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A more recent version of this article appeared on March 1, 2003

Papers In Press, published online ahead of print January 1, 2003
J. Lipid Res., doi:10.1194/jlr.M200296-JLR200
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Submitted on July 26, 2002
Revised on December 18, 2002
Accepted on December 20, 2002

Alkylacylglycerolipid domain of Glycosylphosphatidylinositol (GPI) molecules of Leishmania is responsible for inhibition of protein kinase C mediated c-fos gene expression in macrophages

Mamta Chawla and Ram A. Vishwakarma

Bio-organic Chemistry Lab, National Institute of Immunology, New Delhi 110067

Corresponding Author: ram{at}nii.res.in

Glycosylphosphatidylinositols (GPIs) are the most abundant molecules present in the membranes of the parasitic protozoa Leishmania, responsible for multiple forms of leishmaniasis. Among the prominent biological activity displayed by the major Leishmania GPIs (LPG and GIPLs) is the inhibition of macrophage functions such as PKC dependent signaling pathway. The bioactivity of Leishmania GPIs is in contrast to Trypanosoma brucei and Plasmodium falciparum GPIs, which activate the macrophage functions. To address the question as to which structural domain of Leishmania GPIs is responsible for dramatic down-regulation of PKC dependent transient c-fos expression, chemically synthesized defined alkylacylglycerolipids domain of corresponding GPIs, and LPG and GIPLs isolated from L. donovani, were evaluated for inhibition of PKC and c-fos expression in macrophages. The results presented here demonstrate that the unusual lipid domain of Leishmania GPIs is primarily responsible for inhibition of PKC dependent transient c-fos expression


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J. Biol. Chem.Home page
R. Zufferey, S. Allen, T. Barron, D. R. Sullivan, P. W. Denny, I. C. Almeida, D. F. Smith, S. J. Turco, M. A. J. Ferguson, and S. M. Beverley
Ether Phospholipids and Glycosylinositolphospholipids Are Not Required for Amastigote Virulence or for Inhibition of Macrophage Activation by Leishmania major
J. Biol. Chem., November 7, 2003; 278(45): 44708 - 44718.
[Abstract] [Full Text] [PDF]




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