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

Yingchun Wang, Eric Vachon, Jinyi Zhang, Vera Cherepanov, Joshua Kruger, Jun Li, Kan Saito, Patrick Shannon, Nunzio Bottini, Huong Huynh, Heyu Ni, Hong Yang, Colin McKerlie, Sue Quaggin, Joe Zhao Zhizhuang, Philip A. Marsden, Tomas Mustelin, Katherine A. Siminovitch, Gregory P. Downey*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

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. JEM

Original languageEnglish (US)
Pages (from-to)1587-1597
Number of pages11
JournalJournal of Experimental Medicine
Volume202
Issue number11
DOIs
StatePublished - Dec 5 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, Y., Vachon, E., Zhang, J., Cherepanov, V., Kruger, J., Li, J., Saito, K., Shannon, P., Bottini, N., Huynh, H., Ni, H., Yang, H., McKerlie, C., Quaggin, S., Zhizhuang, J. Z., Marsden, P. A., Mustelin, T., Siminovitch, K. A., & Downey, G. P. (2005). Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function. Journal of Experimental Medicine, 202(11), 1587-1597. https://doi.org/10.1084/jem.20051108