title: Relationship of ligand-receptor dynamics to actin polymerization in RBL-2H3 cells transfected with the human formyl peptide receptor.
abstract: The human formyl peptide receptor (FPR) expressed in RBL-2H3 transfectants (RBL[FPR]) behaves qualitatively like the FPR expressed by neutrophils except that it causes sustained F-actin accumulation and cell shape change responses on formyl peptide stimulation. These sustained responses were not accounted for by changes in the transfected receptor's ability to interact with ligand or by receptor density. Signal transduction pathways of transfected and neutrophil FPRs are apparently similar. In transfected cells, dissociation of ligand is sensitive to guanine nucleotide, the G protein is pertussis toxin-sensitive, FPR and G protein appear to be precoupled, the F-actin response is stimulated with the same dose-response profile as in neutrophils, and the F-actin accumulation response is directly regulated by the FPR, even long after initial stimulation. Potentially significant differences between neutrophil and transfected FPR were found when receptor processing was measured. In neutrophils, practically 100% of the FPR is converted to forms that dissociate slowly from ligand and are inactive in signal transduction within 2 min of ligand stimulation. By contrast, 20% or more of transfected FPR remains rapidly dissociating even 5 min after stimulation. Although 80% of neutrophil FPR is internalized by 5 min after stimulation, transfected FPR appears to plateau at 50-60% internalized. Because actin responses in neutrophils are regulated by a small number of active receptors, the inefficiency of receptor inactivation in RBL(FPR) transfectants may account for the prolonged F-actin accumulation response.
authors.affiliation: Cancer Research and Treatment Center and Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Hall
authors.forename: B S
authors.initials: BS
authors.lastname: Wilson
authors.forename: J R
authors.initials: JR
authors.lastname: Pfeiffer
authors.forename: J M
authors.initials: JM
authors.lastname: Oliver
authors.forename: L A
authors.initials: LA
authors.lastname: Sklar
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D015471:Leukemia, Basophilic, Acute; D046911:Macromolecular Substances; D008855:Microscopy, Electron, Scanning; D018715:Microscopy, Video; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D000199:Actins; D046911:Macromolecular Substances; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium