title: The influence of actin microfilaments on signaling by the receptor with high-affinity for IgE.
abstract: Aggregation of the receptors with high-affinity for IgE (FcRI) stimulates a variety of cellular responses, but excessive aggregation inhibits such responses. Actin filaments have been implicated in the inhibitory phenomenon because disrupting the filaments enhances the cellular reactions stimulated by the aggregated receptors. To clarify further the molecular mechanism and physiological importance of the actin-mediated inhibition, we assessed the effect of inhibitors of actin polymerization on the initial signaling events of mast cells alternatively stimulated by nitrophenyl ligands that dissociate slowly (high-affinity) or rapidly (low-affinity) from receptor-bound anti-dinitrophenyl IgE. The inhibitors amplified the phosphorylation of FcRI and of Syk induced by addition of either ligand but at physiological temperatures, the augmentation of the response to the low-affinity ligand was especially exaggerated. The effect of actin is on the earliest events, and although the molecular mechanism(s) by which the filaments regulate the intensity of proximal signaling remains unclear, several possibilities have been excluded. That the inhibitors only minimally augment the responses stimulated by preformed dimers of IgE, and in general show smaller effects with more limited aggregation, suggests that the actin-mediated "down-regulation" may be more prominent in laboratory experiments than under physiological circumstances.
authors.affiliation: Section on Chemical Immunology, Arthritis and Rheumatism Branch, NIAMS, Bethesda, MD 20892-1820, USA.
authors.forename: Chikako
authors.initials: C
authors.lastname: Torigoe
authors.forename: Jinming
authors.initials: J
authors.lastname: Song
authors.forename: B George
authors.initials: BG
authors.lastname: Barisas
authors.forename: Henry
authors.initials: H
authors.lastname: Metzger
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D000072377:Syk Kinase; D013696:Temperature; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C037067:latrunculin A