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Protein-tyrosine phosphatase MEG2 is expressed by human neutrophils. Localization to the phagosome and activation by

Joshua M Kruger1, Takayasu Fukushima, Vera Cherepanov

  • 1Division of Respirology, The Toronto General Hospital Research Institute of the University Health Network, Toronto, Ontario M5S 1A8, Canada.

The Journal of Biological Chemistry
|November 17, 2001
PubMed

Insights

The protein-tyrosine phosphatase MEG2 is crucial for neutrophil antimicrobial responses. Its activity is regulated by polyphosphoinositides and it plays a role in phagocytosis signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Neutrophil antimicrobial responses rely on tyrosine phosphorylation signaling pathways.
  • Protein-tyrosine phosphatases (PTPs) are key regulators of these signaling events.

Purpose of the Study:

  • To identify and characterize the PTP MEG2 in neutrophils.
  • To elucidate the role of MEG2 in neutrophil function and antimicrobial responses.

Main Methods:

  • Reverse transcriptase PCR to detect MEG2 gene expression in polymorphonuclear leukocytes (PMN).
  • Development of polyclonal antibodies to confirm MEG2 protein expression in PMN.
  • Immunofluorescence, cell fractionation, and immunoblotting to determine MEG2 localization.
  • In vitro phosphatase assays and immunoprecipitation to assess MEG2 activity.
  • Studies using bacterially expressed glutathione S-transferase MEG2 fusion protein to identify key functional domains.
  • Investigation of MEG2 interaction with polyphosphoinositides and phagosomes.

Main Results:

  • MEG2 is expressed in human neutrophils (PMN) and is predominantly cytosolic, with presence in granules and vesicles.
  • MEG2 activity is inhibited by particulate stimulants like opsonized zymosan and phorbol 12-myristate 13-acetate.
  • Cysteine 515 is essential for MEG2 catalytic activity, and the N-terminal domain negatively regulates the C-terminal domain.
  • MEG2 activity is enhanced by specific polyphosphoinositides, with PI(4,5)P2 being the most potent activator.
  • MEG2 associates with nascent phagosomes during the early stages of phagocytosis.

Conclusions:

  • MEG2 is a polyphosphoinositide-activated tyrosine phosphatase found in neutrophils.
  • MEG2 likely plays a significant role in the signaling pathways that regulate phagocytosis, a critical component of the innate immune response.

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