A novel FcεRIß-chain truncation regulates human mast cell proliferation and survival.
FASEB J
; 24(10): 4047-57, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20554927
ABSTRACT
Mast cells contribute to allergy through IgE-dependent activation via the high-affinity IgE receptor FcεRI. The role of the FcεRIß chain (MS4A2) in mast cell function is not understood fully, although it serves to amplify FcεRI-dependent signaling. We demonstrate the expression of a novel MS4A2 truncation lacking exon 3 in human mast cells termed MS4A2(trunc). MS4A2(trunc) gene expression was regulated negatively by the mast cell growth factor stem cell factor (SCF), and its expression was not detected in the SCF receptor gain-of-function human mast cell line HMC-1. Unlike MS4A2, MS4A2(trunc) did not traffic to the cytoplasmic membrane but instead was associated with the nuclear membrane. Overexpression of MS4A2(trunc) induced human lung mast cell death and profoundly inhibited HMC-1 cell proliferation by inducing G(2)-phase cell cycle arrest and apoptosis. Thus, we have identified a novel splice variant of MS4A2 that might be important in the regulation of human mast cell proliferation and survival. This finding demonstrates that the MS4A2 gene has multiple roles, extending beyond the regulation of acute allergic responses. By understanding the mechanisms regulating its function, it might be possible to induce its expression in mast cells in vivo, which could lead to better treatments for diseases such as mastocytosis and asthma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sobrevivência Celular
/
Receptores de IgE
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Proliferação de Células
/
Mastócitos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido