title: Diacylglycerol kinase γ regulates antigen-induced mast cell degranulation by mediating Ca(2+) influxes.
abstract: Diacylglycerol (DAG) is an important lipid that acts as a signaling messenger during mast cell degranulation after allergen cross-linking of immunoglobulin (Ig) E-bound FcεRI receptors. In this study, we determined the role of diacylglycerol kinase (DGK), which negatively regulates DAG-dependent signaling by converting DAG to phosphatidic acid (PA), in the regulation of mast cell degranulation. Treating RBL (rat basophilic leukemia)-2H3 mast cells with a type I DGK inhibitor significantly reduced antigen-induced degranulation and PA production. Among type I DGK isoforms, we observed that DGKα and DGKγ mRNAs were expressed in RBL-2H3 mast cells using reverse transcription polymerase chain reaction. DGKγ knockdown, but not DGKα, by isoform-specific short hairpin RNAs reduced mast cell degranulation and Ca(2+) influxes from the extracellular environment. These results suggest that DGKγ regulates mast cell degranulation after FcεRI cross-linking through mobilization of intracellular Ca(2+) through Ca(2+) influxes.
authors: Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
authors: Megumi
authors: M
authors: Sakuma
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan.
authors: Yasuhito
authors: Y
authors: Shirai
authors: Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
authors: Takehiko
authors: T
authors: Ueyama
authors: Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan. Electronic address: naosaito@kobe-u.ac.jp.
authors: Naoaki
authors: N
authors: Saito
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D002118:Calcium / Q000276:immunology*; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D051381:Rats
chemical_list: D000941:Antigens; D020033:Protein Isoforms; D019852:Diacylglycerol Kinase; D002118:Calcium
keywords: Ca(2+) influxes; Degranulation; Diacylglycerol kinase (DGK); Mast cell