Specificity in signal transduction among glycosylphosphatidylinositols of Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.
Glycosylphosphatidylinositols (GPIs) and related glycoconjugates of parasite origin have been shown to regulate both the innate and acquired immune systems of the host. This is achieved through the activation of novel GPI-dependent signalling pathways in macrophages, lymphocytes and other cell types. Parasite GPIs impart at least two distinct signals to host cells through the structurally distinct inositolphosphoglycan (IPG) and fatty acid domains. Binding of IPG to as yet uncharacterized cell surface receptor(s) leads to activation of src-family protein tyrosine kinases: depending upon structure, GPI-derived fatty acids can either activate or antagonize protein kinase C, and may enter the sphingomyelinase pathway. The degree of fatty acid saturation may also contribute to signalling activity. Thus, variation in structure of parasite GPIs imparts different properties of signal transduction upon this class of glycolipid. The divergent activities of GPIs from various protozoal taxa reflect global aspects of the host/parasite relationship, suggesting that GPI signalling is a central determinant of disease in malaria, leishmaniasis and both American and African trypanosomiases.
Tachado
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SD
The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Parkville 3050 Victoria, Australia.
Mazhari-Tabrizi
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R
Schofield
L
L
D000818:Animals; D002518:Ceramides / Q000032:analysis; D005227:Fatty Acids / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates; D007891:Leishmania / Q000276:immunology*; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology*; D011134:Polysaccharides; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013045:Species Specificity; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D002518:Ceramides; D005227:Fatty Acids; D017261:Glycosylphosphatidylinositols; D007295:Inositol Phosphates; D009844:Oligosaccharides; D011134:Polysaccharides; C028039:inositol phosphate glycan; D011493:Protein Kinase C