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

Authors :
Heyu Ni
Susan E. Quaggin
Nunzio Bottini
Huong Huynh
Tomas Mustelin
Jinyi Zhang
Joshua Kruger
Kan Saito
Jun Li
Colin McKerlie
Katherine A. Siminovitch
Vera Cherepanov
Patrick Shannon
Yingchun Wang
Eric Vachon
Philip A. Marsden
Hong Yang
Zhizhuang Joe Zhao
Gregory P. Downey
Source :
The Journal of Experimental Medicine
Publication Year :
2005
Publisher :
Rockefeller University Press, 2005.

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.

Details

ISSN :
15409538 and 00221007
Volume :
202
Database :
OpenAIRE
Journal :
Journal of Experimental Medicine
Accession number :
edsair.doi.dedup.....fb9fcadb14abbdd12ee4fdebda24563e
Full Text :
https://doi.org/10.1084/jem.20051108