Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function.
J Exp Med
; 202(11): 1587-97, 2005 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-16330817
ABSTRACT
MEG2, a protein tyrosine phosphatase with a unique NH2-terminal lipid-binding domain, binds to and is modulated by the polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3. Recent data implicate MEG2 in vesicle fusion events in leukocytes. Through the genesis of Meg2-deficient mice, we demonstrate that Meg2-/- embryos manifest hemorrhages, neural tube defects including exencephaly and meningomyeloceles, cerebral infarctions, abnormal bone development, and >90% late embryonic lethality. T lymphocytes and platelets isolated from recombination activating gene 2-/- mice transplanted with Meg2-/- embryonic liver-derived hematopoietic progenitor cells showed profound defects in activation that, in T lymphocytes, was attributable to impaired interleukin 2 secretion. Ultrastructural analysis of these lymphocytes revealed near complete absence of mature secretory vesicles. Taken together, these observations suggest that MEG2-mediated modulation of secretory vesicle genesis and function plays an essential role in neural tube, vascular, and bone development as well as activation of mature platelets and lymphocytes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Ativação Plaquetária
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Proteínas Tirosina Fosfatases
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Desenvolvimento Embrionário
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article