TY - JOUR
T1 - Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function
AU - Wang, Yingchun
AU - Vachon, Eric
AU - Zhang, Jinyi
AU - Cherepanov, Vera
AU - Kruger, Joshua
AU - Li, Jun
AU - Saito, Kan
AU - Shannon, Patrick
AU - Bottini, Nunzio
AU - Huynh, Huong
AU - Ni, Heyu
AU - Yang, Hong
AU - McKerlie, Colin
AU - Quaggin, Sue
AU - Zhizhuang, Joe Zhao
AU - Marsden, Philip A.
AU - Mustelin, Tomas
AU - Siminovitch, Katherine A.
AU - Downey, Gregory P.
PY - 2005/12/5
Y1 - 2005/12/5
N2 - 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. JEM
AB - 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. JEM
UR - http://www.scopus.com/inward/record.url?scp=28544437137&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28544437137&partnerID=8YFLogxK
U2 - 10.1084/jem.20051108
DO - 10.1084/jem.20051108
M3 - Article
C2 - 16330817
AN - SCOPUS:28544437137
SN - 0022-1007
VL - 202
SP - 1587
EP - 1597
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 11
ER -