Characterization of protein tyrosine phosphatases expressed by neutrophils.
Published: 2005
Language: eng
Number of pages: 296
Description: Neutrophils, an essential component of the innate immune system, are regulated in part by signaling pathways involving protein tyrosine phosphorylation. While the role of protein tyrosine kinases has been extensively investigated, little is known about the role of protein tyrosine phosphatases (PTP) in modulating neutrophil signaling cascades. Using reverse transcriptase PCR, expression of the protein-tyrosine phosphatases MEG2 and PTP1B was discovered in neutrophils. We determined that MEG2 is predominantly cytosolic with components present in secondary and tertiary granules, and secretory vesicles. MEG2 also associates with nascent phagosomes, and its activity is inhibited after exposure of neutrophils to the particulate stimulant opsonized zymosan. We have also discovered an autoregulatory mechanism for the MEG2 protein that involves inhibition by its noncatalytic domain, and activation by polyphosphoinositide association. In addition to MEG2, we also studied the function of PTP SHP-1 in neutrophils using motheaten mice. The results of these studies revealed that SHP-1 deficiency in neutrophils results in increased oxidant production, surface expression of CD18, and adhesion. Chemotaxis is severely diminished, possibly due to defective deadhesion and/or altered actin assembly. Taken together, these results indicate that MEG2 and SHP-1 play an important role in the regulation of neutrophil microbicidal functions.
Notes: Thesis (Ph.D.)--University of Toronto, 2005.

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Source: Dissertation Abstracts International, Volume: 66-06, Section: B, page: 3050.