title: Signal transduction in host cells mediated by glycosylphosphatidylinositols of the parasitic protozoa, or why do the parasitic protozoa have so many GPI molecules?
abstract: Considerable circumstantial evidence indicates that glycosylphosphatidylinositol (GPI) molecules of mammalian origin are able to mediate signal transduction in lymphoid cells. For example, perturbation of GPI-anchored surface proteins, but not transmembrane forms of these molecules, can lead to the activation of T lymphocytes. GPIs appear also to be precursors of pharmacologically active phosphoinositol-glycans which mediate responses to hormones such as insulin, nerve growth factor and IL-2. Nonetheless, the biochemical mechanisms of signal transduction by GPIs remain obscure. We have shown that structurally defined GPIs of protozoal parasite origin are able to mediate signal transduction in host macrophages and lymphocytes, by substituting for the putative endogenous GPI-based signalling mechanisms of the host. Signalling by parasite GPIs appears to involve the activation of protein tyrosine kinase and protein kinase C. Evidence from other sources indicates that structurally variant GPIs may provide anergic signals to down-regulate host cell function. These phenomena may represent mechanisms by which eukaryotic parasites regulate host cell function, and can explain a variety of pathological and immunological features of protozoal infections. Furthermore, protozoal GPIs may prove to be an informative model system for the analysis of GPI-mediated signal transduction in lymphocytes and macrophages.
authors.affiliation: National Institute for Medical Research, Mill Hill, London, England.
authors.forename: L
authors.initials: L
authors.lastname: Schofield
authors.forename: P
authors.initials: P
authors.lastname: Gerold
authors.forename: R T
authors.initials: RT
authors.lastname: Schwarz
authors.forename: S
authors.initials: S
authors.lastname: Tachado
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology; D056890:Eukaryota / Q000737:chemistry* / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology; D010963:Plasmodium falciparum / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D017261:Glycosylphosphatidylinositols; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C