The Chemotactic Peptide Receptor: A Model for Future Understanding of Chemotactic Disorders

Ra, Allen; Ae, Traynor; Gm, Omann; Jesaitis, AJ

doi:10.1016/s0889-8588(18)30630-0

Cited by 31 publications

(23 citation statements)

References 162 publications

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“…The formylated tripeptide fMet-Leu-Phe (FMLP) is a potent activator of neutrophil function (Allen et al, 1988). Signal transduction from the receptor for this chemotactic peptide is mediated by pertussis toxin sensitive GTP binding proteins (Krause et al, 1985).…”

Section: Introductionmentioning

confidence: 98%

“…Binding of the ligand alters membrane potential (Lazzari et al, 1990) and activates phospholipase C (PLC) with subsequent calcium mobilization and influx (Krause et al, 1985;Smith et al, 1985;Demaurex et al, 1992a). This ultimately leads to chemotaxis, secretion and superoxide production (Allen et al, 1988). Cloning of FMLP binding proteins revealed the existence of two allelic cDNA sequences in the human myeloid cell line HL-60 (Boulay et al, 1990a).…”

Section: Introductionmentioning

confidence: 99%

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Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.

Láng

Boulay

et al. 1993

The EMBO Journal

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In neutrophils fMet-Leu-Phe activates phospholipase C via a pertussis toxin sensitive G-protein and induces granule secretion. We have transfected a human cDNA sequence encoding the tMet-Leu-Phe receptor into the insulin secreting cell line RINm5F to study receptor-effector coupling with special regard to secretion. Stable overexpression resulted in membrane hyperpolarization, reduction of cAMP accumulation and inhibition of insulin secretion upon exposure of cells to fMet-Leu-Phe with EC50 values in the pmol range. As in the neutrophil, nanomolar concentrations of ligand induced membrane depolarization and activation of phospholipase C, with subsequent mobilization and influx of calcium. In permeabilized cells the inhibitory effect of fMet-Leu-Phe on secretion was partially retained indicating a direct action of the fMet-Leu-Phe receptor on exocytosis. Pertussis toxin abolished the effects of fMet-Leu-Phe. Our results suggest conserved coupling from fMet-Leu-Phe receptor to pertussis toxin sensitive transducers analogous to the mechanism in neutrophils. However, the net biological effect of receptor activation is determined by additional factors intrinsic to the host cell.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.

Láng

Boulay

et al. 1993

The EMBO Journal

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“…Defined chemotactic factors include C5a, a complement proteolytic fragment, leukotriene B4 (LTB4), an araehidonate metabolite, platelet-activating factor (PAF), certain products of bacterial protein synthesis (i.e. formylmethionyl peptides) and a family of chemotactic cytokines including interleukin-8 (reviewed in [1,2]). …”

Section: Introductionmentioning

confidence: 99%

“…While much is known of how this receptor initiates cellular activation [1,2], the precise mechanisms by which chemoattractant r~eptors initiate migratory versus cytotoxie activities remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Functional high efficiency expression of cloned leucocyte chemoattractant receptor cDNAs

et al. 1992

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Human kidney 293 TSA cells were transfected by a calcium phosphate method with human formylpeptide and CSa re.~ptor cDNAs with higli efficiency. Formylpeptide receptor positive transfectants expressed a total of 968.000 ± 34,000 receptors per cell with two affinity stat©s (Kds of ca. 0.43 nM and 39 riM), which in the presence of 100/~M GTP~,S decreased by ca. 4-fold the number of high-affinity sites. The ligand binding pharmacology of cloned and expressed formylpeptide r~ptors were indistinguishable from endogenous receptors on human neutrophils. Expres.~d formylpcptide and CSa receptors were functionally active in mobilizing intracellular calcium via a pertussis toxin sensitive mechanism with an £Ds0 for formylpeptid¢ of ca. 0.5-1.0 nM. This expression system, in which receptor expression can be monitored by flow cytometrie methods and in which intracellular calcium responses are measurable, unlike in the more popular COS-7 cell expression system, will provide a useful basis for the analysis of chemoattractant receptor structure-function relationships.

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“…At higher concentrations, chemoattractants stimulate the cell's cytotoxic responses (activation ofthe respiratory burst and exocytosis of lysosomal enzymes). Specific receptors for chemotactic factors are present on phagocytic leukocytes (i.e., neutrophils and mononuclear phagocytes) and initiate signal transduction via a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein (G protein) to activate phospholipase C, resulting in the formation of diacylglycerol and inositol phospholipids (2,3). The best-characterized chemoattractant receptor is the one that binds formylpeptides.…”

mentioning

confidence: 99%

Receptor class desensitization of leukocyte chemoattractant receptors.

Didsbury

Uhing

Tomhave

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

129

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The Chemotactic Peptide Receptor: A Model for Future Understanding of Chemotactic Disorders

Cited by 31 publications

References 162 publications

Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.

Conserved transducer coupling but different effector linkage upon expression of the myeloid fMet-Leu-Phe receptor in insulin secreting cells.

Functional high efficiency expression of cloned leucocyte chemoattractant receptor cDNAs

Receptor class desensitization of leukocyte chemoattractant receptors.

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