gp49B1 inhibits IgE-initiated mast cell activation through both immunoreceptor tyrosine-based inhibitory motifs, recruitment of src homology 2 domain-containing phosphatase-1, and suppression of early and late calcium mobilization
| Autor: | Jennifer M. Lu-Kuo, D M Joyal, Howard R. Katz, K F Austen |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
SH2 Domain-Containing Protein Tyrosine Phosphatases
Molecular Sequence Data Fc receptor chemical and pharmacologic phenomena Bone Marrow Cells Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein tyrosine phosphatase Biochemistry Exocytosis src Homology Domains chemistry.chemical_compound Mice Protein Phosphatase 1 Immunoreceptor tyrosine-based activation motif Animals Amino Acid Sequence Mast Cells Tyrosine Receptors Immunologic Molecular Biology Cells Cultured Mice Inbred BALB C Binding Sites Membrane Glycoproteins biology Sequence Homology Amino Acid Receptors IgE Protein Tyrosine Phosphatase Non-Receptor Type 6 Intracellular Signaling Peptides and Proteins hemic and immune systems Tyrosine phosphorylation Cell Biology Immunoglobulin E Molecular biology chemistry Antigens Surface biology.protein Mutagenesis Site-Directed Calcium Protein Tyrosine Phosphatases Immunoreceptor tyrosine-based inhibitory motif Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | The Journal of biological chemistry. 274(9) |
| ISSN: | 0021-9258 |
| Popis: | We define by molecular, pharmacologic, and physiologic approaches the proximal mechanism by which the immunoglobulin superfamily member gp49B1 inhibits mast cell activation mediated by the high affinity Fc receptor for IgE (FcepsilonRI). In rat basophilic leukemia-2H3 cells expressing transfected mouse gp49B1, mutation of tyrosine to phenylalanine in either of the two immunoreceptor tyrosine-based inhibitory motifs of the gp49B1 cytoplasmic domain partially suppressed gp49B1-mediated inhibition of exocytosis, whereas mutation of both abolished inhibitory capacity. Sodium pervanadate elicited tyrosine phosphorylation of native gp49B1 and association of the tyrosine phosphatases src homology 2 domain-containing phosphatase-1 (SHP-1) and SHP-2 in mouse bone marrow-derived mast cells (mBMMCs). SHP-1 associated transiently with gp49B1 within 1 min after coligation of gp49B1 with cross-linked FcepsilonRI in mBMMCs. SHP-1-deficient mBMMCs exhibited a partial loss of gp49B1-mediated inhibition of FcepsilonRI-induced exocytosis at concentrations of IgE providing optimal exocytosis, revealing a central, but not exclusive, SHP-1 requirement in the counter-regulatory pathway. Coligation of gp49B1 with cross-linked FcepsilonRI on mBMMCs inhibited early release of calcium from intracellular stores and subsequent influx of extracellular calcium, consistent with SHP-1 participation. Because exocytosis is complete within 2 min in mBMMCs, our studies establish a role for SHP-1 in the initial counter-regulatory cellular responses whereby gp49B1 immunoreceptor tyrosine-based inhibition motifs rapidly transmit inhibition of FcepsilonRI-mediated exocytosis. |
| Databáze: | OpenAIRE |
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