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Involvement of Protein Tyrosine Kinases and Phosphatases in Uptake and Intracellular Replication of Virulent and Avirulent Leishmania donovani Promastigotes in Mouse Macrophage Cells

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Title Involvement of Protein Tyrosine Kinases and Phosphatases
in Uptake and Intracellular Replication of Virulent and
Avirulent Leishmania donovani Promastigotes
in Mouse Macrophage Cells
 
Creator Ghosh, Debjani
Chakraborty, Prasanta
 
Subject Drug Development/Diagnostics & Biotechnology
Infectious Diseases and Immunology
 
Description In this study we show that protein tyrosine kinases (PTKs) and also protein tyrosine
phosphatases are involved in the uptake of virulent and avirulent Leishmania donoûani
promastigotes by macrophage cells. Protein tyrosine kinase inhibitors such as genistein or
tyrphostin 25 decrease parasite uptake in a dose-dependent manner. Addition of sodium
orthovanadate, a protein tyrosine phosphatase inhibitor, prior to infection significantly
increases parasite internalization. A similar uptake profile was observed with both virulent
and avirulent L. donoûani promastigotes. Treatment of macrophages with cytochalasin B,
an inhibitor of actin polymerization prevents promastigote uptake, indicating that a tyrosine
kinase induced actin polymerization signal may be necessary for the entry of the parasites.
In contrast, neither genistein nor tyrphostin significantly reduce intracellular
replication of this pathogen or nitric oxide production, suggesting that the PTK-mediated
signal is not related to the ultimate virulence mechanism associated with intracellular replication
of this pathogen. These data collectively suggest that protein tyrosine kinase
mediated entry of L. donoûani promastigotes into macrophages is not a virulence-associated
event.
 
Publisher Kluwer
 
Date 2002
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/749/1/BIOSCIENCE_REPORTS__22(_3%2D4)_395%2D406;2002[37].pdf
Ghosh, Debjani and Chakraborty, Prasanta (2002) Involvement of Protein Tyrosine Kinases and Phosphatases in Uptake and Intracellular Replication of Virulent and Avirulent Leishmania donovani Promastigotes in Mouse Macrophage Cells. Bioscience Reports, 22 (3-4). pp. 395-406.
 
Relation http://dx.doi.org/ 10.1023/A:1020914024544
http://www.eprints.iicb.res.in/749/