Signal transduction in macrophages by glycosylphosphatidylinositols of Plasmodium, Trypanosoma, and Leishmania: Activation of protein tyrosine kinases and protein kinase C by inositolglycan and diacylglycerol moieties

Abstract

The perturbation of various glycosylphosphatidylinositol (GPI)-anchored surface proteins imparts profound regulatory signals to macrophages, lymphocytes and other cell types. The specific contribution of the GPI moieties to these events however is unclear. This study demonstrates that purified GPIs of Plasmodium falciparum, Trypanosoma brucei, and Leishmania mexicana origin are sufficient to initiate signal transduction when added alone to host cells as chemically defined agonists. GPIs (10 nM-1 μM) induce rapid activation of the protein tyrosine kinase (PTK) p59hck in macrophages. The minimal structural requirement for PTK activation is the evolutionarily conserved core glycan sequence Mana..