title: The transcription factor Zeb2 regulates signaling in mast cells.
abstract: Mast cell activation results in the release of stored and newly synthesized inflammatory mediators. We found that Zeb2 (also named Sip1, Zfhx1b), a zinc finger transcription factor, regulates both early and late mast cell responses. Transfection with small interfering RNA (siRNA) reduced Zeb2 expression and resulted in decreased FcεRI-mediated degranulation, with a parallel reduction in receptor-induced activation of NFAT and NF-κB transcription factors, but an enhanced response to the LPS-mediated activation of NF-κB. There was variable and less of a decrease in the Ag-mediated release of the cytokines TNF-α, IL-13, and CCL-4. This suggests that low Zeb2 expression differentially regulates signaling pathways in mast cells. Multiple phosphorylation events were impaired that affected molecules both at early and late events in the signaling pathway. The Zeb2 siRNA-treated mast cells had altered cell cycle progression, as well as decreased expression of several molecules including cell surface FcεRI and its β subunit, Gab2, phospholipase-Cγ1, and phospholipase-Cγ2, all of which are required for receptor-induced signal transduction. The results indicate that the transcription factor Zeb2 controls the expression of molecules thereby regulating signaling in mast cells.
authors.affiliation: Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Emilia Alina
authors.initials: EA
authors.lastname: Barbu
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.forename: Elsa H
authors.initials: EH
authors.lastname: Berenstein
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Groves
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Parks
authors.forename: Reuben P
authors.initials: RP
authors.lastname: Siraganian
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000276:immunology* / Q000378:metabolism*; D015151:Immunoblotting; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2