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Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function
- 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.
- Subjects :
- Blood Platelets
Interleukin 2
Vesicle fusion
T-Lymphocytes
Immunology
Embryonic Development
Neovascularization, Physiologic
Hemorrhage
Protein tyrosine phosphatase
Biology
Lymphocyte Activation
Article
Recombination-activating gene
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Immunology and Allergy
Secretion
Neural Tube Defects
Platelet activation
030304 developmental biology
Mice, Knockout
0303 health sciences
Bone Development
Secretory Vesicles
Embryogenesis
Hematopoietic Stem Cell Transplantation
Cerebral Infarction
Hematopoietic Stem Cells
Platelet Activation
Protein Tyrosine Phosphatases, Non-Receptor
Secretory Vesicle
Cell biology
Liver
Biochemistry
030220 oncology & carcinogenesis
Protein Tyrosine Phosphatases
medicine.drug
Subjects
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