Cooperation between the Fc epsilonR1 and formyl peptide receptor signaling pathways in RBL(FPR) cells: the contribution of receptor-specific Ca2+ mobilization responses.
RBL(FPR) mast cells express the tyrosine kinase-coupled IgE receptor, Fc epsilonR1, and the G-protein-coupled formyl peptide receptor, FPR. Fc epsilonR1 crosslinking causes Ca2+ stores release, Ca2+ influx, Ins(1,4,5)P3 production and secretion. FPR ligation also mobilizes Ca2+, but without measurable Ins(1,4,5)P3 production or secretion. Co-stimulating the FPR and Fc epsilonR1 induces more Ins(1,4,5)P3 production and secretion than Fc epsilonR1 cross-linking alone. Costimulation also produces more rapid and sustained Ca2+ responses than are generated by Fc epsilonR1 activation alone. We identified multiple differences between the FPR- and Fc epsilonR1-coupled Ca2+ responses, including a more rapid Ca2+ spike response to FPR ligation; intracellular Ca2+ stores that are empty following Fc epsilonR1 crosslinking but partially full following FPR activation; a more sustained Ca2+ influx response to Fc epsilonR1 crosslinking; and the immediate inhibition of stimulated Ca2+ influx by FPR antagonists but not by monovalent ligand that terminates Fc epsilonR1 crosslinking. We hypothesize that the interaction of receptor-specific Ca2+ mobilization pathways contributes to the FPR-mediated potentiation of Fc epsilonR1-coupled secretion.
Lee
R J
RJ
Department of Pathology and Cancer Research & Treatment Center, University of New Mexico Health Sciences Center, Albuquerque 87131, USA.
Lujan
D E
DE
Hall
A L
AL
Sklar
L A
LA
Wilson
B S
BS
Oliver
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004140:Dinitrophenols / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D017455:Receptors, IgE / Q000096:biosynthesis / Q000502:physiology*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D004140:Dinitrophenols; D044042:Receptors, Formyl Peptide; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D020794:Receptor Protein-Tyrosine Kinases; D002118:Calcium