MAST CELL-RESTRICTED p70 STAT6 ISOFORM IS A PRODUCT OF SELECTIVE PROTEOLYSIS

Shelburne, Christopher P.; Piekorz, Roland P.; Bouton, L.Andrew; Chong, Hey; Ryan, John

doi:10.1006/cyto.2002.1957

Cited by 13 publications

(9 citation statements)

References 44 publications

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“…Western blotting was performed using 29 g of total cellular protein as described previously (30). For immunoprecipitation and Western blotting of Fc⑀RI ␣, cells (3 ϫ 10 5 cells/ml) were cultured in the indicated culture conditions for 4 days, resuspended in cRPMI, pelleted, and solubilized in lysis buffer (0.5% Nonidet P-40, 10% glycerol; 5 M NaCl; 100 mM Tris; 100 mM MgCl 2 ; supplemented with an enhanced inhibitor mixture consisting of a 20ϫ concentrate of Complete, with 80 mM benzamidine HCL, 50 mM ⑀-caproic acid, 16 mM iodoacetamide, 10 g/ml leupeptin, 10 g/ml pepstatin, and 100 g/ml soybean trypsin inhibitor) for 1 h at 4°C.…”

Section: Western Blot Analysismentioning

confidence: 99%

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

Gillespie

DeMartino

Zhu

et al. 2004

The Journal of Immunology

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FcεRI expression and function is a central aspect of allergic disease. Using bone marrow-derived mouse mast cell populations, we have previously shown that the Th2 cytokine IL-4 inhibits FcεRI expression and function. In the current study we show that the Th2 cytokine IL-10 has similar regulatory properties, and that it augments the inhibitory effects of IL-4. FcεRI down-regulation was functionally significant, as it diminished inflammatory cytokine production and IgE-mediated FcεRI up-regulation. IL-10 and IL-4 reduced FcεRI β protein expression without altering the α or γ subunits. The ability of IL-4 and IL-10 to alter FcεRI expression by targeting the β-chain, a critical receptor subunit known to modulate receptor expression and signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network that could serve to both initiate and limit mast cell effector function.

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Section: Western Blot Analysismentioning

confidence: 99%

IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

Gillespie

DeMartino

Zhu

et al. 2004

The Journal of Immunology

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“…A number of studies have reported a 65 000-70 000 MW mast cell-specific isoform of STAT6 and have demonstrated it to be a result of proteolytic processing by a nuclear serine protease. 35,36,50,51 Although processing of STAT6 to this shorter isoform is thought to act as a repressor forming part of a negative feedback loop, 35,51 phosphorylation of STAT6 occurs in the cytoplasm before translocation to the nucleus. 52 Thus our data are consistent with HgCl 2 inducing phosphorylation of STAT6 prior to translocation to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Characterization of cis‐regulatory elements conferring mercury‐induced interleukin‐4 gene expression in rat mast cells: a role for signal transducer and activator of transcription 6 and TATA box binding sites

Pearson

Oliveira

2009

Immunology

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Summary We have previously shown that oxidative stress is involved in the pathogenesis of a mercuric chloride (HgCl2)‐induced, T helper type 2 (Th2)‐driven autoimmune syndrome in Brown Norway (BN) rats. In the context of the syndrome, the oxidative stress‐induced mast cell response seems to determine the development of the early phase of vasculitis, while oxidative stress‐mediated interleukin (IL)‐4 production may contribute to the subsequent Th2‐driven autoimmune response. However, the molecular basis of IL‐4 gene transcription induced by HgCl2 in mast cells remains unknown. In the present study, we dissect the critical regulatory mechanisms in the IL‐4 gene promoter in the rat mast cell line RBL‐2H3. Immunoprecipitation provided evidence that treatment with HgCl2 increased phosphorylation of signal transducer and activator of transcription 6 (STAT6). Transient transfection reporter analyses with a series of 5′ end deletions of the IL‐4 promoter produced evidence that STAT6 and TATA box binding sites are important in HgCl2‐induced IL‐4 gene expression. Subsequent elimination of one or both sites by site‐directed mutagenesis significantly inhibited IL‐4 promoter activity. Our results provide evidence that STAT6 and TATA box regulatory elements play an important role in HgCl2‐induced IL‐4 transcription in rat mast cells.

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“…Isoforms of STAT3, STAT5, and STAT6 generated by proteolysis have been reported. [98][99][100][101][102] These isoforms are referred as STATg, whereas the isoforms generated by pre-mRNA alternative splicing are referred as STATb. STATb isoforms have been found for STAT1, STAT3, STAT4, and STAT5.…”

Section: Stat Trafficking Determines Cytokine Sensitivity and Responsesmentioning

confidence: 99%