%

Section: D106n and R201a Bind A Peptide Derived From Hiv (Dp178) Morementioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Mills

Miettinen

Cummings

et al. 2000

Journal of Biological Chemistry

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“…[16]. Pertussis toxin was isolated from the supernatant of Bordetella pertussis suspensions as in [17].…”

Section: Introductionmentioning

confidence: 99%

Interaction of small G proteins with photoexcited rhodopsin

et al. 1990

Self Cite

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Bovine rod outer segment (ROS) membranes contain in addition to the heterotrimeric G protein transducin, several small GTP-binding proteins (23-27 kDa). Furthermore, these membranes contain two substrate proteins (about 22 and 24 kDa) for botulinurn C3 ADP-ribosyltransferase known to ADP-ribosylate small G proteins in any mammalian cell type studied so far. Most interestingly, P*P]ADP-ribosylation of ROS membrane small G proteins by C3 is regulated by light and guanine nucleotides in a manner similar to pertussis toxin-catalyzed[32P]ADP-ribosy1ation of the a-subunit of transducin.These findings suggest that not only the heterotrimeric G protein transducin but also the C3 substrate small G proteins present in ROS membranes interact with photoexcited rhodopsin and thus contribute to its signalling action.GTP-binding protein; Rhodopsin; Botulinum C3 ADP-ribosyl-transferase; Transducin; (Bovine rod outer segment)

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Allosteric modulation of the rat adenosine A₁ receptor: Differential effects on agonist and antagonist binding

Kourounakis

Visser

Groote

et al. 2000

Drug Development Research

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The interaction of 2-amino-3-benzoyl-thiophene derivative, PD81,723, as well as other G protein-coupled receptor (GPCR)-modulating agents such as suramin (SUR), N-ethylmaleimide (NEM), GTP, and NaCl with the rat adenosine A 1 receptor was investigated using kinetic, saturation, as well as displacement experiments of various agonists, partial agonists or antagonists. PD81,723 enhanced agonist (CPA, R-PIA, NECA) binding ~2-fold, while its effect on CPA binding was increased (4-11-fold) with other modulators present. In contrast, binding of antagonists (DPCPX, CPT, N-0840) was inhibited, while binding of partial agonists (8BCPA, MeSCPA) remained uninfluenced. The effect of PD81,723 is consistent with shifting A 1 receptors to an "active" (R*) state with high affinity for agonists and low for antagonists. Further, all described allosteric modulators influenced both agonist and antagonist binding. The IC 50 values observed for the agonist CPA, ranging from 4.7 nM in the presence of PD81,723 to a high value of 2.9 µM in the combined presence of NEM, NaCl, and GTP, represented a greater than 600-fold affinity shift. We suggest that the latter micromolar IC 50 value may approximate CPA's "true" affinity (K A ) for the rat adenosine A 1 receptor. Drug Dev. Res. 51:207-215, 2000.

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Na+ regulation of formyl peptide receptor-mediated signal transduction in HL 60 cells. Evidence that the cation prevents activation of the G-protein by unoccupied receptors

Cited by 53 publications

References 51 publications

Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Interaction of small G proteins with photoexcited rhodopsin

Allosteric modulation of the rat adenosine A₁ receptor: Differential effects on agonist and antagonist binding

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Na+ regulation of formyl peptide receptor-mediated signal transduction in HL 60 cells. Evidence that the cation prevents activation of the G-protein by unoccupied receptors

Cited by 53 publications

References 51 publications

Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Characterization of the Binding Site on the Formyl Peptide Receptor Using Three Receptor Mutants and Analogs of Met-Leu-Phe and Met-Met-Trp-Leu-Leu

Interaction of small G proteins with photoexcited rhodopsin

Allosteric modulation of the rat adenosine A1 receptor: Differential effects on agonist and antagonist binding

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Product

Resources

About

Allosteric modulation of the rat adenosine A₁ receptor: Differential effects on agonist and antagonist binding