Regulation of interleukin 3 mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions.

Wodnar-Filipowicz, Aleksandra; Moroni, Christoph

doi:10.1073/pnas.87.2.777

Cited by 147 publications

(78 citation statements)

References 38 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that Fc⑀R-mediated elevation of [Ca 2ϩ ] i is required for cytokine production at transcriptional levels (46,47). An increase in intracellular Ca 2ϩ concentration activates protein phosphatase calcineurin, leading to nuclear translocation of the transcription factor NFAT (48,49).…”

Section: Plc␥2-deficient Mast Cells Have Impaired Degranulation But mentioning

confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

Phospholipase Cγ2 (PLCγ2) plays a critical role in the functions of the B cell receptor in B cells and of the FcRγ chain-containing collagen receptor in platelets. Here we report that PLCγ2 is also expressed in mast cells and monocytes/macrophages and is activated by cross-linking of FcεR and FcγR. Although PLCγ2-deficient mice have normal development and numbers of mast cells and monocytes/macrophages, we demonstrate that PLCγ2 is essential for specific functions of FcεR and FcγR. While PLCγ2-deficient mast cells have normal mitogen-activated protein kinase activation and cytokine production at mRNA levels, the mutant cells have impaired FcεR-mediated Ca2+ flux and inositol 1,4,5-trisphosphate production, degranulation, and cytokine secretion. As a physiological consequence of the effect of PLCγ2 deficiency, the mutant mice are resistant to IgE-mediated cutaneous inflammatory skin reaction. Macrophages from PLCγ2-deficient mice have no detectable FcγR-mediated Ca2+ flux; however, the mutant cells have normal FcγR-mediated phagocytosis. Moreover, PLCγ2 plays a nonredundant role in FcγR-mediated inflammatory skin reaction.

show abstract

Section: Plc␥2-deficient Mast Cells Have Impaired Degranulation But mentioning

confidence: 99%

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Wen

Jou

Chen

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…However, in only a few instances have the AU-rich sequences been shown to function effectively as determinants of decay, and in these cases the features of the AREs that are critical for their function have not been well defined (2,17,22,24,35,37,44,51,54). Because the key features of AREs that contribute to their efficacy as instability determinants are not known, it has been difficult to predict if a particular AU-rich sequence that is present within the 3Ј UTR of an mRNA actually functions as an mRNA-destabilizing sequence.…”

mentioning

confidence: 99%

The Nonamer UUAUUUAUU Is the Key AU-Rich Sequence Motif That Mediates mRNA Degradation

Zubiaga

Belasco

Greenberg

1995

Molecular and Cellular Biology

491

371

View full text Add to dashboard Cite

Labile mRNAs that encode cytokine and immediate-early gene products often contain AU-rich sequences within their 3 untranslated region (UTR). These AU-rich sequences appear to be key determinants of the short half-lives of these mRNAs, although the sequence features of these elements and the mechanism by which they target mRNAs for rapid decay have not been fully defined. We have examined the features of AU-rich elements (AREs) that are crucial for their function as determinants of mRNA instability in mammalian cells by testing the ability of various mutant c-fos AREs and synthetic AREs to direct rapid mRNA deadenylation and decay when inserted within the 3 UTR of the normally stable ␤-globin mRNA. Evidence is presented that the pentamer AUUUA, which previously was suggested to be the minimal determinant of instability present in mammalian AREs, cannot direct rapid mRNA deadenylation and decay. Instead, the nonamer UUAUUUAUU is the elemental AU-rich sequence motif that destabilizes mRNA. Removal of one uridine residue from either end of the nonamer (UUAUUUAU or UAUUUAUU) results in a decrease of potency of the element, while removal of a uridine residue from both ends of the nonamer (UAUUUAU) eliminates detectable destabilizing activity. The inclusion of an additional uridine residue at both ends of the nonamer (UUUAUUUAUUU) does not further increase the efficacy of the element. Taken together, these findings suggest that the nonamer UUAUUUAUU is the minimal AU-rich motif that effectively destabilizes mRNA. Additional ARE potency is achieved by combining multiple copies of this nonamer in a single mRNA 3 UTR. Furthermore, analysis of poly(A) shortening rates for ARE-containing mRNAs reveals that the UUAUUUAUU sequence also accelerates mRNA deadenylation and suggests that the UUAUUUAUU motif targets mRNA for rapid deadenylation as an early step in the mRNA decay process.

show abstract

“…Furthermore, several groups have recently identified a number of mRNA-binding proteins with AU specificity (5-10), two of which have been cloned (11,12). Physiological calcium-dependent interleukin 3 (IL-3) production during IgE-triggered mast cell activation involves mRNA stabilization (13,14), and tumors derived from v-Hras-expressing mast cells were found to have a defect in IL-3 mRNA degradation (15,16). Such IL-3 transcripts could be destabilized by cyclosporin A through a mechanism depending on an intact ARE (16).…”

mentioning

confidence: 99%

AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity.

Nakagawa

Waldner²,

Meyer-Monard³

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

127

122

View full text Add to dashboard Cite

AU-rich elements within the 3' untranslated region of transcripts of lymphokines and some protooncogenes serve as signal for rapid mRNA degradation. By using an AUUUA matrix, we have affinity-purified a 32-kDa protein, microsequenced it, and cloned the corresponding cDNA. In vitro, the recombinant protein bound specifically to AU-rich transcripts, including those for interleukin 3, granulocyte/macrophage colony-stimulating factor, c-fos, and c-myc. Sequence analysis revealed an unexpected homology to enoylCoA hydratase (EC 4.2.1.17), and the recombinant protein showed a low degree of the enzymatic activity. Thus, this gene, designated AUH, encodes an RNA binding protein with intrinsic enzymatic activity. Protein immobilized on an AUUUA matrix was enzymatically active, suggesting that hydratase and AU-binding functions are located on distinct domains within a single polypeptide.

show abstract

Regulation of interleukin 3 mRNA expression in mast cells occurs at the posttranscriptional level and is mediated by calcium ions.

Abstract: Interleukin 3

Cited by 147 publications

References 38 publications

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

The Nonamer UUAUUUAUU Is the Key AU-Rich Sequence Motif That Mediates mRNA Degradation

AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity.

Contact Info

Product

Resources

About