Lyn dissociation from phosphorylated FceRI subunits: A new regulatory step in the FceRI signaling cascade revealed by studies of FceRI dimer signaling activity
Por:
Ortega E., Lara M., Lee I., Santana C., Martinez A.M., Pfeiffer J.R., Lee R.J., Wilson B.S., Oliver J.M.
Publicada:
1 ene 1999
Resumen:
Cross-linking the heterotrimeric (???2) IgE receptor, Fc?RI, of mast cells activates two tyrosine kinases: Lyn, which phosphorylates ? and ? subunit immunoreceptor tyrosine-based activation motifs, and Syk, which binds ?-phospho-immunoreceptor tyrosine-based activation motifs and initiates cellular responses. We studied three Fc?RI-dimerizing mAbs that maintain similar dispersed distributions over the surface of RBL-2H3 mast cells but elicit very different signaling responses. Specifically, mAb H10 receptor dimers induce very little inositol 1,4,5-trisphosphate synthesis, Ca2+ mobilization, secretion, spreading, ruffling, and actin plaque assembly, whereas dimers generated with the other anti-Fc?RI mAbs induce responses that are only modestly lower than that to multivalent Ag. H10 receptor dimers activate Lyn and support Fc?RI ? and ? subunit phosphorylation but are poor Syk activators compared with Ag and the other anti-Fc?RI mAbs. H10 receptor dimers have two other distinguishing features. First, they induce stable complexes between activated Lyn and receptor subunits. Second, the predominant Lyn-binding phospho-? isoform found in mAb H10-treated cells is a less tyrosine phosphorylated, more electrophoretically mobile species than the predominant isoform in Ag-treated cells that does not coprecipitate with Lyn. These studies implicate Lyn dissociation from highly phosphorylated receptor subunits as a new regulatory step in the Fc?RI signaling cascade required for Syk activation and signal progression.
Filiaciones:
Ortega E.:
Departamento de Inmunologia, Inst. de Investigaciones Biomedicas, Univ. Nac. Autónoma de Mexico, Mexico City, Mexico
Lara M.:
Departamento de Inmunologia, Inst. de Investigaciones Biomedicas, Univ. Nac. Autónoma de Mexico, Mexico City, Mexico
Lee I.:
Departamento de Inmunologia, Inst. de Investigaciones Biomedicas, Univ. Nac. Autónoma de Mexico, Mexico City, Mexico
Santana C.:
Departamento de Inmunologia, Inst. de Investigaciones Biomedicas, Univ. Nac. Autónoma de Mexico, Mexico City, Mexico
Martinez A.M.:
Department of Pathology, Cancer Research and Treatment Center, Univ. of New Mex. Hlth. Sci. Center, Albuquerque, NM 87131, United States
Pfeiffer J.R.:
Department of Pathology, Cancer Research and Treatment Center, Univ. of New Mex. Hlth. Sci. Center, Albuquerque, NM 87131, United States
Lee R.J.:
Department of Pathology, Cancer Research and Treatment Center, Univ. of New Mex. Hlth. Sci. Center, Albuquerque, NM 87131, United States
Wilson B.S.:
Department of Pathology, Cancer Research and Treatment Center, Univ. of New Mex. Hlth. Sci. Center, Albuquerque, NM 87131, United States
Oliver J.M.:
Department of Pathology, Cancer Research and Treatment Center, Univ. of New Mex. Hlth. Sci. Center, Albuquerque, NM 87131, United States
Cell Pathology Laboratory, Cancer Research Facility, Univ. of New Mex. School of Medicine, 2325 Camino de Salud, Albuquerque, NM 87131, United States
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