title: Enhancement of TNF-alpha synthesis by overexpression of G alpha z in a mast cell line.
abstract: Ag stimulation of mast cells via the IgE receptor (Fc epsilon RI) elicits production and release of numerous cytokines. This activation of Fc epsilon RI initiates various tyrosine kinase-dependent signaling cascades, which ultimately result in the de novo synthesis of cytokines. To date, no heterotrimeric G proteins have been implicated in this process. Here we report that the alpha subunit of the heterotrimeric G protein, Gz, can regulate production of the cytokine, TNF-alpha. The alpha subunit was overexpressed in a cultured mast cell line (RBL-2H3) known to contain G alpha z. In stimulated cells, overexpression of G alpha z significantly enhanced the production of TNF-alpha. This effect of G alpha z appeared to be restricted in that constitutive synthesis of the cytokine, TGF-beta, and Ag-stimulation of the phosphoinositide-dependent secretory pathway were not significantly affected. Thus, G alpha z, a heterotrimeric G protein, appeared to modulate the stimulatory pathways for induction of TNF-alpha synthesis in RBL-2H3 cells.
authors: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: R A
authors: RA
authors: Baumgartner
authors: N
authors: N
authors: Hirasawa
authors: K
authors: K
authors: Ozawa
authors: F
authors: F
authors: Gusovsky
authors: M A
authors: MA
authors: Beaven
mesh_terms: D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D015973:Gene Expression Regulation, Leukemic; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018076:DNA, Complementary; C099387:GNAZ protein, human; D044385:GTP-Binding Protein alpha Subunits; C490963:Gnaz protein, rat; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D010716:Phosphatidylinositols; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D003907:Dexamethasone; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins