Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function

摘要: MEG2, a protein tyrosine phosphatase with unique NH2-terminal lipid-binding domain, binds to and is modulated by the polyphosphoinositides PI(4,5)P2 PI(3,4,5)P3. Recent data implicate MEG2 in vesicle fusion events leukocytes. Through genesis of Meg2-deficient mice, we demonstrate that Meg2 − / embryos manifest hemorrhages, neural tube defects including exencephaly meningomyeloceles, cerebral infarctions, abnormal bone development, >90% late embryonic lethality. T lymphocytes platelets isolated from recombination activating gene 2 mice transplanted liver–derived hematopoietic progenitor cells showed profound activation that, lymphocytes, was attributable impaired interleukin secretion. Ultrastructural analysis these revealed near complete absence mature secretory vesicles. Taken together, observations suggest MEG2-mediated modulation function plays an essential role tube, vascular, development as well lymphocytes.