title: Association of 3BP2 with SHP-1 regulates SHP-1-mediated production of TNF-α in RBL-2H3 cells.
abstract: Adaptor protein 3BP2, a c-Abl Src homology 3 (SH3) domain-binding protein, is tyrosine phosphorylated and positively regulates mast cell signal transduction after the aggregation of the high affinity IgE receptor (FcεRI). Overexpression of the Src homology 2 (SH2) domain of 3BP2 results in the dramatic suppression of antigen-induced degranulation in rat basophilic leukemia RBL-2H3 cells. Previously, a linker for activation of T cells (LAT) was identified as one of the 3BP2 SH2 domain-binding protein. In this report, to further understand the functions of 3BP2 in FcεRI-mediated activation of mast cell, we explored the protein that associates with the SH2 domain of 3BP2 and found that SH2 domain-containing phosphatase-1 (SHP-1) inducibly interacts with the SH2 domain of 3BP2 after the aggregation of FcεRI. The phosphorylation of Tyr(564)  in the carboxy (C)-terminal tail region of SHP-1 is required for the direct interaction of SHP-1 to the SH2 domain of 3BP2. The expression of the mutant form of SHP-1 which was unable to interact with 3BP2 resulted in the significant reduction in SHP-1-mediated tumor necrosis factor-α (TNF-α) production without any effects on the degranulation in antigen-stimulated RBL-2H3 cells. These findings suggest that 3BP2 directly interacts with Tyr(564) -phosphorylated form of SHP-1 and positively regulates the function of SHP-1 in FcεRI-mediated signaling in mast cells.
authors.affiliation: Division of Microbiology, Department of Pathological Sciences, University of Fukui, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013058:Mass Spectrometry; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000235:genetics* / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000485:Allergens; D000911:Antibodies, Monoclonal; C553474:FCER1A protein, rat; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509250:Ptpn6 protein, rat